Cerebrospinal fluid biomarkers of symptomatic neurosyphilis in people with HIV compared with uninfected individuals

Cerebrospinal fluid biomarkers of symptomatic neurosyphilis in people with HIV compared with uninfected individuals | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cerebrospinal fluid biomarkers of symptomatic neurosyphilis in people with HIV compared with uninfected individuals Sérgio Monteiro de Almeida, José Tresoldi Neto, Amanda Rocha, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3673645/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n=42), presumptive NS (n=74), systemic syphilis (SS) (n=38), serological diagnosis of syphilis (n=18), PWH without SS and NS (n=10), and negative control (n=72). In PWoH, for presumptive NS, the combination of CSF TP >45 mg/dL and/or WBC >5.0 cells/mm 3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS. In PWoH, the value of CSF TP >45 mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count >20 cell/mm 3 , the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of >10 or >20 cells/mm 3 , was moderately applicable for screening. As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, being better in the former. However, these biomarkers could be included for presumptive NS diagnosis. Additionally, the DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection. neurosyphilis central nervous system cerebrospinal fluid diagnosis HIV Figures Figure 1 Figure 2 Figure 3 Figure 4 1. INTRODUCTION Neurosyphilis (NS) diagnosis remains challenging as no gold standard tests are available [Guarner et al. 2015; Yu et al. 2021]. A reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test confirms the diagnosis of NS in a patient with a reactive serum treponemal test. However, a nonreactive test cannot exclude NS diagnosis. Combining nontreponemal assays with the analysis of CSF characteristics improves NS diagnostic accuracy [Dumaresq et al. 2013; Salamano et al. 2016]. CSF-VDRL has more false positives and negatives in people with HIV (PWH) [Feraru et al. 1990]; therefore, diagnosis of NS in PWH may additionally require the identification of increased CSF white blood cell (WBC) count and CSF total protein (TP). This study aimed to expand on previous studies by measuring the diagnostic clinical performance characteristics (DCPC) of CSF TP, WBC count, and lactate (LA) with different cutoff points as adjunct predictive biomarkers for confirmed or presumptive symptomatic NS, and the impact of HIV infection on them. 2. METHODS 2.1 Study design and participants This was a retrospective analysis of medical reports and laboratory data collected from electronic medical charts of the Hospital de Clínicas, Universidade Federal do Paraná (HC-UFPR), Curitiba, Paraná, Brazil. All CSF samples included in this study were collected for clinical purpose via lumbar puncture (LP), between December 2005 and August 2021. 5,640 CSF reports, all with Rapid Plasm Reagin (RPR) assay analyzed in CSF, were obtained. The flow chart for participant selection is showed in Fig. 1 . The 236 participants included were classified as PWH or people without HIV (PWoH) [Ministério da Saúde 2018]. They were further classified into five subgroups according to the diagnosis of systemic syphilis (SS) [Ministério da Saúde 2011; Ministério da Saúde 2022] and NS [Wharton et al. 1990; French et al. 2009; Workowski and Bolan 2015] (Fig. 1 ): - G.1 Confirmed NS (n = 42): positive CSF RPR [Zhu et al. 2014; Boog et al. 2021], serological diagnosis of SS positive, and neurological symptoms suggestive of NS [Gonzalez et al. 2019; Marra 2015; Ropper 2019]. - G.2 Presumptive NS (n = 74): negative CSF RPR, serological diagnosis of SS positive, and neurological symptoms suggestive of NS, without an alternate diagnosis to account for these. - G.3 SS (n = 38), serological diagnosis of SS, absence of neurological symptoms suggestive of NS, and negative CSF RPR. - G.4 PWH without SS and NS (n = 10), positive HIV diagnosis [Ministério da Saúde 2018], absence of CNS opportunistic infection defined by negative CSF standard microbiological methods and medical history, absence of SS and NS. - G.5 Negative control (n = 72), HIV negative, SS or NS investigation negative, no neurological symptoms other than headache, absence of defined or suspected infection. 2.2 CSF and peripheral blood samples Two treponemal assays, FTA-ABS [Larsen et al. 1995] and Chemiluminescent Microparticle Immuno Assay (CMIA), were performed to qualitatively detect antibodies against Treponema pallidum (Alinity i. Abbott, Germany). The nontreponemal antibody assay used was RPR (BRÁS, Laborclin, Brazil). Tests were performed according to the manufacturer’s instructions. CSF TP was quantified using benzethonium chloride, GL in CSF and plasma using hexokinase/G-6-PDH (both from Architect, Abbott, IL, USA), and CSF LA using amperometry (RAPID Point 500, Siemens, New York City, NY, USA) [de Almeida et al. 2020]. Total CSF WBC count was quantified in fresh uncentrifuged CSF in a Fuchs-Rosenthal chamber. Differential WBC counts were performed using standard laboratory methods. Standard microbiological tests were used to examine CSF samples for bacteria, fungi, and viruses [Deisenhammer et al. 2006]. 2.3 Statistical analysis Data are presented as median and interquartile range (IQR) or number (n, %), as appropriate. Categorical variables were compared among the groups using the Chi-square test or Fisher’s exact test. Continuous variables were compared using the Mann-Whitney or Kruskal-Wallis tests for non-parametric data, as appropriate. We estimated the correlation coefficients (r s ) of CSF and serum RPR titer, CSF WBC count, CSF TP, HIV infection characteristics (current age, age at the beginning of the infection, plasma HIV RNA), and cell immunity characteristics (current CD4 + , CD8 + , CD4 + /CD8 + ratio) using Spearman’s rank-order method. The results were considered significant at 5% alpha level. 2.4 Diagnostic Clinical Performance Characteristics (DCPC) The DCPC of CSF TP and/or WBC count (index tests) for the diagnosis of NS was calculated using confirmed or presumptive NS defined by positive CSF RPR and the presence of clinical characteristics [Wharton et al. 1990] as the reference gold standard method. The DCPC included sensitivity, specificity, accuracy (efficiency), positive and negative predictive values (PPV and NPV), Youden index, positive and negative clinical utility index (CUI + and CUI−) [Mitchell 2008; Mitchell 2011], positive and negative likelihood ratios (LR + and LR−), diagnostic odds ratio (DOR) [Akobeng 2007a; Glas et al. 2003; McGee 2002], Matthews correlation coefficient (MCC) [Matthews 1975]. The post-test probabilities were calculated using Bayes’ theorem, with pre-test probabilities and likelihood ratios plotted on Fagan's nomogram [Sackett and Haynes 2002; TJ 1975]. The receiver operating characteristic (ROC) curve was used to determine the cutoff value associated with the highest distinction between confirmed and/or presumptive NS (G1 and/or G2, respectively) and each of the other categories, including negative controls (G3, G4, and G5). The Youden index (J) was defined for all points in the ROC curve. The maximum value of the index was used as a criterion to select the optimal cut-off point of a diagnostic test, the area under the ROC curve (AUC) was analyzed, and the difference between the curve and the baseline (random line) was calculated [Akobeng 2007a; Akobeng 2007b]. 3. RESULTS The epidemiological, CSF characteristics of the samples distributed according to PWH and PWoH groups, clinical signs and symptoms are presented in Tables 1 and 2 . Among PWH, the groups confirmed NS, presumptive NS, SS, and PWH without SS and/or NS were comparable for PB HIV RNA (log), PB CD4 + lymphocytes (cells/mm³), PB CD8 + lymphocytes (cells/mm³), PB CD4 + /CD8 + , and participants on antiretroviral therapy (ART) (all p > 0.05, Table 1 ). Among PWH with confirmed and presumptive NS, PB HIV RNA levels were higher and PB CD4 + counts were lower than those in the PWH without SS and NS groups (G4). Table 1 Demographic, HIV infection characteristics, and CSF biochemical and cytological characteristics of the samples distributed in the groups PWH and PWoH PWH PWoH PWH PWoH Group A-G1 B-G2 C-G3 D-G4 E-G1 F-G2 G-G3 H-G5 p a p b N 22 16 17 10 20 58 21 72 - - Male, n (%) 17.00 (77.27) 13.00 (81.25) 13 (76.47) 5.00 (50.00) 15.00 (75.00) 33.00 (56.90) 10.00 (47.62) 24.00 (33.33) 0.3089 0.0031 Age, years 42.00 (35.00; 48.75) 40.00 (36.00; 43.00) 49.00 (32.00; 58.50) 40.00 (34.00; 49.25) 55.00 (50.50; 63.00) 67.00 (52.00; 75.75) 62.00 (41.00; 71.50) 49.00 (34.00; 59.50) 0.5024 0.0005 CSF RBC, cells/mm³ 2.25 (0.53; 19.45) 3.90 (0.45; 21.18) 4.10 (0.75; 18.10) 1.00 (0.30; 2.43) 1.70 (0.60; 32.75) 6.85 (0.90; 23.98) 4.00 (0.30; 15.15) 1.80 (0.30; 9.53) 0.2907 0.2145 CSF WBC, cells/mm³ 6.60 (1.28; 30.30) 4.60 (0.90; 6.35) 0.60 (0.30; 1.10) 0.45 (0.23; 1.05) 1.75 (0.38; 12.40) 1.20 (0.60; 2.58) 0.60 (0.30; 1.50) 0.90 (0.30; 1.30) 5 cells/mm³, n (%) 12 (54.54) 6 (37.50) 0 1 (10.00) 5 (25.00) 8 (13.79) 1 (4.76) 2 (2.78) 0.0001 0.0149 Lynphocytes % 95.00 (93.00; 98.00) 91.50 (85.75; 96.25) 0 97.00 95.00 (84.50; 98.00) 91.50 (80.25; 95.00) 93.00 95.00 (95.00; 95.00) 0.2731 0.7028 CSF Glucose, mg/dL 49.00 (38.25; 59.00) 55.50 (46.25; 61.75) 58.00 (50.00; 64.50) 57.00 (48.25; 68.25) 58.50 (53.00; 67.25) 65.50 (58.75; 79.50) 62.00 (53.50; 77.50) 64.50 (57.00; 74.50) 0.0622 0.2808 CSF Total Protein, mg/dL 59.30 (43.83; 84.40) 48.00 (39.63; 65.00) 32.60 (28.20; 40.90) 37.25 (22.85; 62.83) 59.10 (40.43; 68.43) 43.90 (36.05; 54.93) 32.60 (25.00; 38.15) 26.65 (22.40; 33.70) 0.0025 45 mg/dL, n (%) 17 (77.27) 10 (62.50) 3 (17.65) 5 (50.00) 13 (65.00) 28 (48.28) 3 (14.29) 1 (1.39) 0.0024 < 0.0001 CSF Lactate, mmol/L 1.90 (1.56; 2.35) 1.70 (1.40; 2.30) 1.40 (1.30; 1.80) 1.40 (1.33; 1.98) 1.64 (1.52; 2.02) 1.81 (1.60; 2.01) 1.78 (1.64; 2.33) 1.70 (1.50; 1.95) 0.1178 0.3731 HIV RNA, log10 4.60 (3.25; 5.03) 4.82 (3.57; 5.79) 2.79 (1.70; 4.58) 3.90 (1.70; 4.73) - - - - 0.1440 - HIV RNA < 50 copies/mL, n (%) 2/12 (16.67) 1/8 (12.50) 6/14 (42.86) 3/9 (33.33) - - - - 0.3133 - CD4, cells/mm³ 174.00 (38; 320) 135.00 (80.00; 327.80) 192.50 (99.00; 472.30) 121.00 (36.50; 698.50) - - - - 0.7356 - CD4 > 500 cells/mm³, n (%) 0/11 (0) 0/8 (0) 2/12 (16.67) 3/9 (33.33) - - - 0.0906 - CD8. cells/mm³ 877.50 (386.00; 1945.00) 832.00 (67.00; 940.30) 669.00 (386.30; 1094.00) 1057.00 (690.00; 1159.00) - - - - 0.6062 - CD4/CD8 0.15 (0.08; 0.23) 0.20 (0.06; 0.47) 0.28 (0.15; 0.64) 0.11 (0.10; 0.57) - - - - 0.2980 - on ART, n (%) 16/22 (72.73) 10/16 (62.50) 11/17 (64.71) 6/10 (60.00) - - - - - Regular use of ART, n (%) 6/13 (46.15) 6/14 (42.86) 7/12 (58.33) 4/6 (66.67) 0.7995 Data is presented as median (interquartile) or number (n, %) as appropriate. RBC, red blood cell; WBC, white blood cell; PWH, people with HIV; PWoH, people without HIV; ART, antiretroviral therapy; NS, neurosyphilis. G1, confirmed NS; G2, presumptive NS; G3, systemic syphilis; G4, PWH without SS and NS; G5, negative control. p values were calculated with chi-square or Kruskal-Wallis tests as appropriate. a p values for the comparison of the PWH groups, A vs. B vs. C vs. D. b p values for the comparison of the PWoH groups, E vs. F vs. G vs. H. Syphilis infection is known to have a negative impact on immune recovery during HIV infection and an increase in HIV VL in the peripheral blood and CSF [ 31 , 32 , 33 ]. Table 2 Signs and symptoms of participants with confirmed and presumptive NS, in PWH and PWoH. PWH PWoH Signs and Symptoms (n, %) a-G1 b-G2 p a vs. b c-G1 d-G2 p c vs. d p a vs. c p b vs. d Paresis/plegia 7 (31.82) 5 (31.25) 1.00 3 (15.0) 20 (34.49) 1.00 1.00 0.79 Dysarthria/aphasia 4 (18.18) 1 (6.25) 0.36 2 (10.0) 18 (31.03) 1.00 1.00 0.04 Confusion/agitation 3 (13.64) 3 (18.75) 1.00 1 (5.0) 11 (18.97) 1.00 1.00 1.00 spasticity 3 (13.64) 0 0.24 0 2 (3.45) 1.00 0.55 1.00 Neuropsychiatric 1 2 (9.10) 3 (18.75) 0.65 2 (10.0) 8 (13.79) 0.35 0.30 0.72 headache 2 (9.10) 5 (31.25) 0.23 1 (5.0) 5 (8.62) 0.55 1.00 0.05 Hyperreflexia 2 (9.10) 1 (6.25) 1.00 0 0 - 1.00 0.23 Pupillary changes 2 2 (9.10) 0 0.50 0 0 - 1.00 - Paresthesia 2 (9.10) 2 (12.5) 1.00 0 6 (10.35) 1.00 1.00 1.00 ataxic gait 2 (9.10) 1 (6.25) 1.00 0 2 (3.44) 1.00 1.00 0.55 Uveitis 1 (4.05) 1 (6.25) 1.00 2 (10.0) 3 (5.17) 0.11 0.18 1.00 Amaurosis 1 (4.05) 1 (6.25) 1.00 1 (5.0) 3 (5.17) 0.41 0.48 1.00 Nystagmus 1 (4.05) 0 1.00 0 0 - 1.00 - labial commissure deviation 1 (4.05) 1 (6.25) 1.00 0 4 (6.90) 0.11 1.00 1.00 Tremor 3 1 (4.05) 0 1.00 0 2 (3.45) 1.00 1.00 1.00 Diplopia 0 0 - 1 (5.0) 1 (1.72) 0.23 0.28 1.00 Seizure 4 0 3 (18.75) 0.09 0 1 (1.72) 1.00 - 0.04 Papilledema 0 0 - 0 1 (1.72) 1.00 - 1.00 Hypoacusis 0 1 (6.25) 0.46 0 1 (1.72) 1.00 - 0.42 dizziness/vertigo 0 1 (6.25) 0.46 0 6 (10.35) 1.00 - 1.00 Bradykinesia 0 0 - 0 1 (1.72) 1.00 - 1.00 PWH, people with HIV; PWoH, people without HIV; NS, neurosyphilis; G1, confirmed NS; G2, presumptive NS. The participants presented more than one sign or symptom. 1 PWH-G1, memory impairment (n = 2), visual hallucinations (n = 1); PWoH-G1, memory impairment (n = 1), behavior alteration (n = 2); PWH-G2, depression (n = 1), psychosis (n = 1), memory impairment (n = 1); PWoH-G2, dementia (n = 3), personality change (n = 3), delusions (n = 2), depression (n = 1), hallucinations (n = 1), memory impairment (n = 3), psychosis (n = 1). 2 PWH-G1, fixed mydriasis (n = 1), anisocoria (n = 1). 3 PWH-G1, rest tremor (n = 1); PWoH-G2, delirium tremens (n = 1), kinetic and postural tremor (n = 1). 4 PWH-G2, generalized tonic seizures (n = 2), unspecified seizures (n = 1). PWoH-G2, generalized tonic-clonic seizure (n = 1). 3.1 CSF WBC Among PWH, the number of CSF samples with elevated CSF WBC (> 5 cell/mm 3 ) was comparable between the confirmed and presumptive NS groups [12 (55.00%) and 6 (38.00%), respectively, p = 0.342], higher in confirmed NS when compared with the PWH without SS and/or NS group (G4, p = 0.024), and comparable between presumptive NS and G4 (p = 0.19). No increase in CSF WBC count was observed in the SS group (G3). In PWoH, the number of CSF samples with elevated CSF WBC (> 5 cell/mm 3 ) was comparable between the confirmed and presumptive NS and SS groups [5 (25.00), 8 (13.79), and 1 (4.76), respectively, p = 0.176; confirmed vs. presumptive NS groups, p = 0.300]. Higher in the confirmed and presumptive NS groups than in the negative control group (G5) (p = 0.005 and 0.024, respectively), and comparable between the SS and negative control group (G5) (p = 0.540). The number of samples with elevated CSF WBC count was higher in PWH than in PWoH for the confirmed and presumptive NS subgroups, although this difference was not statistically significant (p = 0.066 and 0.065, respectively) and was comparable for the SS groups (p = 1.00). The confirmed NS group had a higher median CSF WBC count, regardless of PHW or PWoH. All comparisons of the confirmed or presumptive NS groups with the negative control group (G5) were p < 0.05 (Table 1 and Fig. 2 ). The median CSF WBC counts were comparable between the confirmed and presumptive NS groups in PWH or PWoH (p = 0.146 and 0.299, respectively). Comparing the confirmed or presumptive NS groups, showed that it was higher in the PWH than in the PWoH [for presumptive NS, p = 0.048; although for confirmed NS, it was not significant (p = 0.078)). The median CSF WBC counts in the SS groups were comparable between PWH and PWoH (p = 0.910) (Table 1 and Fig. 2 ). 3.2 CSF TOTAL PROTEIN Among PWH, the number of CSF samples with CSF TP > 45 mg/dL was comparable among the confirmed and presumptive NS [17 (77.00%) and 10 (66.00%), respectively, p = 0.471] and higher in confirmed and presumptive NS when compared with the SS group (0.0003 and 0.013, respectively). However, both groups were comparable with the G4 group (0.217 and 0.689, respectively). Among PWoH, the number of CSF samples with CSF TP > 45 mg/dL was comparable between confirmed and presumptive NS (p = 0.299), increased in these groups compared with the SS group (p = 0.001 and 0.008), and higher in confirmed NS, presumptive NS, and SS when compared with the negative control group (G5) (ps < 0.0001, < 0.0001, and 0.035, respectively). The confirmed NS group had higher median CSF TP, regardless of PWH or PWoH. All comparisons of the confirmed or presumptive NS groups with the negative control group (G5) were significant (p < 0.05; Table 1 and Fig. 2 ). The median CSF TP was higher in the confirmed or presumptive NS groups in PWoH (p = 0.044) but comparable in PWH (p = 0.193). Comparing the groups between PWH and PWoH, the medians of CSF TP were comparable for confirmed NS, presumptive NS, and SS (P = 0.493, 0.367, 0.063 respectively). Correlations of CSF TP and WBC count with CSF RPR titers in PWoH are shown in Figs. 2 E and F. 3.3 DCPC of CSF WBC count and TP The DCPC of the CSF WBC count single test to diagnose confirmed or presumptive NS in PWH or PWoH is shown in Table 4 . For CSF WBC count, the AUC and MCC were higher in PWH than in PWoH. The higher the cutoff point of CSF WBC, the greater the specificity, LR+, LR-, and the lower the sensitivity. The DOR increases progressively with an increase in the cutoff point, indicating a greater chance of diagnosis. The MCC did not show significant variation between the different cutoff points, indicating that the data compared at each cutoff point had a similar correlation with the others (Table 3 , Fig. 3 ). Table 3 Clinical performance characteristics of CSF WBC count, as single test, with the cutoff points > 5, >10, and > 20 cells/mm³, as adjunct biomarkers to diagnose confirmed and presumptive neurosyphilis in PWH and PWoH. Group Total PWH PWoH CSF WBC (cells/mm³) G1vs.G3 + 4 + 5 G2vs.G3 + 4 + 5 G1 + 2vs.G3 + 4 + 5 G1vs.G3 + 4 G2vs.G3 + 4 G1 + 2vs.G3 + 4 G1vs.G3 + 5 G2vs.G3 + 5 G1 + 2vs.G3 + 5 > 5 cells/mm³ True Positive 17 14 31 12 6 18 5 8 13 Sensitivity, % 40.48 (25.63; 56.72) 18.92 (10.75; 29.70) 26.72 (18.93; 35.74) 54.55 (32.21; 75.61) 37.50 (15.20; 64.57) 47.37 (30.98; 64.18) 25.00 (8.66; 49.10) 13.79 (4.92; 22.67) 16.67 (9.18; 26.81) Specificity, % 96.67 (91.69; 99.08) 96.67 (91.69; 99.08) 96.67 (91.69; 99.08) 96.30 (81.03; 99.91) 96.30 (81.03; 99.91) 96.30 (81.03; 99.91) 97.27 (92.24; 99.43) 97.27 (94.23; 100.00) 97.27 (92.24; 99.43) LR (+) 12.14 (4.33; 34.05) 5.68 (1.94; 16.59) 8.02 (2.92; 22.00) 14.73 (2.07; 104.64) 10.12 (1.34; 76.69) 12.79 (1.82; 90.10) 9.17 (2.38; 35.35) 5.06 (1.39; 18.34) 6.11 (1.80; 20.73) LR (-) 0.62 (0.48; 0.79) 0.84 (0.75; 0.94) 0.76 (0.68; 0.85) 0.47 (0.30; 0.75) 0.65 (0.44; 0.96) 0.55 (0.40; 0.75) 0.77 (0.60; 0.99) 0.89 (0.80; 0.99) 0.86 (0.77; 0.95) DOR 19.72 (6.11; 63.65) 6.77 (2.13; 21.46) 10.58 (3.60; 31.09) 31.20 (3.58; 272.30) 15.60 (1.66; 146.41) 23.40 (2.88; 190.40) 11.89 (2.57; 54.90) 5.71 (1.45; 22.43) 7.13 (1.96; 25.98) CUI+ 0.33 (0.12; 0.54) 0.15 (0.00; 0.32) 0.24 (0.10; 0.37) 0.50 (0.25; 0.76) 0.32 (0; 0.67) 0.45 (0.25; 0.65) 0.16 (0.00; 0.48) 0.10 (0; 0.30) 0.14 (0.00; 0.31) CUI- 0.80 (0.75; 0.84) 0.64 (0.59; 0.70) 0.56 (0.51; 0.61) 0.70 (0.59; 0.80) 0.70 (0.59; 0.80) 0.54 (0.43; 0.66) 0.85 (0.81; 0.89) 0.66 (0.61; 0.72) 0.61 (0.55; 0.66) PPV, % 80.95 (60.25; 92.26) 77.78 (54.49; 91.10) 88.57 (73.85; 95.51) 92.31 (62.81; 98.84) 85.71 (44.20; 97.85) 94.74 (71.87; 99.22) 62.50 (30.18; 86.54) 72.73 (46.41; 99.05) 81.25 (56.09; 93.63) NPV, % 82.27 (78.30; 85.65) 65.91 (63.28; 68.44) 57.71 (54.89; 60.49) 72.22 (62.05; 80.52) 72.22 (63.85; 79.29) 56.52 (48.79; 63.94) 87.70 (84.68; 90.20) 68.15 (60.87; 75.44) 62.21 (59.73; 64.92) Accuracy, % 82.10 (75.31; 87.67) 67.01 (59.91; 73.58) 62.29 (55.77; 68.49) 77.55 (63.38; 88.23) 74.42 (58.83; 86.48) 67.69 (54.95; 78.77) 86.15 (79.00; 91.58) 68.45 (60.85; 75.39) 63.83 (56.52; 70.70) Youden’s index 0.37 (0.17; 0.56) 0.16 (0.02; 0.29) 0.23 (0.11; 0.35) 0.51 (0.13; 0.76) 0.34 (-0.04; 0.64) 0.44 (0.12; 0.64) 0.22 (0.01; 0.49) 0.11 (-0.01; 0.23) 0.14 (0.01; 0.26) AUC 0.77 (0.68; 0.86)* 0.66 (0.58; 0.74)* 0.70 (0.64; 0.77)* 0.88 (0.77; 0.98)* 0.78 (0.63; 0.93)* 0.84 (0.74; 0.93)* 0.68 (0.53; 0.83)* 0.63 (0.54; 0.72)* 0.65 (0.56; 0.73)* MCC 0.49 0.26 0.33 0.57 0.44 0.47 0.33 0.21 0.25 > 10 cells/mm³ True Positive 14 6 20 9 2 11 5 4 9 Sensitivity, % 33.33 (19.57; 49.55) 8.11 (3.03; 16.82) 17.24 (10.86; 25.36) 40.91 (20.71; 63.65) 12.50 (1.55; 38.50) 28.95 (15.42; 45.90) 25.00 (8.66; 49.10) 6.90 (1.91; 16.73) 11.54 (5.41; 20.78) Specificity, % 99.17 (95.44; 99.98) 99.17 (95.44; 99.98) 99.17 (95.44; 99.98) 100.00 (87.23; 100.00) 100.00 (87.23; 100.00) 100.00 (87.23; 100.00) 98.92 (94.15; 99.97) 98.92 (94.15; 99.97) 98.92 (94.15; 99.97) LR (+) 40.00 (5.42; 295.01) 9.73 (1.19; 79.23) 20.69 (2.82; 151.68) - - - 23.25 (2.87; 188.35) 6.41 (0.73; 55.99) 10.73 (1.39; 82.86) LR (-) 0.67 (0.54; 0.83) 0.93 (0.86; 0.99) 0.83 (0.77; 0.91) 0.59 (0.42; 0.84) 0.88 (0.73; 1.05) 0.71 (0.58; 0.87) 0.76 (0.59; 0.98) 0.94 (0.87; 1.01) 0.89 (0.82; 0.97) DOR 59.50 (7.51; 471.59) 10.50 (1.24; 89.06) 24.79 (3.27; 188.07) 38.70 (2.09; 715.83) 9.48 (0.43; 210.99) 23.00 (1.29; 409.89) 30.67 (3.35; 281.05) 6.81 (0.74; 62.56) 12.00 (1.49; 96.97) CUI+ 0.31 (0.09; 0.53) 0.07 (0.00; 0.26) 0.16 (0.02; 0.31) 0.41 (0.13; 0.69) 0.13 (0.00; 0.52) 0.29 (0.06; 0.52) 0.21 (0.00; 0.54) 0.06 (0.00; 0.27) 0.12 (0.00; 0.31) CUI- 0.80 (0.76; 0.85) 0.63 (0.58; 0.68) 0.55 (0.50; 0.60) 0.68 (0.57; 0.78) 0.66 (0.55; 0.76) 0.50 (0.39; 0.61) 0.85 (0.81; 0.90) 0.62 (0.57; 0.68) 0.60 (0.54; 0.66) PPV, % 93.33 (65.50; 99.04) 85.71 (42.42; 97.99) 95.24 (73.18; 99.32) 100.00 100.00 100.00 83.33 (38.16; 97.59) 80.00 (31.42; 97.22) 45.61 (37.99; 53.39) NPV, % 80.95 (77.42; 84.04) 63.64 (62.01; 65.23) 55.35 (53.25; 57.43) 67.50 (59.46; 74.62) 65.85 (61.58; 69.89) 50.00 (44.94; 55.06) 85.98 (82.63; 88.77) 63.01 (61.29; 64.70) 90.00 (53.82; 98.58) Accuracy, % 82.10 (75.31; 87.67) 64.43 (57.26; 71.16) 58.90 (52.33; 65.24) 73.47 (58.92; 85.05) 67.44 (51.46; 80.92) 58.46 (45.56; 70.56) 85.84 (78.03; 91.88) 63.58 (55.36; 71.25) 57.14 (55.10; 59.16) Youden’s index 0.33 (0.15; 0.50) 0.08 (-0.80; 0.17) 0.16 (0.06; 0.25) 0.41 (0.08; 0.63) 0.13 (-0.11; 0.39) 0.29 (0.03; 0.46) 0.24 (0.03; 0.49) 0.05 (-0.04; 0.17) 0.10 (0.00; 0.21) AUC 0.77 (0.68; 0.86)* 0.66 (0.58; 0.74)* 0.70 (0.64; 0.77)* 0.88 (0.77; 0.98)* 0.78 (0.63; 0.93)* 0.84 (0.74; 0.93)* 0.68 (0.53; 0.83)* 0.63 (0.54; 0.72)* 0.65 (0.56; 0.73)* MCC 0.49 0.19 0.29 0.29 0.29 0.38 0.41 0.16 0.22 > 20 cells/mm³ True Positive 9 3 12 7 1 8 2 2 4 Sensitivity, % 21.43 (10.30; 36.81) 4.05 (0.84; 11.39) 10.34 (5.46; 17.37) 31.82 (13.86; 54.87) 6.25 (0.16; 30.23) 21.05 (9.55; 37.32) 10.00 (1.23; 31.70) 3.45 (0.42; 11.91) 5.13 (1.41; 12.61) Specificity, % 100.00 (96.97; 100.00) 100.00 (96.97; 100.00) 100.00 (96.97; 100.00) 100.0 (87.23; 100.0) 100.00 (87.23; 100.00) 100.00 (87.23; 100.00) 100.00 (96.11; 100.00) 100.00 (96.11; 100.00) 100.00 (96.11; 100.00) LR (+) - - - - - - - - - LR (-) 0.79 (0.67; 0.92) 0.96 (0.92; 1.01) 0.90 (0.84; 0.95) 0.68 (0.51; 0.91) 0.94 (0.83; 1.06) 0.79 (0.67; 0.93) 0.90 (0.78; 1.04) 0.97 (0.92; 1.01) 0.95 (0.90; 1.00) DOR 68.34 (3.88; 1204.79) 11.80 (0.60; 231.72) 28.83 (1.69; 492.85) 26.61 (1.42; 498.23) 5.32 (0.20; 138.74) 15.33 (0.84; 278.13) 25.27 (1.16; 548.25) 8.27 (0.39; 175.47) 11.30 (0.60; 213.15) CUI+ 0.21 (0.00; 0.45) 0.04 (0.00; 0.23) 0.10 (0.00; 0.25) 0.32 (0.02; 0.62) 0.06 (0.00; 0.47) 0.21 (0.00; 0.46) 0.11 (0.00; 0.49) 0.03 (0.00; 0.25) 0.05 (0.00; 0.24) CUI- 0.78 (0.74; 0.83) 0.63 (0.58; 0.68) 0.54 (0.49; 0.59) 0.64 (0.54; 0.75) 0.64 (0.54; 0.75) 0.47 (0.37; 0.58) 0.85 (0.81; 0.90) 0.62 (0.57; 0.68) 0.56 (0.50; 0.62) PPV, % 100.00 100.00 100.00 100.00 100.00 100.00 100.00 100.00 100.00 NPV, % 78.43 (75.64; 80.98) 62.83 (61.73; 63.91) 53.57 (52.03; 55.11) 64.29 (57.50; 70.54) 64.29 (61.33; 67.14) 47.37 (43.30; 51.47) 83.78 (81.70; 85.67) 62.42 (61.27; 63.55) 55.69 (54.41; 56.96) Accuracy, % 79.63 (72.60; 85.54) 63.40 (56.20; 70.19) 55.93 (49.35; 62.37) 69.39 (54.58; 81.75) 65.12 (49.07; 78.99) 53.85 (41.03; 66.30) 84.07 (76.00; 90.28) 62.91 (54.69; 70.63) 56.73 (48.94; 64.27) Youden’s index 0.21 (0.07; 0.37) 0.04 (-0.02; 0.11) 0.10 (0.02; 0.17) 0.32 (0.19; 0.55) 0.06 (-0.13; 0.30) 0.21 (-0.03; 0.37) 0.10 (-0.03; 0.32) 0.03 (-0.03; 0.12) 0.05 (-0.02; 0.13) AUC 0.77 (0.68; 0.86)* 0.66 (0.58; 0.74)* 0.70 (0.64; 0.77)* 0.88 (0.77; 0.98)* 0.78 (0.63; 0.93)* 0.84 (0.74; 0.93)* 0.68 (0.53; 0.83)* 0.63 (0.54; 0.72)* 0.65 (0.56; 0.73)* MCC 0.41 0.16 0.24 0.45 0.20 0.32 0.29 0.15 0.17 CUI values were classified as follows: excellent, ≥ 0.81; good, ≥ 0.64; fair, ≥ 0.49; poor, ≤ 0.49; and very poor, ≤ 0.36 [ 22 , 23 ]. An LR + value ≥ 10.0 indicates that a positive test almost confirmed the disease; a value of ∼6.0 indicates that the disease might be present; and a value of ∼1.0, indicating that the test was unable to determine the presence of the disease. An LR + value ≤ 0.1 indicates that the disease was practically absent [ 24 , 26 ]. Diagnostic odds ratio (DOR = LR+/LR-), the higher the DOR value the better the test [ 25 ]. The Matthews correlation coefficient (MCC) is a value between − 1 and + 1; a value of + 1 represents a perfect prediction, 0 indicates no better than random prediction, and − 1 indicates total disagreement between prediction and observation [ 27 ]. PWH, people with HIV; PWoH, people without HIV; G1, Confirmed NS; G2, Presumptive NS; G3, Systemic syphilis; G4, PWH without SS and/or NS; G5, Negative control. Positive and negative predictive values (PPV and NPV), positive and negative clinical utility index (CUI + and CUI−), positive and negative likelihood ratios (LR + and LR−), area under the ROC curve (AUC) (95% confidence interval), diagnostic odds ratio (DOR), Matthews correlation coefficient (MCC). (*) p 45 mg/dL or > 39 mg/dL, and combined CSF total protein > 45 mg/dL and/or CSF WBC > 5 cells/mm³, as adjunct biomarkers to diagnose confirmed and presumptive neurosyphilis in PWH and PWoH. Group Total PWH PWoH G1vs.G3 + 4 + 5 G2vs.G3 + 4 + 5 G1 + 2vs.G3 + 4 + 5 G1vs.G3 + 4 G2vs.G3 + 4 G1 + 2vs.G3 + 4 G1vs.G3 + 5 G2vs.G3 + 5 G1 + 2vs.G3 + 5 CSF total protein > 45 mg/dL True Positive 30 38 68 17 10 27 13 28 41 Sensitivity, % 71.43 (55.42; 84.28) 51.35 (39.44; 63.15) 58.62 (49.10; 67.69) 77.27 (54.63; 92.18) 62.50 (35.43; 84.80) 71.05 (54.10; 84.58) 65.00 (44.10; 85.90) 48.28 (35.42; 61.14) 52.56 (41.48; 63.65) Specificity, % 90.00 (83.18; 94.73) 90.00 (83.18; 94.73) 90.00 (83.18; 94.73) 70.37 (49.82; 86.25) 70.37 (49.82; 86.25) 70.37 (49.82; 86.25) 95.70 (91.58; 99.82) 95.70 (91.58; 99.82) 95.70 (91.58; 99.82) LR (+) 7.14 (4.04; 12.63) 5.14 (2.87; 9.18) 5.86 (3.35; 10.24) 2.61 (1.40; 4.87) 2.11 (1.05; 4.22) 2.40 (1.30; 4.44) 15.11 (5.50; 41.54) 11.22 (4.15; 30.36) 12.22 (4.58; 32.61) LR (-) 0.32 (0.20; 0.51) 0.54 (0.42; 0.69) 0.46 (0.37; 0.58) 0.32 (0.14; 0.72) 0.53 (0.27; 1.05) 0.41 (0.24; 0.72) 0.37 (0.20; 0.67) 0.54 (0.42; 0.70) 0.50 (0.39; 0.63) DOR 22.50 (9.18; 55.15) 9.50 (4.48; 20.12) 12.75 (6.32; 25.72) 8.08 (2.21; 29.48) 3.96 (1.07; 14.62) 5.83 (1.97; 17.23) 41.32 (10.61; 160.89) 20.77 (6.73; 64.06) 24.66 (8.24; 73.77) CUI+ 0.51 (0.34; 0.68) 0.39 (0.24; 0.54) 0.50 (0.39; 0.61) 0.53 (0.31; 0.75) 0.35 (0.06; 0.63) 0.55 (0.37; 0.72) 0.50 (0.24; 0.75) 0.42 (0.26; 0.59) 0.48 (0.34; 0.62) CUI- 0.81 (0.76; 0.86) 0.68 (0.62; 0.73) 0.62 (0.57; 0.68) 0.56 (0.41; 0.71) 0.54 (0.39; 0.68) 0.45 (0.30; 0.59) 0.89 (0.85; 0.93) 0.72 (0.66; 0.77) 0.68 (0.62; 0.73) PPV, % 71.43 (58.58; 81.55) 76.00 (63.92; 84.99) 85.00 (76.43; 90.83) 68.00 (53.24; 79.86) 55.56 (38.44; 71.45) 77.14 (64.58; 86.20) 76.47 (56.31; 96.63) 87.50 (76.04; 98.96) 91.11 (82.80; 99.43) NPV, % 90.00 (78.76; 90.27) 75.00 (70.20; 79.25) 69.23 (64.25; 73.80) 79.17 (62.87; 89.51) 76.00 (61.64; 86.19) 63.33 (49.79; 75.06) 92.71 (87.51; 97.91) 74.79 (66.99; 82.59) 70.63 (62.68; 78.59) Accuracy, % 85.19 (78.76; 90.27) 75.26 (68.57; 81.16) 74.58 (68.52; 80.00) 73.47 (58.92; 85.05) 67.44 (51.46; 80.92) 70.77 (58.17; 81.40) 90.27 (83.25; 95.04) 48.28 (34.95; 61.78) 76.02 (68.91; 82.21) Youden’s index 0.61 (0.39; 0.79) 0.41 (0.23; 0.58) 0.49 (0.32; 0.62) 0.48 (0.04; 0.78) 0.33 (-0.15; 0.71) 0.41 (0.04; 0.71) 0.60 (-0.64; -0.14) 0.44 (0.27; -0.39) 0.48 (0.33; 0.63) AUC 0.89 (0.83; 0.95)* 0.82 (0.76; 0.88)* 0.84 (0.79; 0.89)* 0.79 (0.67; 0.92)* 0.72 (0.57; 0.88)* 0.76 (0.64; 0.88)* 0.91 (0.83; 0.98)* 0.86 (0.76; 0.89)* 0.85 (0.79; 0.90)* MCC 0.61 0.46 0.51 0.49 0.32 0.41 0.62 0.52 0.55 CSF total protein > 39 mg/dL True Positive 34 44 78 17 12 29 17 32 49 Sensitivity, % 80.95 (65.88; 91.40) 59.46 (47.41; 770.73) 67.24 (57.91; 75.67) 77.27 (54.63; 92.18) 75.00 (47.62; 92.73) 76.32 (59.76; 88.56) 85.00 (62.11; 96.79) 55.17 (41.54; 68.26) 62.82 (51.13; 73.50) Specificity, % 80.83 (72.64; 87.44) 80.83 (72.64; 87.44) 80.83 (72.64; 87.44) 66.67 (46.04; 83.48) 66.67 (46.04; 83.48) 66.67 (46.04; 83.48) 84.95 (76.03; 91.52) 84.95 (76.03; 91.52) 84.95 (76.03; 91.52) LR (+) 4.22 (2.84; 6.27) 3.10 (2.05; 4.69) 3.51 (2.38; 5.18) 2.32 (1.30; 4.14) 2.25 (1.23; 4.12) 2.29 (1.31; 4.02) 5.65 (3.37; 9.47) 3.67 (2.15; 6.26) 4.17 (2.50; 6.96) LR (-) 0.24 (0.13; 0.44) 0.50 (0.38; 0.67) 0.41 (0.31; 0.53) 0.34 (0.15; 0.77) 0.38 (0.15; 0.91) 0.36 (0.19; 0.67) 0.18 (0.06; 0.50) 0.53 (0.39; 0.71) 0.44 (0.32; 0.59) DOR 17.92 (7.33; 43.84) 6.19 (3.23; 11.84) 8.66 (4.76; 15.73) 6.80 (1.89; 24.42) 6.00 (1.50; 23.99) 6.44 (2.16; 19.27) 31.98 (8.27; 123.67) 6.94 (3.22; 14.98) 9.53 (4.59; 19.80) CUI+ 0.48 (0.33; 0.64) 0.39 (0.25; 0.53) 0.52 (0.42; 0.62) 0.51 (0.28; 0.73) 0.43 (0.16; 0.69) 0.58 (0.42; 0.75) 0.47 (0.25; 0.68) 0.38 (0.22; 0.55) 0.49 (0.36; 0.62) CUI- 0.75 (0.69; 0.80) 0.62 (0.56; 0.68) 0.58 (0.52; 0.64) 0.52 (0.37; 0.68) 0.55 (0.39; 0.70) 0.44 (0.29; 0.60) 0.82 (0.77; 0.87) 0.64 (0.57; 0.71) 0.62 (0.55; 0.69) PPV, % 59.65 (49.88; 68.71) 65.67 (55.87; 74.30) 77.23 (69.69; 83.34) 65.38 (51.41; 77.13) 57.14 (42.16; 70.92) 76.32 (64.75; 84.97) 54.84 (42.01; 67.06) 59.57 (57.23; 79.61) 77.78 (67.71; 85.38) NPV, % 92.38 (86.60; 95.79) 76.38 (70.77; 81.20) 71.85 (65.98; 77.07) 78.26 (61.43; 89.05) 81.82 (64.90; 91.63) 66.67 (51.58; 78.97) 96.34 (90.24; 98.68) 75.24 (69.28; 80.37) 73.15 (66.85; 78.63) Accuracy, % 80.86 (73.95; 86.61) 72.68 (65.84; 78.82) 74.15 (68.07; 79.61) 71.43 (56.74; 83.42) 69.77 (53.87; 82.82) 72.31 (59.81; 82.69) 84.96 (77.01; 90.99) 73.51 (65.72; 80.35) 74.85 (67.66; 81.16) Youden’s index 0.61 (0.39; 0.79) 0.41 (0.23; 0.58 0.49 (0.32; 0.62) 0.48 (0.04; 0.78) 0.33 (-0.15; 0.71) 0.41 (0.04; 0.71) 0.61 (0.36; 0.86) 0.44 (0.27; 0.61) 0.48 (0.33; 0.63) AUC 0.89 (0.83; 0.95)* 0.82 (0.76; 0.88)* 0.84 (0.79; 0.89)* 0.79 (0.67; 0.92)* 0.72 (0.57; 0.88)* 0.76 (0.64; 0.88)* 0.91 (0.83; 0.98)* 0.86 (0.76; 0.89)* 0.85 (0.79; 0.90)* MCC 0.57 0.41 0.49 0.44 0.40 0.43 0.60 0.42 0.49 CSF total protein > 45 mg/dL and/or WBC > 5 cells/mm³ True Positive 31 41 72 18 11 29 13 30 43 Sensitivity, % 73.81 (60.51; 87.11) 55.41 (44.08; 66.73) 62.07 (53.24; 70.90) 81.82 (59.72; 94.81) 68.75 (41.34; 88.98) 76.32 (59.76; 88.56) 65 (40.78; 84.61) 51.72 (38.22; 65.05) 55.13 (43.44; 66.41) Specificity, % 87.50 (81.58; 93.42) 87.50 (81.58; 93.42) 87.50 (81.58; 93.42) 70.37 (49.82; 86.25) 70.37 (49.82; 86.25) 70.37 (49.82; 86.25) 92.47 (85.10; 96.92) 92.47 (85.10; 96.92) 92.47 (85.10; 96.92) LR (+) 5.91 (3.56; 9.80) 4.43 (2.65; 7.42) 4.97 (3.03; 8.14) 2.76 (1.49; 5.10) 2.32 (1.19; 4.53) 2.58 (1.40; 4.73) 8.64 (3.95; 18.87) 6.87 (3.23; 14.61) 7.32 (3.49; 15.35) LR (-) 0.30 (0.18; 0.50) 0.51 (0.39; 0.66) 0.43 (0.34; 0.55) 0.26 (0.10; 0.65) 0.44 (0.21; 0.96) 0.34 (0.18; 0.63) 0.38 (0.21; 0.69) 0.52 (0.40; 0.69) 0.49 (0.38; 0.62) DOR 19.78 (8.22; 47.33) 8.70 (4.28; 17.67) 11.46 (5.93; 22.12) 4.50 (0.87; 23.35) 2.75 (0.51; 14.86) 7.65 (2.51; 23.32) 22.82 (6.88; 75.68) 13.16 (5.21; 33.25) 15.09 (6.20; 36.77) CUI+ 0.50 (0.33; 0.66) 0.41 (0.26; 0.55) 0.51 (0.41; 0.62) 0.57 (0.36; 0.78) 0.40 (0.12; 0.68) 0.60 (0.43; 0.76) 0.42 (0.17; 0.68) 0.42 (0.26; 0.58) 0.17 (0.00; 0.38) CUI- 0.79 (0.74; 0.84) 0.67 (0.61; 0.72) 0.62 (0.56; 0.68) 0.58 (0.44; 0.73) 0.56 (0.41; 0.71) 0.48 (0.33; 0.63) 0.86 (0.81; 0.90) 0.70 (0.64; 0.757) 0.59 (0.51; 0.67) PPV, % 67.39 (53.84; 80.94) 73.21 (61.62; 84.81) 82.76 (74.82; 90.70) 69.23 (54.91; 80.61) 57.89 (41.33; 72.85) 78.38 (66.38; 86.94) 65.00 (45.94; 80.23) 81.08 (66.84; 90.11) 86.00 (74.56; 92.79) NPV, % 90.52 (85.19; 95.85) 76.09 (68.97; 83.20) 70.47 (63.14; 77.79) 82.61 (65.44; 92.26) 79.17 (63.83; 89.11) 67.86 (53.15; 79.71) 92.47 (87.08; 95.72) 75.44 (70.05; 80.14) 71.07 (65.62; 75.98) Accuracy, % 83.95 (77.37; 89.24) 75.26 (68.57; 81.16) 75.00 (68.97; 80.39) 75.51 (61.13; 86.66) 69.77 (53.87; 82.82) 73.85 (61.46; 83.97) 87.61 (80.09; 93.06) 76.82 (69.27; 83.29) 75.44 (68.28; 81.69) Youden’s index 0.61 (0.42; 0.81) 0.43 (0.26; 0.60) 0.50 (0.41; 0.64) 0.52 (0.10) 0.39 (-0.09; 0.75) 0.47 (0.10; 0.75) 0.57 (0.26; 0.82) 0.44 (0.23; 0.62) 0.48 (0.29; 0.63) AUC 0.81 (0.72; 0.89)* 0.71 (0.64; 0.79)* 0.75 (0.68; 0.81)* 0.86 (0.76; 0.97)* 0.76 (0.60; 0.91)* 0.82 (0.73; 0.91)* 0.67 (0.52; 0.83)* 0.60 (0.48; 0.72) 0.62 (0.50; 0.73) MCC 0.57 0.46 0.51 0.52 0.38 0.47 0.58 0.50 0.52 CUI values were classified as follows: excellent, ≥ 0.81; good, ≥ 0.64; fair, ≥ 0.49; poor, ≤ 0.49; and very poor, ≤ 0.36 [ 22 , 23 ]. An LR + value ≥ 10.0 indicates that a positive test almost confirmed the disease; a value of ∼6.0 indicates that the disease might be present; and a value of ∼1.0, indicating that the test was unable to determine the presence of the disease. An LR + value ≤ 0.1 indicates that the disease was practically absent [ 24 , 26 ]. Diagnostic odds ratio (DOR = LR+/LR-), the higher the DOR value the better the test [ 25 ]. The Matthews correlation coefficient (MCC) is a value between − 1 and + 1; a value of + 1 represents a perfect prediction, 0 indicates no better than random prediction, and − 1 indicates total disagreement between prediction and observation [ 27 ]. PWH, people with HIV; PWoH, people without HIV; G1, Confirmed NS; G2, Presumptive NS; G3, Systemic syphilis; G4, PWH without SS and/or NS; G5, Negative control. Positive and negative predictive values (PPV and NPV), positive and negative clinical utility index (CUI + and CUI−), positive and negative likelihood ratios (LR + and LR−), area under the ROC curve (AUC) (95% confidence interval), diagnostic odds ratio (DOR), Matthews correlation coefficient (MCC). (*) p < 0.05, p value indicated the difference between the AUC of the ROC curve and the baseline (random line). Overall, the DCPC of CSF TP, as a single test, was higher in PWoH than in PWH, despite the cutoff point applied. AUC and MCC were higher in PWoH than in PWH (Fig. 3 and Table 4 ). The best cutoff point calculated for CSF TP was > 39 mg/dL; for CSF TP, this cutoff sensitivity and NPV were higher than the cutoff point of > 45 mg/dL, but with lower specificity in all groups analyzed. LR + and LR- were higher with a cutoff point of 45 mg/dL, indicating that the chance of a positive test confirming the disease was more significant with this cutoff (Table 4 ). The post-test diagnostic probability for a positive and negative test of CSF TP or CSF WBC single tests to diagnose confirmed NS in PWH and/or PWoH is shown in Figs. 4 and Supplementary Fig. 1. The DCPC of the association of CSF TP (> 45 mg/dL) and/or WBC count (> 5 cells/mm³) as adjunct biomarkers to diagnose confirmed or presumptive NS in PWH or PWoH is shown in Table 4 and Fig. 3 . 3.4 CSF Lactate Among PWH and PWoH, CSF LA levels were within the reference ranges and comparable between the NS and SS groups (Table 1 ). For PWH the AUC of CSF LA (mmol/L) to diagnose confirmed and presumptive NS (G1 and G2) was 0.69 (0.53, 0.85; p = 0.025), whereas that for PWoH was 0.54 (0.45, 0.64; p = 0.387). Overall, the participants the AUC was 0.58 (0.49, 0.66; p = 0.069). 4. DISCUSSION In contrast to most published studies that analyzed these groups together [Dumaresq et al. 2013; Ghanem et al. 2008; Lee et al. 2015; Dunaway et al. 2020; Cai et al. 2017; He et al. 2021; Li et al. 2019; Lin et al. 2014; Pastuszczak et al. 2013], we analyzed CSF biomarkers in symptomatic confirmed and presumptive NS separately. Analysis of the DCPC of these CSF biomarkers in presumptive NS is particularly important, as CSF nontreponemal antibody assays are negative [Wharton et al. 1990]. In our study, elevation of CSF WBC and TP was more frequent in PWH than in PWoH. In PWH among confirmed than in presumptive NS. In confirmed NS, CSF WBC > 5 cells/mm 3 and CSF protein > 45 mg/dL was observed in 30% and 74%, respectively, whereas in presumptive NS, CSF WBC > 5 cells/mm 3 and CSF protein > 45 mg/dL was observed in 28% and 91%, respectively; both were significantly different [Jiang et al. 2018]. In PWH, symptomatic NS patients showed more CSF abnormalities on the initial LP than asymptomatic patients; CSF WBC > 10 cells/ mm 3 was observed in 70% of symptomatic NS and 46% of the asymptomatic NS. CSF protein > 50 mg/dL was present in 61% of symptomatic NS, and 58% of the asymptomatic [Ghanem et al. 2008]. In PWH with early syphilis, CSF WBC > 20 cells/mm 3 was observed in 37% [Dumaresq et al. 2013]. PWH with ocular syphilis CSF WBC > 5 cells/mm 3 was observed in 37.50%, and CSF TP > 40 mg/dL in 56% [Lee et al. 2015]. Between PWH and PWoH with confirmed and presumptive NS altogether, including 44% with symptomatic NS, CSF WBC > 20 cells/mm 3 was observed in 63% and CSF TP > 50 mg/dL in 61% [Dunaway et al. 2020]. However, among asymptomatic NS in PWoH, CSF WBC > 5 cells/mm 3 was observed in 83%, CSF WBC > 20 cells/mm 3 in 5%, CSF protein > 45 mg/dL was observed in 20% [Cai et al. 2017]. A previous study reported PWoH CSF WBC > 5 cells/ mm 3 in ~ 81% of symptomatic and asymptomatic NS [ 38 , 40 ]. Increased CSF TP > 45 or 50 mg/dL was observed in 68–78% of symptomatic NS, but less frequently in asymptomatic NS, between 29–51% [He et al. 2021; Li et al. 2019]. In PWoH with symptomatic NS and psychiatric manifestations, CSF WBC > 10 cells/ mm 3 was observed in 54%, CSF TP > 50 mg/dL in 60%, and both CSF TP > 50 mg/dL and CSF WBC > 10 cells/mm 3 in 44% [Lin et al. 2014]. In PWoH with secondary and early latent syphilis and a serum VDRL ≥ 1:32, symptomatic and asymptomatic NS, CSF WBC > 5 cells/mm 3 was observed in 42%, CSF WBC > 10 cells/mm 3 in 30%, and CSF WBC > 20 cells/ mm 3 in 18%. CSF TP > 45 mg/dL in 39%, CSF TP > 45 mg/dL, and CSF WBC > 5 cells/mm 3 in 30% [Pastuszczak et al. 2013]. The prevalence of abnormal CSF protein concentrations varies depending on the clinical form of neurosyphilis [Simon 1985]. In this study for the DCPC of CSF TP with cutoff > 45 mg/dL, the sensitivity is low for diagnosis of confirmed NS in PWoH, meaning a positive test does not often occur in those with the condition, and the specificity is high, meaning a negative test often occurs in those without confirmed NS. The PPV of the test is low, false positives are common in those who screen positive, possibly limiting confirmation. The NPV of the test is high, indicating that false negatives are uncommon in those who screen negative. The clinical utility of the test is very poor for confirmation but excellent for screening. The value of the CSF TP > 45 mg/dL single test for both screening and confirmation is good, but depends on prevalence. However, in PWH, the value of the CSF TP with a cutoff > 45 mg/dL for both screening and confirmation, NS is fair and subject to prevalence. Concerning the diagnosis of presumptive NS in PWoH, the DCPC of CSF TP > 45 mg/dL were lower than that for the diagnosis of confirmed NS. The sensitivity of the test was very low, but its specificity was high. The PPV and NPV of the test are modest, meaning that false positives or negatives are common. The clinical utility of the test is very poor for confirmation but good for screening. The value of CSF TP > 45 mg/dL for both screening and confirmation is fair and subject to prevalence. However, in PWH, the sensitivity of CSF TP > 45 mg/dL is very low, indicating that a positive test rarely occurs in those with presumptive NS. The specificity of the test is low, meaning that a negative test result does not often occur in those without the condition. The PPV and NPV of the test is very low, the value of CSF TP > 45 mg/dL to diagnose presumptive NS in PWH for both screening and case finding is poor. In our study, in PWoH, the DCPC of CSF WBC to diagnose confirmed NS, with a cutoff CSF WBC > 20 cells/mm 3 , has extremely low sensitivity and very high specificity. The PPV of the test is almost perfect, meaning that false positives are rare in those who screen positive, suggesting a potentially useful confirmatory test. The NPV of the test is modest, meaning that occasional false negatives occur among those who screen negative. The clinical utility of the test is very poor for case finding, but good for screening. However, in the PWH group, the DCPC of CSF WBC with a cutoff > 5 cells/mm 3 , the sensitivity of the test is very low and the specificity is high for diagnosing confirmed NS. The PPV of the test is modest, meaning that false positives are a little more common in those who screen positive. The NPV of the test is low, indicating that false negatives are common in those who screen negative, possibly limiting screening applications. The clinical utility of the test is very poor for confirmation, and fair for screening. The value of this single test for both screening and confirmation is fair and subject to prevalence. However, in the PWH group for CSF WBC with a cutoff > 10 or 20 cells/mm 3 , the specificity of the test is very high, meaning a negative test often occurs in those without the condition, which is in accordance with a previous report [Marra et al. 1996; Marra 2007]. The PPV of the test is almost perfect, meaning that false positives are rare in those who screen positive, offering a candidate confirmatory test. The value of CSF WBC > 10 or 20 cells/mm 3 was considered moderate for screening. In the PWH for WBC count, with the cutoffs > 10 or > 20 cells/mm 3 , the PPV is almost perfect for the diagnosis of presumptive NS, meaning false positives are very rare in those who screen positive, suggesting a candidate confirmatory test. These cutoff values are moderate for screening. However, in the PWoH group, WBC count for the diagnosis of presumptive NS showed the worst DCPC. The best characteristic for CSF WBC count > 20 cells/mm 3 was the specificity of the test, which was very high. The PPV of the test was almost perfect, suggesting that it represents a potentially useful confirmatory test. The clinical utility of the screening test was fair. CSF pleocytosis in syphilis is lymphocyte predominant. Polymorphonuclear lymphocytes may predominate, particularly in cases of acute syphilitic meningitis [Ghanem 2010]. A cutoff of ≥ 5 cells/mL has been the standard; this has less specificity among PWH owing to nonspecific abnormalities associated with the HIV infection itself [Marra et al. 1996; Spudich et al. 2005]. Our findings support previous studies on PWH-confirmed and presumptive NS. Because HIV can cause mild mononuclear CSF pleocytosis, 15.6% of CSF samples from PWH had > 10 cells/mm 3 with progressive decline in CSF WBC count with advancing stages of AIDS [Marshall et al. 1988]. Limited data suggest a cutoff of 10 cells/mL for PWH when the peripheral blood CD4 T cell concentration is low or patients are on antiretrovirals, because these lower the risk of HIV-related pleocytosis [Ghanem et al. 2008], and 20 cells/mL for those not on antiretroviral therapy may improve the specificity for diagnosing neurosyphilis [Marra et al. 2007]. In this study the combination of CSF TP > 45 mg/dL and/or WBC > 5.0 cells/mm 3 , in PWoH for the diagnosis of confirmed NS, the value for both screening and confirmation is good, but depends on the prevalence. This combination was excellent for screening. However, in PWoH for diagnosis of presumptive NS, this combination is suitable for screening, and its best feature is its specificity. In PWH, the same combination for the diagnosis of confirmed or presumptive had low sensitivity. The PPV and NPV of the combination were both low, possibly limiting confirmation and screening applications. The clinical utility of the test for confirmation and screening are very poor and is therefore not recommended for either application. Most studies investigating the DCPC of CSF TP and WBC were performed in PWoH, with few in PWH. Furthermore, few have previously investigated DCPC separately on confirmed and presumptive NS. A study in PWoH, analyzing separately confirmed and presumptive NS, as in our study, the sensitivity and specificity of CSF WBC > 10 cells/mm³ were 65.38% and 75.26% for diagnosing confirmed NS and 64.71% and 76.81% for presumptive NS, respectively. For CSF TP > 50 mg/dL, the sensitivity was 53.85% and 55.56% for confirmed and presumptive NS, respectively, and specificity was 86.05% and 68.12%, respectively [Lin et al. 2016]. In other studies, in PWoH, to diagnose confirmed and presumptive NS together, sensitivities and specificities for CSF WBC > 3 cells/mm³ were 48.00% and 82.00%, respectively; for CSF TP > 49.7 mg/dL, they were 54.00% and 85.71%, respectively; for the association of CSF TP > 49.7 mg/dL, CSF WBC > 3 cells/mm³, and neurological symptoms were 92.50% and 33.30%, respectively [Tong et al. 2013]. The sensitivity and specificity of CSF WBC > 10 cells/mm³ to diagnose confirmed NS and presumptive NS together were 59.50% and 92.50%, respectively [Liu et al. 2013]. A lower cutoff point for PWH CSF TP, such as 39 mg/dL, proved advantageous, especially for increasing diagnostic sensitivity. These findings reinforce previous guidelines, which recommended CSF TP cutoff point > 40 mg/dL [Workowski and Bolan 2015; Klein et al. 2020]. CSF LA do not add to the diagnose of NS, however among PWH and PWoH, CSF LA is suitable for discriminating between other causes of chronic meningitis with an increase in CSF LA, such as tuberculous meningitis or Cryptococcus sp [de Almeida et al. 2022]. The results of this study were limited mainly by its retrospective nature; some analyses were limited by the small sample sizes. CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, which were better in the former. HIV co-infection greatly affects the DCPC of these biomarkers for the diagnosis of NS. The development of novel NS diagnostics is of paramount importance, particularly in settings where non-treponemal tests are negative with high clinical suspicion [Boog et al. 2021; Marks et al. 2018; Ramachandran and Wilson 2020]. Declarations Ethical Approval This study was conducted in accordance with the principles of the Declaration of Helsinki. The protocols were approved by the Institutional Review Board of the Hospital de Clínicas, Universidade Federal do Paraná (Curitiba, Paraná, Brazil). Written informed consent was waived by the local IRB. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Competing Interests Statement The authors have no competing interests to declare regarding the publication of this article. Availability of data and materials Prof. Sergio Monteiro de Almeida, declare that he has full access to all of the data. Anonymized data from the current study will be made available at the request of qualified investigators if approved by our Research Ethics Board. Author Contribution S.M.A. participated in the conception and design of the work, revised the manuscript critically for important intellectual content; S.M.A. and J.T.N. participated in the acquisition, analysis, and interpretation of data; prepared all figures and tables; A.M.R, A.C.M., and D.Z.G participated in the data acquisition; F.G. participated in the design of the work; data analysis and revised it critically. All authors approved the version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. References Guarner J, Jost H, Pillay A, Sun Y, Cox D, Notenboom R, Workowski K (2015) Evaluation of Treponemal Serum Tests Performed on Cerebrospinal Fluid for Diagnosis of Neurosyphilis. Am J Clin Pathol 143(4):479–484. https://doi.org/10.1309/AJCPWSL3G8RXMCQR Yu J, Shi JC, Wan H, Li J, Shao Y, Ye J, Dai L, Wang X, Liu A (2021) Clinical characteristics, diagnosis, and predictors of neurosyphilis patients with human immunodeficiency virus co-infection: A retrospective study at infectious diseases hospitals in two cities of China. Medicine 100(42):e27430. https://doi.org/10.1097/MD.0000000000027430 Dumaresq J, Langevin S, Gagnon S, Serhir B, Deligne B, Tremblay C, Tsang RSW, Fortin C, Coutlee F, Roger M (2013) Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis. J Clin Microbiol 51(12):4060. https://doi.org/10.1128/JCM.01989-13 Salamano R, Ballesté R, Perna A, Rodriguez N, Lombardo D, García N, López P, Cappuccio P (2016) Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV + patients with syphilis. Arq Neuropsiquiatr 74(2):128–132. https://doi.org/10.1590/0004-282X20160016 Feraru ER, Aronow HA, Lipton RB (1990) Neurosyphilis in AIDS patients: initial CSF VDRL may be negative. Neurology 40(3 Pt 1):541–543. https://doi.org/10.1212/WNL.40.3_PART_1.541 Brasil, Ministério da Saúde (2018) Protocolo Clínico e Diretrizes Terapêuticas para Manejo da Infecção pelo HIV em Adultos / Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis. Available from: http://www.aids.gov.br/assistencia/manualdst/item12.html Brasil, Ministério da Saúde (2011) Fluxograma Laboratorial da Sífilis e a utilização de testes rápidos para triagem da sífilis em situações especiais e apresenta outras recomendações. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/gm/2011/prt3242_30_12_2011.html Brasil, Ministério da Saúde (2022) Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infecções sexualmente transmissíveis (IST). Secretária Vigilância em Saúde. Available from: http://bvsms.saude.gov.br/bvs/publicacoes/protocolo_clinico_atecao_integral_ist.pdf Wharton M, Chorba TL, Vogt RL, Morse DL, Buehler JW (1990) Case definitions for public health surveillance. MMWR Recomm Rep 39(RR–13):1–43 PMID: 2122225 French P, Gomberg M, Janier M, Schmidt BL, van Voorst Vader PC, Young H (2009) IUSTI: 2008 European Guidelines on the Management of Syphilis. Int J STD AIDS 20(5):300–309. https://doi.org/10.1258/IJSA.2008.008510 Workowski KA, Bolan GA (2015) Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report. Recommendations and Reports, 64(RR-03), 1. https://doi.org/10.1097/00019048-200206000-00012 Izzat NN, Bartruff JK, Glicksman JM, Holder WR, Knox JM (1971) Validity of the VDRL test on cerebrospinal fluid contaminated by blood. Br J Vener Dis 47(3):162. https://doi.org/10.1136/STI.47.3.162 Rotta O (2005) Serological diagnosis of syphilis * Diagnóstico sorológico da sífilis *. An Bras Dermatol 80(3):299–302 Marra CM (2015) Neurosyphilis. In CONTINUUM Lifelong Learning in Neurology (Vol. 21, Issue 6). https://doi.org/10.1212/CON.0000000000000250 Zhu L, Gu X, Peng RR, Wang C, Gao Z, Zhou P, Gao Y, Shi M, Guan Z, Señac AC (2014) Comparison of the cerebrospinal fluid (CSF) toluidine red unheated serum test and the CSF rapid plasma reagin test with the CSF Venereal Disease Research Laboratory test for diagnosis of neurosyphilis among HIV-negative syphilis patients in China. J Clin Microbiol 52(3):736–740. https://doi.org/10.1128/JCM.02522-13/SUPPL_FILE/ZJM999093171SO1.PDF Boog GHP, Lopes JVZ, Mahler JV, Solti M, Kawahara LT, Teng AK, Munhoz JVT, Levin AS (2021) Diagnostic tools for neurosyphilis: a systematic review. BMC Infect Dis 21(1):1–12. https://doi.org/10.1186/S12879-021-06264-8/FIGURES/4 Gonzalez H, Koralnik IJ, Marra CM (2019) Neurosyphilis Seminars in Neurology 39(04):448–455. https://doi.org/10.1055/S-0039-1688942 Ropper AH (2019) Neurosyphilis. Https://Doi.Org/10.1056/NEJMra1906228 , 381(14), 1358–1363. https://doi.org/10.1056/NEJMRA1906228 Larsen SA, Steiner BM, Rudolph AH (1995) Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 8(1):1. https://doi.org/10.1128/CMR.8.1.1 de Almeida SM, Barros N, Fernandes Dos Santos A, Custodio G, Petterle RR, Nogueira K, Nogueira MB (2020) Clinical performance of amperometry compared with enzymatic ultra violet method for lactate quantification in cerebrospinal fluid. Diagnosis (Berlin Germany) 8(4):510–514. https://doi.org/10.1515/DX-2020-0065 Deisenhammer F, Bartos A, Egg R, Gilhus NE, Giovannoni G, Rauer S, Sellebjerg F (2006) Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol 13(9):913–922. https://doi.org/10.1111/J.1468-1331.2006.01493.X Mitchell AJ (2008) The clinical significance of subjective memory complaints in the diagnosis of mild cognitive impairment and dementia: a meta-analysis. Int J Geriatr Psychiatry 23(11):1191–1202. https://doi.org/10.1002/GPS.2053 Mitchell AJ (2011) Sensitivity × PPV is a recognized test called the clinical utility index (CUI+). Eur J Epidemiol 2011 26(3):251–252. https://doi.org/10.1007/S10654-011-9561-X Akobeng AK (2007a) Understanding diagnostic tests 2: likelihood ratios, pre- and post-test probabilities and their use in clinical practice. Acta Paediatrica (Oslo, Norway: 1992), 96(4), 487–491. https://doi.org/10.1111/J.1651-2227.2006.00179.X Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PMM (2003) The diagnostic odds ratio: A single indicator of test performance. J Clin Epidemiol 56(11):1129–1135. https://doi.org/10.1016/S0895-4356(03)00177-X McGee S (2002) Simplifying Likelihood Ratios. J Gen Intern Med 17(8):647. https://doi.org/10.1046/J.1525-1497.2002.10750.X Matthews BW (1975) Comparison of the predicted and observed secondary structure of T4 phage lysozyme. Biochim Biophys Acta 405(2):442–451. https://doi.org/10.1016/0005-2795(75)90109-9 Sackett DL, Haynes RB (2002) Evidence base of clinical diagnosis: The architecture of diagnostic research. BMJ: Br Med J 324(7336):539. https://doi.org/10.1136/BMJ.324.7336.539 TJ F (1975) Letter: Nomogram for Bayes theorem. N Engl J Med 293(5):257–257. https://doi.org/10.1056/NEJM197507312930513 Akobeng AK (2007b) Understanding diagnostic tests 3: Receiver operating characteristic curves. Acta Paediatrica (Oslo, Norway: 1992), 96(5), 644–647. https://doi.org/10.1111/J.1651-2227.2006.00178.X de Almeida SM, Bhatt A, Riggs PK, Durelle J, Lazzaretto D, Marquie-Beck J, McCutchan A, Letendre S, Ellis R (2010) Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis. J Neurovirol 16(1):6. https://doi.org/10.3109/13550280903514776 Fan L, Yu A, Zhang D, Wang Z, Ma P (2021) Consequences of HIV/Syphilis Co-Infection on HIV Viral Load and Immune Response to Antiretroviral Therapy. Infect Drug Resist 14:2851. https://doi.org/10.2147/IDR.S320648 Palacios R, Jiménez-Oñate F, Aguilar M, Galindo MJ, Rivas P, Ocampo A, Berenguer J, Arranz JA, Ríos MJ, Knobel H, Moreno F, Ena J, Santos J (2007) Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes (1999), 44(3), 356–359. https://doi.org/10.1097/QAI.0B013E31802EA4C6 Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA, London AIDS (2008) England), 22(10), 1145. https://doi.org/10.1097/QAD.0B013E32830184DF Lee SY, Cheng V, Rodger D, Rao N (2015) Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection. J Ophthalmic Inflamm Infect 5(1). https://doi.org/10.1186/S12348-015-0056-X Dunaway SB, Maxwell CL, Tantalo LC, Sahi SK, Marra CM (2020) Neurosyphilis Treatment Outcomes After Intravenous Penicillin G Versus Intramuscular Procaine Penicillin Plus Oral Probenecid. 71(2):267. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America https://doi.org/10.1093/CID/CIZ795 Cai SN, Long J, Chen C, Wan G, Lun WH (2017) Incidence of asymptomatic neurosyphilis in serofast Chinese syphilis patients. Sci Rep 7(1). https://doi.org/10.1038/S41598-017-15641-W He C, Kong Q, Shang X, Duan Y, Cui Y, Wang J, Ci C, Sang H (2021) Clinical, laboratory and brain Magnetic Resonance Imaging (MRI) characteristics of asymptomatic and symptomatic HIV-negative neurosyphilis patients. J Infect Chemotherapy: Official J Japan Soc Chemother 27(11):1596–1601. https://doi.org/10.1016/J.JIAC.2021.07.004 Li W, Jiang M, Xu D, Kou C, Zhang L, Gao J, Qin K, Wu W, Zhang X (2019) Clinical and Laboratory Characteristics of Symptomatic and Asymptomatic Neurosyphilis in HIV-Negative Patients: A Retrospective Study of 264 Cases. BioMed Research International, 2019. https://doi.org/10.1155/2019/2426313 Lin LR, Zhang HL, Huang SJ, Zeng YL, Xi Y, Guo XJ, Liu GL, Tong ML, Zheng WH, Liu LL, Yang TC (2014) Psychiatric manifestations as primary symptom of neurosyphilis among HIV-negative patients. J Neuropsychiatry Clin Neurosci 26(3):233–240. https://doi.org/10.1176/APPI.NEUROPSYCH.13030064 Pastuszczak M, Zeman J, Jaworek AK, Wojas-Pelc A (2013) Cerebrospinal Fluid Abnormalities in HIV-Negative Patients with Secondary and Early Latent Syphilis and Serum VDRL ≥ 1:32. Indian J Dermatology 58(4):325. https://doi.org/10.4103/0019-5154.113941 Simon RP (1985) Neurosyphilis. Arch Neurol 42(6):606–613. https://doi.org/10.1001/ARCHNEUR.1985.04060060112021 Marra CM, Gary DW, Kuypers J, Jacobson MA (1996) Diagnosis of Neurosyphilis in Patients Infected with Human Immunodeficiency Virus Type 1. J Infect Dis 174(1):219–221. https://doi.org/10.1093/INFDIS/174.1.219 Marra CM (2007) Déjà Vu all over again: When to perform a lumbar puncture in HIV-infected patients with syphilis. Sex Transm Dis 34(3):145–146. https://doi.org/10.1097/01.OLQ.0000251204.18648.15 Ghanem KG (2010) REVIEW: Neurosyphilis: A Historical Perspective and Review. CNS Neurosci Ther 16(5):e157. https://doi.org/10.1111/J.1755-5949.2010.00183.X Spudich SS, Nilsson AC, Lollo ND, Liegler TJ, Petropoulos CJ, Deeks SG, Paxinos EE, Price RW (2005) Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC Infect Dis. 5 https://doi.org/10.1186/1471-2334-5-98 Lin L-R, Lin D-H, Tong M-L, Liu L-L, Fan J-Y, Zhu X-Z, Gao K, Chen M-J, Zheng W-H, Zhang H-L, Li S-L, Lin H-L, Lin Z-F, Niu J-J, Yang T-C (2016) Macrophage migration inhibitory factor as a novel cerebrospinal fluid marker for neurosyphilis among HIV-negative patients. https://doi.org/10.1016/j.cca.2016.10.018 Tong ML, Liu LL, Zeng YL, Zhang HL, Liu GL, Zheng WH, Dong J, Wu JY, Su YH, Lin LR, Yang TC (2013) Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom. Diagn Microbiol Infect Dis 75(4):377–380. https://doi.org/10.1016/J.DIAGMICROBIO.2013.01.013 Liu LL, Zhang HL, Huang SJ, Liu L, Tong ML, Lin LR, Chen YY, Xi Y, Guo XJ, Zhang YF, Zhang Q, Zheng WH, Chen FY, Jiang J, Yang TC (2013) Assessing cerebrospinal fluid abnormalities in neurosyphilis patients without human immunodeficiency virus infection. Int Immunopharmacol 17(4):1120–1124. https://doi.org/10.1016/J.INTIMP.2013.10.008 Klein M, Angstwurm K, Esser S, Hahn K, Maschke M, Scheithauer S, Schoefer H, Sturzenegger M, Wildemann B, Weber J (2020) German guidelines on the diagnosis and treatment of neurosyphilis. Neurol Res Pract 2020 2(1):1–9. https://doi.org/10.1186/S42466-020-00081-1 de Almeida SM, Kussen GB, Cogo LL, Nogueira K (2022) Cerebrospinal fluid lactate as a predictive biomarker for tuberculous meningitis diagnosis. Diagnosis, Dec 8;10(2):130–139. 10.1515/dx-2022-0102 . PMID: 36476307 Marks M, Lawrence D, Kositz C, Mabey D (2018) Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review. Sex Transm Infect 94(8):585–588. https://doi.org/10.1136/SEXTRANS-2018-053666 Ramachandran PS, Wilson MR (2020) Metagenomics for neurological infections — expanding our imagination. Nat Reviews Neurol 2020 16(10):547–556. https://doi.org/10.1038/s41582-020-0374-y Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigure1.docx.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 16 Feb, 2024 Reviews received at journal 13 Feb, 2024 Reviewers agreed at journal 16 Jan, 2024 Reviewers invited by journal 15 Jan, 2024 Editor assigned by journal 15 Jan, 2024 Submission checks completed at journal 28 Dec, 2023 First submitted to journal 27 Nov, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3673645","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264076653,"identity":"0b1c8f41-d2bc-4751-b6d9-2fd6dde7280d","order_by":0,"name":"Sérgio Monteiro de Almeida","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYLCCBBDB3sDwAcYmUgvPAcYZxGsBA4kEIrXIt/c+fvGggiGaf+Ybw+bCPQx55g0EtBicOW5mkXCGIXfG7RzD5hnPGIplDhDSIpHGZpDYxpDbcDvH/DHPAYbEGQQdNv8ZRMv8m2cMm4nSwnCDjfkBSMuGGzxEajE4k8bGkHBGInfjmbTC5hkHJIolCDqs/Rjzxx8VNrnzjh/e2FxwwCaPoBYgYAMqgqhjhjEIAeYPcBZR6kfBKBgFo2DEAQByGUEnYS0D9wAAAABJRU5ErkJggg==","orcid":"","institution":"Federal University of Paraná","correspondingAuthor":true,"prefix":"","firstName":"Sérgio","middleName":"Monteiro","lastName":"de Almeida","suffix":""},{"id":264076655,"identity":"74b73177-3fd0-4c59-acf5-4080d05b58c4","order_by":1,"name":"José Tresoldi Neto","email":"","orcid":"","institution":"Federal University of Paraná","correspondingAuthor":false,"prefix":"","firstName":"José","middleName":"Tresoldi","lastName":"Neto","suffix":""},{"id":264076658,"identity":"b7c5687f-361f-4a36-85ca-cf3645c484b4","order_by":2,"name":"Amanda Rocha","email":"","orcid":"","institution":"Federal University of Paraná","correspondingAuthor":false,"prefix":"","firstName":"Amanda","middleName":"","lastName":"Rocha","suffix":""},{"id":264076660,"identity":"65f1bb76-1cbc-4723-a347-31c6bc9af162","order_by":3,"name":"Ana Medeiros","email":"","orcid":"","institution":"Federal University of Paraná","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"Medeiros","suffix":""},{"id":264076661,"identity":"45c471e8-8a19-48a9-8622-63482c6e3bfd","order_by":4,"name":"Debora Gonçalves","email":"","orcid":"","institution":"Federal University of Paraná","correspondingAuthor":false,"prefix":"","firstName":"Debora","middleName":"","lastName":"Gonçalves","suffix":""},{"id":264076662,"identity":"1bb1c219-ce25-4e7a-b0b9-5d9a43b58869","order_by":5,"name":"Fausto Guimarães","email":"","orcid":"","institution":"Federal University of Paraná","correspondingAuthor":false,"prefix":"","firstName":"Fausto","middleName":"","lastName":"Guimarães","suffix":""}],"badges":[],"createdAt":"2023-11-27 19:47:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3673645/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3673645/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49092861,"identity":"d64cfa4d-3e68-41f3-bfe2-790f05a42fe1","added_by":"auto","created_at":"2024-01-03 02:09:24","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":681242,"visible":true,"origin":"","legend":"\u003cp\u003eStandards for Reporting of Diagnostic Accuracy Studies diagram indicating the flow chart for selection of participants for the validation study of cerebrospinal fluid (CSF) total protein, CSF WBC, or CSF lactate (index tests) as adjunct parameters for the diagnosis of neurosyphilis (NS) in CSF samples.\u003c/p\u003e\n\u003cp\u003eA total of 5,640 CSF reports on CSF RPR between December 2005 and August 2021 were analyzed. Of these, 5,404 samples were excluded based on the following criteria: no syphilis investigation in serum, samples of newborns, prospective samples, other defined causes that explain the neurological symptoms, presence of red blood cells (RBC) \u0026gt;200 cells/mm³[Izzat et al. 1971], syphilis serological scar defined as serum RPR results ≤ 1:4 in participants with a previous history of syphilis treatment [Rotta 2005], investigation of SS negative, or insufficient data. A total of 236 participants were included in the study and classified as people with HIV (PWH) and people without HIV (PWoH), and categorized into five subgroups: confirmed NS (G1)*; presumptive NS (G2); systemic syphilis (SS) (G3); PWH without SS and NS (G4); this group included participants with the following diagnoses: chronic headache (n=2), psychogenic condition (n=2), cardiac insufficiency (n=1), and unspecified disease caused by HIV (n = 5); and negative control (G5), which included PWoH without SS and NS with headache (n=33), respiratory failure (n=6), unspecified anemia (n=4), elective cesarean delivery (n=2), cardiopathy (n=7), gastrointestinal abnormality (n=6), intoxication (n=3), rotator cuff syndrome (n=2), and others (n=9).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3673645/v1/d3da1067a73cfe773492a373.jpeg"},{"id":49092859,"identity":"511ae6d2-b1f3-49ff-8cdb-44e1dc9c97b4","added_by":"auto","created_at":"2024-01-03 02:09:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":148756,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots of CSF total protein (mg/dL) and CSF white blood cells count (WBC, cells/mm³) comparing between syphilis and neurosyphilis groups in PWH and PWoH\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA and B. \u003c/strong\u003eCSF total protein (mg/dL) in PWH and PWoH. Other comparisons:\u003cstrong\u003e \u003c/strong\u003ePWH-G3 vs. G5 (p = 0.0330), PWH-G1 vs. PWH-G3 (p = 0.0004), PWH-G2 vs. PWH-G3 (p = 0.0094), PWH-G4 vs. negative control (G5) (p= 0.136), PWoH-G2 vs. PWoH-G3 (p = 0.0001), PWoH-G1 vs. PWoH-G3 (p \u0026lt; 0.0001), PWoH-G1 vs. PWoH-G2 (p = 0.0437), and PWoH-G3 vs. G5 (p= 0.081).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC and D. \u003c/strong\u003eCSF WBC count (cells/mm³) in PWH and PWoH\u003cstrong\u003e. \u003c/strong\u003eOther comparisons:\u003cem\u003e\u003cstrong\u003e \u003c/strong\u003e\u003c/em\u003ePWH-G1 vs. PWH-G3 (p \u0026lt; 0.0001), PWH-G2 vs. PWH-G3 (p = 0.003), PWH-G4 vs. negative control (G5) (p= 0.265), PWoH-G1 vs. PWoH-G3 (p = 0.030), and PWH-G2 vs. PWoH-G2 (p= 0.048).\u003c/p\u003e\n\u003cp\u003eBoxes show the medians and interquartile ranges and whiskers indicate the maximum and minimum values. Dots indicate the number of individuals in each group.\u003c/p\u003e\n\u003cp\u003eThe light blue dashed line represents the CSF total protein (A and B) or WBC (C and D) reference values.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE.\u003c/strong\u003e Spearman's correlation between CSF RPR titers and CSF total protein (mg/dL) in PWoH in the confirmed NS group, ρ = 0.551, p = 0.012. There was no correlation in PWH group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF.\u003c/strong\u003e Spearman's correlation between CSF RPR titers and CSF WBC (cells/mm³) in PWoH in the confirmed NS group, ρ = 0.478, p = 0.033. There was no correlation in PWH group.\u003c/p\u003e\n\u003cp\u003eCorrelation coefficients (\u003cem\u003er\u003c/em\u003e) were estimated using Spearman’s rank-order method; results are shown in \u003cem\u003er\u003c/em\u003e 95% confidence interval [CI]).\u003c/p\u003e\n\u003cp\u003eThere was no correlation between CSF and serum RPR titers in PWH or PWoH (ρ =-0.385, p = 0.103; ρ =-0.267, p= 0.285, respectively). The absence of correlation of CSF and serum RPR titers in PWH or PWoH, corroborates previous research concerning the greater accuracy of CSF nontreponemal antibody assays than of treponemal ones to diagnose NS [Wharton et al. 1990; Marra 2015] in both PWH and PWoH.\u003c/p\u003e\n\u003cp\u003eIn PWH, CSF RPR titers did not correlate with peripheral blood HIV RNA, CD4\u003csup\u003e+\u003c/sup\u003e count, CD8\u003csup\u003e+\u003c/sup\u003e count, or CD4\u003csup\u003e+\u003c/sup\u003e/CD8\u003csup\u003e+\u003c/sup\u003e ratio (all p \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003ePWH, people with HIV; PWoH, people without HIV; G1, Confirmed NS; G2, Presumptive NS; G3, systemic syphilis (SS); G4, PWH without SS and/or NS; G5, Negative control.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3673645/v1/b9c795a6c9994919fd792004.png"},{"id":49093674,"identity":"9e3da841-6c00-4715-ae71-3bb9e6368789","added_by":"auto","created_at":"2024-01-03 02:17:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":210669,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver-operating characteristic (ROC) curves of CSF total protein and WBC count as adjunct biomarkers to diagnose neurosyphilis, in PWH and PWoH.\u003c/p\u003e\n\u003cp\u003ePWH (purple), PWoH (red), and total (green).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003eROC curve of CSF total protein (mg/dL) as single test to diagnose confirmed NS, showing higher AUC in PWoH (AUC = 0.91) than in PWH (AUC = 0.79); the best cutoff point of CSF total protein (mg/dL) for our cohort of participants was 39 mg/dL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB. \u003c/strong\u003eROC curve of CSF total protein (mg/dL) as single test to diagnose confirmed NS and presumptive NS, showing a higher AUC in PWH (AUC = 0.84) than in PWoH (AUC = 0.65).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC. \u003c/strong\u003eROC curve of CSF WBC (cells/mm³) as single test to diagnose confirmed NS, showing a higher AUC in PWH (AUC = 0.88) than in PWoH (AUC = 0.68);\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD. \u003c/strong\u003eROC curve of CSF WBC (cells/mm³) as single test to diagnose confirmed NS and presumptive NS, showing a higher AUC in PWH (AUC = 0.84) than in PWoH (AUC = 0.65).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE.\u003c/strong\u003e ROC curve of CSF total protein \u0026gt; 45 mg/dL and/or CSF WBC \u0026gt; 5 cells/mm³ combined tests to diagnose confirmed NS, showing a higher AUC in PWH (AUC = 0.86) than in PWoH (AUC = 0.67).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF.\u003c/strong\u003e ROC curve of CSF total protein \u0026gt; 45 mg/dL and/or CSF WBC \u0026gt; 5 cells/mm³ combined tests to diagnose confirmed NS and presumptive NS, showing a higher AUC in PWH (AUC = 0.82) than in PWoH (AUC = 0.62).\u003c/p\u003e\n\u003cp\u003ePWH, people with HIV; PWoH, people without HIV; G1, Confirmed NS; G2, Presumptive NS; G3, Systemic syphilis; G4, PWH without SS and/or NS; G5, Negative control. Area under the curve, AUC (95% confidence interval), p value.\u003c/p\u003e\n\u003cp\u003eThe high AUC indicates that CSF TP and CSF WBC are suitable parameters to diagnose confirmed and presumptive NS. In PWH, CSF WBC count was a better diagnostic parameter; on the other hand, in PWoH, CSF TP was better.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3673645/v1/6269d9a200fdc37317812b61.png"},{"id":49093844,"identity":"2fc16d59-d778-42b7-9236-e45336da1ee5","added_by":"auto","created_at":"2024-01-03 02:25:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":156695,"visible":true,"origin":"","legend":"\u003cp\u003eFagan's Nomograms of CSF total protein or CSF WBC, as single tests, with different cutoffs points, to calculate the posterior probability for a positive and for a negative test to diagnose confirmed neurosyphilis in PWH and PWoH.\u003c/p\u003e\n\u003cp\u003ePositive tests are represented by a solid line, and negative tests are represented by a dashed line. PWH: people with HIV; PWoH: people without HIV; G1, confirmed NS; G2, presumptive NS; G3, systemic syphilis; G4, PWH without SS and/or NS; G5, negative control; Odds=Probability/(1-Probability); Posterior odds: Prior odds × LR; LR: likelihood ratio; +LR = Sensitivity / (1 - specificity); -LR = (1 - sensitivity) / specificity. For PWH (G1vsG3+4), the prior probability was 45% (0.8), while for PWoH (G1vsG3+5), the prior probability was 18% (0.2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA.\u003c/strong\u003e Among PWH, for CSF WBC \u0026gt; 5 cells/mm³ (blue line), for a positive test: LR+ 15 (95% CI 2.07–105), posterior probability (odds) 92% (12.2) (95% CI 63–99), around 1 in 1.1 with positive test had confirmed NS; for a negative test: LR- 0.47 (95% CI 0.30–0.75), posterior odds 28% (0.4) (95% CI 20–38), around 1 in 1.4 with negative test were not with confirmed NS. For CSF WBC\u0026gt; 10 cells/mm³ (green line), for a positive test: LR+ infinite (95% CI 1.42–377), posterior odds 100% (814815.3) (95% CI 54–100), around 1 in 1.0 with positive test had NS confirmed; for a negative test: LR- 0.59 (95% CI 0.42–0.85), posterior odds 32% (0.5) (95% CI 25–41), around 1 in 1.5 with negative test were not with confirmed NS. For CSF WBC\u0026gt;20 cells/mm³ (pink line), for a positive test: LR+ infinite (95% CI 1.10–303), posterior odds 100% (814815.3) (95% CI 47–100), around 1 in 1.0 with positive test had NS confirmed; for a negative test: LR- 0.68 (95% CI 0.51–0.92), posterior odds 36% (0.6) (95% CI 29–43), around 1 in 1.6 with negative test were not with confirmed NS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB.\u003c/strong\u003e Among PWoH, for CSF WBC\u0026gt; 5 cells/mm³ (blue line), for positive test: LR+ 7.75 (95% CI 2.01–30), posterior odds 62% (1.7) (95% CI 30–87), around 1 in 1.6, with a positive test having NS confirmed; for a negative test, LR- 0.78 (95% CI 0.60–1), posterior odds 14% (0.2) (95% CI 11–18), around 1 in 1.2, with a negative test, were not with NS confirmed. For CSF WBC 10\u0026gt;cells/mm³ (green line), for a positive test: LR+ 23 (95% CI 2.87–188), posterior odds 83% (4.9) (95% CI 38–98), around 1 in 1.2 with positive test had NS confirmed; For a negative test: LR- 0.76 (95% CI 0.59–0.98), posterior odds 14% (0.2) (95% CI 11–17), around 1 in 1.2 with negative test were not with NS confirmed. For CSF WBC\u0026gt;20 cells/mm³ (pink line), for a positive test: LR+ infinite (95% CI 1.12–449), posterior odds 100% (215053.3) (95% CI 19–100), around 1 in 1.0 with positive test had NS confirmed; for a negative test: LR- 0.90 (95% CI 0.76–1.04), posterior odds 16% (0.2) (95% CI 14–18), around 1 in 1.2 with negative test were not with NS confirmed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC.\u003c/strong\u003e Among PWH, for CSF total protein \u0026gt; 45 mg/dL (red line), for a positive test: LR+ 2.61 (95% CI 1.40–4.87), posterior odds 68% (2.1) (95% CI 53–80), around 1 in 1.5 with positive test had NS confirmed; for the negative test: LR- 0.32 (95% CI 0.14–0.72), posterior odds 21% (0.3) (95% CI 10–37), around 1 in 1.3 with negative test were not with NS confirmed. For CSF total protein\u0026gt;39 mg/dL (purple line), for positive test: LR+ 2.32 (95% CI 1.30–4.14), posterior odds 65% (1.9) (95% CI 51–77), around 1 in 1.5 with positive test had NS confirmed; for negative test: LR- 0.34 (95% CI 0.15–0.77), posterior odds 22% (0.3) (95% CI 11–39), around 1 in 1.3 with negative test were not with NS confirmed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD.\u003c/strong\u003e Among PWoH, for CSF total protein\u0026gt; 45 mg/dL (red line), for a positive test: LR+ 15 (95% CI 5.50–42), posterior odds 76% (3.2) (95% CI 54–90), around 1 in 1.3 with positive test had NS confirmed; for a negative test: LR- 0.37 (95% CI 0.20–0.67), odds 7% (0.1) (95% CI 4–13), around 1 in 1.1 with negative test were not with NS confirmed. For CSF total protein \u0026gt;39 mg/dL (purple line), for positive test: LR+ 5.65 (95% CI 3.37–9.47), posterior odds 55% (1.2) (95% CI 42–67), around 1 in 1.8 with positive test had NS confirmed; For negative test: LR- 0.18 (95% CI 0.06–0.50), posterior odds 4% (0.0) (95% CI 1–10), around 1 in 1.0 with negative test were not with NS confirmed.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3673645/v1/195c718ffa09a3d8c6a0a439.png"},{"id":49094192,"identity":"f16c2c14-1d70-444e-b273-1da8c18b5202","added_by":"auto","created_at":"2024-01-03 02:41:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1059438,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3673645/v1/3d903be0-dcc4-4b2f-bb18-19d778d1b5c4.pdf"},{"id":49094071,"identity":"120acf6f-6582-4caf-8fc5-a985d533d5de","added_by":"auto","created_at":"2024-01-03 02:33:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":417546,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.docx.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3673645/v1/e6f7ff6bf4be0bff2d3dfaa5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cerebrospinal fluid biomarkers of symptomatic neurosyphilis in people with HIV compared with uninfected individuals","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eNeurosyphilis (NS) diagnosis remains challenging as no gold standard tests are available [Guarner et al. 2015; Yu et al. 2021]. A reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test confirms the diagnosis of NS in a patient with a reactive serum treponemal test. However, a nonreactive test cannot exclude NS diagnosis. Combining nontreponemal assays with the analysis of CSF characteristics improves NS diagnostic accuracy [Dumaresq et al. 2013; Salamano et al. 2016].\u003c/p\u003e \u003cp\u003eCSF-VDRL has more false positives and negatives in people with HIV (PWH) [Feraru et al. 1990]; therefore, diagnosis of NS in PWH may additionally require the identification of increased CSF white blood cell (WBC) count and CSF total protein (TP).\u003c/p\u003e \u003cp\u003eThis study aimed to expand on previous studies by measuring the diagnostic clinical performance characteristics (DCPC) of CSF TP, WBC count, and lactate (LA) with different cutoff points as adjunct predictive biomarkers for confirmed or presumptive symptomatic NS, and the impact of HIV infection on them.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1 Study design and participants\u003c/h2\u003e\n \u003cp\u003eThis was a retrospective analysis of medical reports and laboratory data collected from electronic medical charts of the Hospital de Cl\u0026iacute;nicas, Universidade Federal do Paran\u0026aacute; (HC-UFPR), Curitiba, Paran\u0026aacute;, Brazil. All CSF samples included in this study were collected for clinical purpose via lumbar puncture (LP), between December 2005 and August 2021.\u003c/p\u003e\n \u003cp\u003e5,640 CSF reports, all with Rapid Plasm Reagin (RPR) assay analyzed in CSF, were obtained. The flow chart for participant selection is showed in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The 236 participants included were classified as PWH or people without HIV (PWoH) [Minist\u0026eacute;rio da Sa\u0026uacute;de 2018]. They were further classified into five subgroups according to the diagnosis of systemic syphilis (SS) [Minist\u0026eacute;rio da Sa\u0026uacute;de 2011; Minist\u0026eacute;rio da Sa\u0026uacute;de 2022] and NS [Wharton et al. 1990; French et al. 2009; Workowski and Bolan 2015] (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e):\u003c/p\u003e\n \u003cp\u003e- G.1 Confirmed NS (n\u0026thinsp;=\u0026thinsp;42): positive CSF RPR [Zhu et al. 2014; Boog et al. 2021], serological diagnosis of SS positive, and neurological symptoms suggestive of NS [Gonzalez et al. 2019; Marra 2015; Ropper 2019].\u003c/p\u003e\n \u003cp\u003e- G.2 Presumptive NS (n\u0026thinsp;=\u0026thinsp;74): negative CSF RPR, serological diagnosis of SS positive, and neurological symptoms suggestive of NS, without an alternate diagnosis to account for these.\u003c/p\u003e\n \u003cp\u003e- G.3 SS (n\u0026thinsp;=\u0026thinsp;38), serological diagnosis of SS, absence of neurological symptoms suggestive of NS, and negative CSF RPR.\u003c/p\u003e\n \u003cp\u003e- G.4 PWH without SS and NS (n\u0026thinsp;=\u0026thinsp;10), positive HIV diagnosis [Minist\u0026eacute;rio da Sa\u0026uacute;de 2018], absence of CNS opportunistic infection defined by negative CSF standard microbiological methods and medical history, absence of SS and NS.\u003c/p\u003e\n \u003cp\u003e- G.5 Negative control (n\u0026thinsp;=\u0026thinsp;72), HIV negative, SS or NS investigation negative, no neurological symptoms other than headache, absence of defined or suspected infection.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 CSF and peripheral blood samples\u003c/h2\u003e\n \u003cp\u003eTwo treponemal assays, FTA-ABS [Larsen et al. 1995] and Chemiluminescent Microparticle Immuno Assay (CMIA), were performed to qualitatively detect antibodies against \u003cem\u003eTreponema pallidum\u003c/em\u003e (Alinity i. Abbott, Germany). The nontreponemal antibody assay used was RPR (BR\u0026Aacute;S, Laborclin, Brazil). Tests were performed according to the manufacturer\u0026rsquo;s instructions.\u003c/p\u003e\n \u003cp\u003eCSF TP was quantified using benzethonium chloride, GL in CSF and plasma using hexokinase/G-6-PDH (both from Architect, Abbott, IL, USA), and CSF LA using amperometry (RAPID Point 500, Siemens, New York City, NY, USA) [de Almeida et al. 2020]. Total CSF WBC count was quantified in fresh uncentrifuged CSF in a Fuchs-Rosenthal chamber. Differential WBC counts were performed using standard laboratory methods. Standard microbiological tests were used to examine CSF samples for bacteria, fungi, and viruses [Deisenhammer et al. 2006].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.3 Statistical analysis\u003c/h2\u003e\n \u003cp\u003eData are presented as median and interquartile range (IQR) or number (n, %), as appropriate. Categorical variables were compared among the groups using the Chi-square test or Fisher\u0026rsquo;s exact test. Continuous variables were compared using the Mann-Whitney or Kruskal-Wallis tests for non-parametric data, as appropriate. We estimated the correlation coefficients (r\u003csub\u003es\u003c/sub\u003e) of CSF and serum RPR titer, CSF WBC count, CSF TP, HIV infection characteristics (current age, age at the beginning of the infection, plasma HIV RNA), and cell immunity characteristics (current CD4\u003csup\u003e+\u003c/sup\u003e, CD8\u003csup\u003e+\u003c/sup\u003e, CD4\u003csup\u003e+\u003c/sup\u003e/CD8\u003csup\u003e+\u003c/sup\u003e ratio) using Spearman\u0026rsquo;s rank-order method. The results were considered significant at 5% alpha level.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e2.4 Diagnostic Clinical Performance Characteristics (DCPC)\u003c/h2\u003e\n \u003cp\u003eThe DCPC of CSF TP and/or WBC count (index tests) for the diagnosis of NS was calculated using confirmed or presumptive NS defined by positive CSF RPR and the presence of clinical characteristics [Wharton et al. 1990] as the reference gold standard method. The DCPC included sensitivity, specificity, accuracy (efficiency), positive and negative predictive values (PPV and NPV), Youden index, positive and negative clinical utility index (CUI\u0026thinsp;+\u0026thinsp;and CUI\u0026minus;) [Mitchell 2008; Mitchell 2011], positive and negative likelihood ratios (LR\u0026thinsp;+\u0026thinsp;and LR\u0026minus;), diagnostic odds ratio (DOR) [Akobeng 2007a; Glas et al. 2003; McGee 2002], Matthews correlation coefficient (MCC) [Matthews 1975]. The post-test probabilities were calculated using Bayes\u0026rsquo; theorem, with pre-test probabilities and likelihood ratios plotted on Fagan\u0026apos;s nomogram [Sackett and Haynes 2002; TJ 1975]. The receiver operating characteristic (ROC) curve was used to determine the cutoff value associated with the highest distinction between confirmed and/or presumptive NS (G1 and/or G2, respectively) and each of the other categories, including negative controls (G3, G4, and G5). The Youden index (J) was defined for all points in the ROC curve. The maximum value of the index was used as a criterion to select the optimal cut-off point of a diagnostic test, the area under the ROC curve (AUC) was analyzed, and the difference between the curve and the baseline (random line) was calculated [Akobeng 2007a; Akobeng 2007b].\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003eThe epidemiological, CSF characteristics of the samples distributed according to PWH and PWoH groups, clinical signs and symptoms are presented in Tables \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Among PWH, the groups confirmed NS, presumptive NS, SS, and PWH without SS and/or NS were comparable for PB HIV RNA (log), PB CD4\u003csup\u003e+\u003c/sup\u003e lymphocytes (cells/mm\u0026sup3;), PB CD8\u003csup\u003e+\u003c/sup\u003e lymphocytes (cells/mm\u0026sup3;), PB CD4\u003csup\u003e+\u003c/sup\u003e/CD8\u003csup\u003e+\u003c/sup\u003e, and participants on antiretroviral therapy (ART) (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Among PWH with confirmed and presumptive NS, PB HIV RNA levels were higher and PB CD4\u003csup\u003e+\u003c/sup\u003e counts were lower than those in the PWH without SS and NS groups (G4).\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic, HIV infection characteristics, and CSF biochemical and cytological characteristics of the samples distributed in the groups PWH and PWoH\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003ePWH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003ePWoH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePWH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePWoH\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA-G1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB-G2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC-G3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-G4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eE-G1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eF-G2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG-G3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eH-G5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.00 (77.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.00 (81.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (76.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.00 (50.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.00 (75.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.00 (56.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.00 (47.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.00 (33.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.00 (35.00; 48.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.00 (36.00; 43.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.00 (32.00; 58.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.00 (34.00; 49.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.00 (50.50; 63.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.00 (52.00; 75.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.00 (41.00; 71.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.00 (34.00; 59.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF RBC, cells/mm\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.25 (0.53; 19.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.90 (0.45; 21.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.10 (0.75; 18.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.30; 2.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.70 (0.60; 32.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.85 (0.90; 23.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00 (0.30; 15.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.80 (0.30; 9.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2907\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2145\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF WBC, cells/mm\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.60 (1.28; 30.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.60 (0.90; 6.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (0.30; 1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45 (0.23; 1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.75 (0.38; 12.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.20 (0.60; 2.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (0.30; 1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90 (0.30; 1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0142\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u0026sup3;, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (54.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (37.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (10.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (25.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (13.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (2.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0149\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLynphocytes %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.00 (93.00; 98.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91.50 (85.75; 96.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.00 (84.50; 98.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91.50 (80.25; 95.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.00 (95.00; 95.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2731\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF Glucose, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.00 (38.25; 59.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.50 (46.25; 61.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.00 (50.00; 64.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.00 (48.25; 68.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.50 (53.00; 67.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.50 (58.75; 79.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.00 (53.50; 77.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.50 (57.00; 74.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0622\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2808\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF Total Protein, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.30 (43.83; 84.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.00 (39.63; 65.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.60 (28.20; 40.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.25 (22.85; 62.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.10 (40.43; 68.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.90 (36.05; 54.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.60 (25.00; 38.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.65 (22.40; 33.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF Total Protein\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (77.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (62.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (17.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (50.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (65.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (48.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (14.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF Lactate, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.90 (1.56; 2.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.70 (1.40; 2.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.40 (1.30; 1.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.40 (1.33; 1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64 (1.52; 2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.81 (1.60; 2.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.78 (1.64; 2.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.70 (1.50; 1.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3731\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHIV RNA, log10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.60 (3.25; 5.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.82 (3.57; 5.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.79 (1.70; 4.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.90 (1.70; 4.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1440\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHIV RNA\u0026thinsp;\u0026lt;\u0026thinsp;50 copies/mL, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/12 (16.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/8 (12.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/14 (42.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/9 (33.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCD4, cells/mm\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e174.00 (38; 320)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e135.00 (80.00; 327.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e192.50 (99.00; 472.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e121.00 (36.50; 698.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCD4\u0026thinsp;\u0026gt;\u0026thinsp;500 cells/mm\u0026sup3;, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/11 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/8 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/12 (16.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/9 (33.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCD8. cells/mm\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e877.50 (386.00; 1945.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e832.00 (67.00; 940.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e669.00 (386.30; 1094.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1057.00 (690.00; 1159.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCD4/CD8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.15 (0.08; 0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.20 (0.06; 0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.28 (0.15; 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11 (0.10; 0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eon ART, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16/22 (72.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10/16 (62.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11/17 (64.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/10 (60.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRegular use of ART, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/13 (46.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/14 (42.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/12 (58.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/6 (66.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7995\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003eData is presented as median (interquartile) or number (n, %) as appropriate.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003eRBC, red blood cell; WBC, white blood cell; PWH, people with HIV; PWoH, people without HIV; ART, antiretroviral therapy; NS, neurosyphilis.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003eG1, confirmed NS; G2, presumptive NS; G3, systemic syphilis; G4, PWH without SS and NS; G5, negative control.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003ep values were calculated with chi-square or Kruskal-Wallis tests as appropriate.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003e\u003csup\u003ea\u003c/sup\u003e p values for the comparison of the PWH groups, A vs. B vs. C vs. D.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003e\u003csup\u003eb\u003c/sup\u003e p values for the comparison of the PWoH groups, E vs. F vs. G vs. H.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003eSyphilis infection is known to have a negative impact on immune recovery during HIV infection and an increase in HIV VL in the peripheral blood and CSF [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSigns and symptoms of participants with confirmed and presumptive NS, in PWH and PWoH.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePWH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePWoH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSigns and Symptoms\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea-G1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb-G2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003cp\u003ea vs. b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec-G1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ed-G2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003cp\u003ec vs. d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003cp\u003ea vs. c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003cp\u003eb vs. d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParesis/plegia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (31.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (31.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (34.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDysarthria/aphasia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (18.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (31.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConfusion/agitation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (18.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003espasticity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (13.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeuropsychiatric\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (13.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eheadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (31.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (8.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyperreflexia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePupillary changes\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (10.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eataxic gait\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (9.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmaurosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (5.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNystagmus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003elabial commissure deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (6.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTremor\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (4.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (3.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiplopia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSeizure\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePapilledema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypoacusis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003edizziness/vertigo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (10.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBradykinesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ePWH, people with HIV; PWoH, people without HIV; NS, neurosyphilis;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eG1, confirmed NS; G2, presumptive NS. The participants presented more than one sign or symptom.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003e\u003csup\u003e1\u003c/sup\u003ePWH-G1, memory impairment (n\u0026thinsp;=\u0026thinsp;2), visual hallucinations (n\u0026thinsp;=\u0026thinsp;1); PWoH-G1, memory impairment (n\u0026thinsp;=\u0026thinsp;1), behavior alteration (n\u0026thinsp;=\u0026thinsp;2); PWH-G2, depression (n\u0026thinsp;=\u0026thinsp;1), psychosis (n\u0026thinsp;=\u0026thinsp;1), memory impairment (n\u0026thinsp;=\u0026thinsp;1); PWoH-G2, dementia (n\u0026thinsp;=\u0026thinsp;3), personality change (n\u0026thinsp;=\u0026thinsp;3), delusions (n\u0026thinsp;=\u0026thinsp;2), depression (n\u0026thinsp;=\u0026thinsp;1), hallucinations (n\u0026thinsp;=\u0026thinsp;1), memory impairment (n\u0026thinsp;=\u0026thinsp;3), psychosis (n\u0026thinsp;=\u0026thinsp;1).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003e\u003csup\u003e2\u003c/sup\u003ePWH-G1, fixed mydriasis (n\u0026thinsp;=\u0026thinsp;1), anisocoria (n\u0026thinsp;=\u0026thinsp;1).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003e\u003csup\u003e3\u003c/sup\u003ePWH-G1, rest tremor (n\u0026thinsp;=\u0026thinsp;1); PWoH-G2, delirium tremens (n\u0026thinsp;=\u0026thinsp;1), kinetic and postural tremor (n\u0026thinsp;=\u0026thinsp;1).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003e\u003csup\u003e4\u003c/sup\u003ePWH-G2, generalized tonic seizures (n\u0026thinsp;=\u0026thinsp;2), unspecified seizures (n\u0026thinsp;=\u0026thinsp;1). PWoH-G2, generalized tonic-clonic seizure (n\u0026thinsp;=\u0026thinsp;1).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 CSF WBC\u003c/h2\u003e\n \u003cp\u003eAmong PWH, the number of CSF samples with elevated CSF WBC (\u0026gt;\u0026thinsp;5 cell/mm\u003csup\u003e3\u003c/sup\u003e) was comparable between the confirmed and presumptive NS groups [12 (55.00%) and 6 (38.00%), respectively, p\u0026thinsp;=\u0026thinsp;0.342], higher in confirmed NS when compared with the PWH without SS and/or NS group (G4, p\u0026thinsp;=\u0026thinsp;0.024), and comparable between presumptive NS and G4 (p\u0026thinsp;=\u0026thinsp;0.19). No increase in CSF WBC count was observed in the SS group (G3).\u003c/p\u003e\n \u003cp\u003eIn PWoH, the number of CSF samples with elevated CSF WBC (\u0026gt;\u0026thinsp;5 cell/mm\u003csup\u003e3\u003c/sup\u003e) was comparable between the confirmed and presumptive NS and SS groups [5 (25.00), 8 (13.79), and 1 (4.76), respectively, p\u0026thinsp;=\u0026thinsp;0.176; confirmed vs. presumptive NS groups, p\u0026thinsp;=\u0026thinsp;0.300]. Higher in the confirmed and presumptive NS groups than in the negative control group (G5) (p\u0026thinsp;=\u0026thinsp;0.005 and 0.024, respectively), and comparable between the SS and negative control group (G5) (p\u0026thinsp;=\u0026thinsp;0.540).\u003c/p\u003e\n \u003cp\u003eThe number of samples with elevated CSF WBC count was higher in PWH than in PWoH for the confirmed and presumptive NS subgroups, although this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.066 and 0.065, respectively) and was comparable for the SS groups (p\u0026thinsp;=\u0026thinsp;1.00).\u003c/p\u003e\n \u003cp\u003eThe confirmed NS group had a higher median CSF WBC count, regardless of PHW or PWoH. All comparisons of the confirmed or presumptive NS groups with the negative control group (G5) were p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe median CSF WBC counts were comparable between the confirmed and presumptive NS groups in PWH or PWoH (p\u0026thinsp;=\u0026thinsp;0.146 and 0.299, respectively).\u003c/p\u003e\n \u003cp\u003eComparing the confirmed or presumptive NS groups, showed that it was higher in the PWH than in the PWoH [for presumptive NS, p\u0026thinsp;=\u0026thinsp;0.048; although for confirmed NS, it was not significant (p\u0026thinsp;=\u0026thinsp;0.078)). The median CSF WBC counts in the SS groups were comparable between PWH and PWoH (p\u0026thinsp;=\u0026thinsp;0.910) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 CSF TOTAL PROTEIN\u003c/h2\u003e\n \u003cp\u003eAmong PWH, the number of CSF samples with CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL was comparable among the confirmed and presumptive NS [17 (77.00%) and 10 (66.00%), respectively, p\u0026thinsp;=\u0026thinsp;0.471] and higher in confirmed and presumptive NS when compared with the SS group (0.0003 and 0.013, respectively). However, both groups were comparable with the G4 group (0.217 and 0.689, respectively).\u003c/p\u003e\n \u003cp\u003eAmong PWoH, the number of CSF samples with CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL was comparable between confirmed and presumptive NS (p\u0026thinsp;=\u0026thinsp;0.299), increased in these groups compared with the SS group (p\u0026thinsp;=\u0026thinsp;0.001 and 0.008), and higher in confirmed NS, presumptive NS, and SS when compared with the negative control group (G5) (ps\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, \u0026lt; 0.0001, and 0.035, respectively).\u003c/p\u003e\n \u003cp\u003eThe confirmed NS group had higher median CSF TP, regardless of PWH or PWoH. All comparisons of the confirmed or presumptive NS groups with the negative control group (G5) were significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe median CSF TP was higher in the confirmed or presumptive NS groups in PWoH (p\u0026thinsp;=\u0026thinsp;0.044) but comparable in PWH (p\u0026thinsp;=\u0026thinsp;0.193).\u003c/p\u003e\n \u003cp\u003eComparing the groups between PWH and PWoH, the medians of CSF TP were comparable for confirmed NS, presumptive NS, and SS (P\u0026thinsp;=\u0026thinsp;0.493, 0.367, 0.063 respectively).\u003c/p\u003e\n \u003cp\u003eCorrelations of CSF TP and WBC count with CSF RPR titers in PWoH are shown in Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE and F.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 DCPC of CSF WBC count and TP\u003c/h2\u003e\n \u003cp\u003eThe DCPC of the CSF WBC count single test to diagnose confirmed or presumptive NS in PWH or PWoH is shown in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. For CSF WBC count, the AUC and MCC were higher in PWH than in PWoH. The higher the cutoff point of CSF WBC, the greater the specificity, LR+, LR-, and the lower the sensitivity. The DOR increases progressively with an increase in the cutoff point, indicating a greater chance of diagnosis. The MCC did not show significant variation between the different cutoff points, indicating that the data compared at each cutoff point had a similar correlation with the others (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical performance characteristics of CSF WBC count, as single test, with the cutoff points\u0026thinsp;\u0026gt;\u0026thinsp;5, \u0026gt;10, and \u0026gt;\u0026thinsp;20 cells/mm\u0026sup3;, as adjunct biomarkers to diagnose confirmed and presumptive neurosyphilis in PWH and PWoH.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePWH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePWoH\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCSF WBC (cells/mm\u0026sup3;)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1vs.G3\u0026thinsp;+\u0026thinsp;4\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2vs.G3\u0026thinsp;+\u0026thinsp;4\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u0026thinsp;+\u0026thinsp;2vs.G3\u0026thinsp;+\u0026thinsp;4\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1vs.G3\u0026thinsp;+\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2vs.G3\u0026thinsp;+\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u0026thinsp;+\u0026thinsp;2vs.G3\u0026thinsp;+\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1vs.G3\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2vs.G3\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u0026thinsp;+\u0026thinsp;2vs.G3\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;5 cells/mm\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrue Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.48 (25.63; 56.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.92 (10.75; 29.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.72 (18.93; 35.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.55 (32.21; 75.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.50 (15.20; 64.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.37 (30.98; 64.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00 (8.66; 49.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.79 (4.92; 22.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.67 (9.18; 26.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpecificity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.67 (91.69; 99.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.67 (91.69; 99.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.67 (91.69; 99.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.30 (81.03; 99.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.30 (81.03; 99.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.30 (81.03; 99.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.27 (92.24; 99.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.27 (94.23; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.27 (92.24; 99.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.14 (4.33; 34.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.68 (1.94; 16.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.02 (2.92; 22.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.73 (2.07; 104.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.12 (1.34; 76.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.79 (1.82; 90.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.17 (2.38; 35.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.06 (1.39; 18.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.11 (1.80; 20.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.48; 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.75; 0.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76 (0.68; 0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47 (0.30; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 (0.44; 0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 (0.40; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77 (0.60; 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 (0.80; 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86 (0.77; 0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.72 (6.11; 63.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.77 (2.13; 21.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.58 (3.60; 31.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.20 (3.58; 272.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.60 (1.66; 146.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.40 (2.88; 190.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.89 (2.57; 54.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.71 (1.45; 22.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.13 (1.96; 25.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33 (0.12; 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.15 (0.00; 0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24 (0.10; 0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.25; 0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32 (0; 0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45 (0.25; 0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16 (0.00; 0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10 (0; 0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14 (0.00; 0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80 (0.75; 0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 (0.59; 0.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56 (0.51; 0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70 (0.59; 0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70 (0.59; 0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54 (0.43; 0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 (0.81; 0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66 (0.61; 0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61 (0.55; 0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.95 (60.25; 92.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.78 (54.49; 91.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.57 (73.85; 95.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.31 (62.81; 98.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.71 (44.20; 97.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94.74 (71.87; 99.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.50 (30.18; 86.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.73 (46.41; 99.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.25 (56.09; 93.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.27 (78.30; 85.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.91 (63.28; 68.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.71 (54.89; 60.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.22 (62.05; 80.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.22 (63.85; 79.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.52 (48.79; 63.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.70 (84.68; 90.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.15 (60.87; 75.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.21 (59.73; 64.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccuracy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.10 (75.31; 87.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.01 (59.91; 73.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.29 (55.77; 68.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.55 (63.38; 88.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.42 (58.83; 86.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.69 (54.95; 78.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.15 (79.00; 91.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.45 (60.85; 75.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.83 (56.52; 70.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYouden\u0026rsquo;s index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37 (0.17; 0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16 (0.02; 0.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23 (0.11; 0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51 (0.13; 0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34 (-0.04; 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.12; 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22 (0.01; 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11 (-0.01; 0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14 (0.01; 0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77 (0.68; 0.86)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66 (0.58; 0.74)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70 (0.64; 0.77)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88 (0.77; 0.98)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78 (0.63; 0.93)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.74; 0.93)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68 (0.53; 0.83)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 (0.54; 0.72)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 (0.56; 0.73)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;10 cells/mm\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrue Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.33 (19.57; 49.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.11 (3.03; 16.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.24 (10.86; 25.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.91 (20.71; 63.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.50 (1.55; 38.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.95 (15.42; 45.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.00 (8.66; 49.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90 (1.91; 16.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.54 (5.41; 20.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpecificity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99.17 (95.44; 99.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99.17 (95.44; 99.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99.17 (95.44; 99.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (87.23; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (87.23; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (87.23; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98.92 (94.15; 99.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98.92 (94.15; 99.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98.92 (94.15; 99.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.00 (5.42; 295.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.73 (1.19; 79.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.69 (2.82; 151.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.25 (2.87; 188.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.41 (0.73; 55.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.73 (1.39; 82.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67 (0.54; 0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93 (0.86; 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.83 (0.77; 0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59 (0.42; 0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88 (0.73; 1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71 (0.58; 0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76 (0.59; 0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94 (0.87; 1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 (0.82; 0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.50 (7.51; 471.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.50 (1.24; 89.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.79 (3.27; 188.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.70 (2.09; 715.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.48 (0.43; 210.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.00 (1.29; 409.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.67 (3.35; 281.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.81 (0.74; 62.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.00 (1.49; 96.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31 (0.09; 0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07 (0.00; 0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16 (0.02; 0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.13; 0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13 (0.00; 0.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29 (0.06; 0.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 (0.00; 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.06 (0.00; 0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12 (0.00; 0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80 (0.76; 0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 (0.58; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 (0.50; 0.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68 (0.57; 0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66 (0.55; 0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.39; 0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 (0.81; 0.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.57; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (0.54; 0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.33 (65.50; 99.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.71 (42.42; 97.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.24 (73.18; 99.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.33 (38.16; 97.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.00 (31.42; 97.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.61 (37.99; 53.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.95 (77.42; 84.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.64 (62.01; 65.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.35 (53.25; 57.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.50 (59.46; 74.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.85 (61.58; 69.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.00 (44.94; 55.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.98 (82.63; 88.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.01 (61.29; 64.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.00 (53.82; 98.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccuracy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.10 (75.31; 87.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.43 (57.26; 71.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.90 (52.33; 65.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.47 (58.92; 85.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.44 (51.46; 80.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.46 (45.56; 70.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.84 (78.03; 91.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.58 (55.36; 71.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.14 (55.10; 59.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYouden\u0026rsquo;s index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33 (0.15; 0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.08 (-0.80; 0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16 (0.06; 0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.08; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13 (-0.11; 0.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29 (0.03; 0.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24 (0.03; 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05 (-0.04; 0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10 (0.00; 0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77 (0.68; 0.86)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66 (0.58; 0.74)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70 (0.64; 0.77)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88 (0.77; 0.98)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78 (0.63; 0.93)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.74; 0.93)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68 (0.53; 0.83)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 (0.54; 0.72)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 (0.56; 0.73)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;20 cells/mm\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrue Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.43 (10.30; 36.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.05 (0.84; 11.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.34 (5.46; 17.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.82 (13.86; 54.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.25 (0.16; 30.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.05 (9.55; 37.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.00 (1.23; 31.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.45 (0.42; 11.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.13 (1.41; 12.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpecificity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (96.97; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (96.97; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (96.97; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.0 (87.23; 100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (87.23; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (87.23; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (96.11; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (96.11; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00 (96.11; 100.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79 (0.67; 0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96 (0.92; 1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90 (0.84; 0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68 (0.51; 0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94 (0.83; 1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79 (0.67; 0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90 (0.78; 1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97 (0.92; 1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95 (0.90; 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.34 (3.88; 1204.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.80 (0.60; 231.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.83 (1.69; 492.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.61 (1.42; 498.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.32 (0.20; 138.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.33 (0.84; 278.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.27 (1.16; 548.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.27 (0.39; 175.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.30 (0.60; 213.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 (0.00; 0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04 (0.00; 0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10 (0.00; 0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32 (0.02; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.06 (0.00; 0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 (0.00; 0.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11 (0.00; 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03 (0.00; 0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05 (0.00; 0.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78 (0.74; 0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 (0.58; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54 (0.49; 0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 (0.54; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 (0.54; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47 (0.37; 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 (0.81; 0.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.57; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56 (0.50; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.43 (75.64; 80.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.83 (61.73; 63.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.57 (52.03; 55.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.29 (57.50; 70.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.29 (61.33; 67.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.37 (43.30; 51.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.78 (81.70; 85.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.42 (61.27; 63.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.69 (54.41; 56.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccuracy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.63 (72.60; 85.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.40 (56.20; 70.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.93 (49.35; 62.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.39 (54.58; 81.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.12 (49.07; 78.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.85 (41.03; 66.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.07 (76.00; 90.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.91 (54.69; 70.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.73 (48.94; 64.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYouden\u0026rsquo;s index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 (0.07; 0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04 (-0.02; 0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10 (0.02; 0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32 (0.19; 0.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.06 (-0.13; 0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 (-0.03; 0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10 (-0.03; 0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03 (-0.03; 0.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05 (-0.02; 0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77 (0.68; 0.86)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66 (0.58; 0.74)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70 (0.64; 0.77)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88 (0.77; 0.98)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78 (0.63; 0.93)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.74; 0.93)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68 (0.53; 0.83)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63 (0.54; 0.72)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 (0.56; 0.73)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eCUI values were classified as follows: excellent, \u0026ge;\u0026thinsp;0.81; good, \u0026ge;\u0026thinsp;0.64; fair, \u0026ge;\u0026thinsp;0.49; poor, \u0026le;\u0026thinsp;0.49; and very poor, \u0026le;\u0026thinsp;0.36 [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. An LR\u0026thinsp;+\u0026thinsp;value\u0026thinsp;\u0026ge;\u0026thinsp;10.0 indicates that a positive test almost confirmed the disease; a value of \u0026sim;6.0 indicates that the disease might be present; and a value of \u0026sim;1.0, indicating that the test was unable to determine the presence of the disease. An LR\u0026thinsp;+\u0026thinsp;value\u0026thinsp;\u0026le;\u0026thinsp;0.1 indicates that the disease was practically absent [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. Diagnostic odds ratio (DOR\u0026thinsp;=\u0026thinsp;LR+/LR-), the higher the DOR value the better the test [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. The Matthews correlation coefficient (MCC) is a value between \u0026minus;\u0026thinsp;1 and +\u0026thinsp;1; a value of +\u0026thinsp;1 represents a perfect prediction, 0 indicates no better than random prediction, and \u0026minus;\u0026thinsp;1 indicates total disagreement between prediction and observation [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003ePWH, people with HIV; PWoH, people without HIV; G1, Confirmed NS; G2, Presumptive NS; G3, Systemic syphilis; G4, PWH without SS and/or NS; G5, Negative control.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003ePositive and negative predictive values (PPV and NPV), positive and negative clinical utility index (CUI\u0026thinsp;+\u0026thinsp;and CUI\u0026minus;), positive and negative likelihood ratios (LR\u0026thinsp;+\u0026thinsp;and LR\u0026minus;), area under the ROC curve (AUC) (95% confidence interval), diagnostic odds ratio (DOR), Matthews correlation coefficient (MCC).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e(*) p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, p value indicated the difference between the AUC of the ROC curve and the baseline (random line).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical performance characteristics of CSF Total protein, as single test, with cutoff\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL or \u0026gt;\u0026thinsp;39 mg/dL, and combined CSF total protein\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL and/or CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u0026sup3;, as adjunct biomarkers to diagnose confirmed and presumptive neurosyphilis in PWH and PWoH.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePWH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003ePWoH\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1vs.G3\u0026thinsp;+\u0026thinsp;4\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2vs.G3\u0026thinsp;+\u0026thinsp;4\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u0026thinsp;+\u0026thinsp;2vs.G3\u0026thinsp;+\u0026thinsp;4\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1vs.G3\u0026thinsp;+\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2vs.G3\u0026thinsp;+\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u0026thinsp;+\u0026thinsp;2vs.G3\u0026thinsp;+\u0026thinsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1vs.G3\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2vs.G3\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u0026thinsp;+\u0026thinsp;2vs.G3\u0026thinsp;+\u0026thinsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eCSF total protein\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrue Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.43 (55.42; 84.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.35 (39.44; 63.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.62 (49.10; 67.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.27 (54.63; 92.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.50 (35.43; 84.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.05 (54.10; 84.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.00 (44.10; 85.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.28 (35.42; 61.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.56 (41.48; 63.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpecificity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.00 (83.18; 94.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.00 (83.18; 94.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.00 (83.18; 94.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.37 (49.82; 86.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.37 (49.82; 86.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.37 (49.82; 86.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.70 (91.58; 99.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.70 (91.58; 99.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.70 (91.58; 99.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.14 (4.04; 12.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.14 (2.87; 9.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.86 (3.35; 10.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.61 (1.40; 4.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.11 (1.05; 4.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.40 (1.30; 4.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.11 (5.50; 41.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.22 (4.15; 30.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.22 (4.58; 32.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32 (0.20; 0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54 (0.42; 0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46 (0.37; 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32 (0.14; 0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53 (0.27; 1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.24; 0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37 (0.20; 0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54 (0.42; 0.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.39; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.50 (9.18; 55.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.50 (4.48; 20.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.75 (6.32; 25.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.08 (2.21; 29.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.96 (1.07; 14.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.83 (1.97; 17.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.32 (10.61; 160.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.77 (6.73; 64.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.66 (8.24; 73.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51 (0.34; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.39 (0.24; 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.39; 0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53 (0.31; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35 (0.06; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 (0.37; 0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.24; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42 (0.26; 0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.34; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81 (0.76; 0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68 (0.62; 0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.57; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56 (0.41; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54 (0.39; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45 (0.30; 0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 (0.85; 0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72 (0.66; 0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68 (0.62; 0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.43 (58.58; 81.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.00 (63.92; 84.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.00 (76.43; 90.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.00 (53.24; 79.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.56 (38.44; 71.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.14 (64.58; 86.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.47 (56.31; 96.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.50 (76.04; 98.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91.11 (82.80; 99.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.00 (78.76; 90.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.00 (70.20; 79.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.23 (64.25; 73.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.17 (62.87; 89.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.00 (61.64; 86.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.33 (49.79; 75.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.71 (87.51; 97.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.79 (66.99; 82.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.63 (62.68; 78.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccuracy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.19 (78.76; 90.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.26 (68.57; 81.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.58 (68.52; 80.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.47 (58.92; 85.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.44 (51.46; 80.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.77 (58.17; 81.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.27 (83.25; 95.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.28 (34.95; 61.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.02 (68.91; 82.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYouden\u0026rsquo;s index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61 (0.39; 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.23; 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49 (0.32; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.04; 0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33 (-0.15; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.04; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (-0.64; -0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.27; -0.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.33; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 (0.83; 0.95)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82 (0.76; 0.88)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.79; 0.89)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79 (0.67; 0.92)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72 (0.57; 0.88)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76 (0.64; 0.88)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.91 (0.83; 0.98)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86 (0.76; 0.89)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 (0.79; 0.90)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eCSF total protein\u0026thinsp;\u0026gt;\u0026thinsp;39 mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrue Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.95 (65.88; 91.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.46 (47.41; 770.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.24 (57.91; 75.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.27 (54.63; 92.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.00 (47.62; 92.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.32 (59.76; 88.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.00 (62.11; 96.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.17 (41.54; 68.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.82 (51.13; 73.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpecificity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.83 (72.64; 87.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.83 (72.64; 87.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.83 (72.64; 87.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.67 (46.04; 83.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.67 (46.04; 83.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.67 (46.04; 83.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.95 (76.03; 91.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.95 (76.03; 91.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.95 (76.03; 91.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.22 (2.84; 6.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.10 (2.05; 4.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.51 (2.38; 5.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.32 (1.30; 4.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.25 (1.23; 4.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.29 (1.31; 4.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.65 (3.37; 9.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.67 (2.15; 6.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.17 (2.50; 6.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24 (0.13; 0.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.38; 0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.31; 0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34 (0.15; 0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38 (0.15; 0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36 (0.19; 0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.18 (0.06; 0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53 (0.39; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.32; 0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.92 (7.33; 43.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.19 (3.23; 11.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.66 (4.76; 15.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.80 (1.89; 24.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.00 (1.50; 23.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.44 (2.16; 19.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.98 (8.27; 123.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.94 (3.22; 14.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.53 (4.59; 19.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.33; 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.39 (0.25; 0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.42; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51 (0.28; 0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43 (0.16; 0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58 (0.42; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47 (0.25; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38 (0.22; 0.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49 (0.36; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75 (0.69; 0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.56; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58 (0.52; 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.37; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55 (0.39; 0.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.29; 0.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82 (0.77; 0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 (0.57; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.55; 0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.65 (49.88; 68.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.67 (55.87; 74.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.23 (69.69; 83.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.38 (51.41; 77.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.14 (42.16; 70.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.32 (64.75; 84.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.84 (42.01; 67.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.57 (57.23; 79.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.78 (67.71; 85.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.38 (86.60; 95.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.38 (70.77; 81.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.85 (65.98; 77.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.26 (61.43; 89.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.82 (64.90; 91.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.67 (51.58; 78.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.34 (90.24; 98.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.24 (69.28; 80.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.15 (66.85; 78.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccuracy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.86 (73.95; 86.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.68 (65.84; 78.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.15 (68.07; 79.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.43 (56.74; 83.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.77 (53.87; 82.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.31 (59.81; 82.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.96 (77.01; 90.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.51 (65.72; 80.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.85 (67.66; 81.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYouden\u0026rsquo;s index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61 (0.39; 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.23; 0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49 (0.32; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.04; 0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33 (-0.15; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.04; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61 (0.36; 0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.27; 0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.33; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89 (0.83; 0.95)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82 (0.76; 0.88)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84 (0.79; 0.89)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79 (0.67; 0.92)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72 (0.57; 0.88)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76 (0.64; 0.88)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.91 (0.83; 0.98)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86 (0.76; 0.89)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 (0.79; 0.90)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eCSF total protein\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL and/or WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u0026sup3;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrue Positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSensitivity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.81 (60.51; 87.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.41 (44.08; 66.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.07 (53.24; 70.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.82 (59.72; 94.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68.75 (41.34; 88.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.32 (59.76; 88.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65 (40.78; 84.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.72 (38.22; 65.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.13 (43.44; 66.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpecificity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.50 (81.58; 93.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.50 (81.58; 93.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.50 (81.58; 93.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.37 (49.82; 86.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.37 (49.82; 86.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.37 (49.82; 86.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.47 (85.10; 96.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.47 (85.10; 96.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.47 (85.10; 96.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.91 (3.56; 9.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.43 (2.65; 7.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.97 (3.03; 8.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.76 (1.49; 5.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.32 (1.19; 4.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.58 (1.40; 4.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.64 (3.95; 18.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.87 (3.23; 14.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.32 (3.49; 15.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLR (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30 (0.18; 0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51 (0.39; 0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43 (0.34; 0.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.26 (0.10; 0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.21; 0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34 (0.18; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38 (0.21; 0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.40; 0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49 (0.38; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.78 (8.22; 47.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.70 (4.28; 17.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.46 (5.93; 22.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.50 (0.87; 23.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.75 (0.51; 14.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.65 (2.51; 23.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.82 (6.88; 75.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.16 (5.21; 33.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.09 (6.20; 36.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.33; 0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41 (0.26; 0.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51 (0.41; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57 (0.36; 0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40 (0.12; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (0.43; 0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42 (0.17; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42 (0.26; 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.17 (0.00; 0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCUI-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79 (0.74; 0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67 (0.61; 0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.56; 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58 (0.44; 0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56 (0.41; 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.33; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86 (0.81; 0.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70 (0.64; 0.757)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59 (0.51; 0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.39 (53.84; 80.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.21 (61.62; 84.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.76 (74.82; 90.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.23 (54.91; 80.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.89 (41.33; 72.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.38 (66.38; 86.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.00 (45.94; 80.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.08 (66.84; 90.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.00 (74.56; 92.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPV, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.52 (85.19; 95.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.09 (68.97; 83.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.47 (63.14; 77.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.61 (65.44; 92.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79.17 (63.83; 89.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.86 (53.15; 79.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.47 (87.08; 95.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.44 (70.05; 80.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.07 (65.62; 75.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAccuracy, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.95 (77.37; 89.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.26 (68.57; 81.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.00 (68.97; 80.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.51 (61.13; 86.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.77 (53.87; 82.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73.85 (61.46; 83.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.61 (80.09; 93.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.82 (69.27; 83.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.44 (68.28; 81.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYouden\u0026rsquo;s index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61 (0.42; 0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43 (0.26; 0.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50 (0.41; 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.39 (-0.09; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47 (0.10; 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57 (0.26; 0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.23; 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.29; 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81 (0.72; 0.89)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71 (0.64; 0.79)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75 (0.68; 0.81)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86 (0.76; 0.97)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76 (0.60; 0.91)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82 (0.73; 0.91)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67 (0.52; 0.83)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (0.48; 0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62 (0.50; 0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eCUI values were classified as follows: excellent, \u0026ge;\u0026thinsp;0.81; good, \u0026ge;\u0026thinsp;0.64; fair, \u0026ge;\u0026thinsp;0.49; poor, \u0026le;\u0026thinsp;0.49; and very poor, \u0026le;\u0026thinsp;0.36 [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. An LR\u0026thinsp;+\u0026thinsp;value\u0026thinsp;\u0026ge;\u0026thinsp;10.0 indicates that a positive test almost confirmed the disease; a value of \u0026sim;6.0 indicates that the disease might be present; and a value of \u0026sim;1.0, indicating that the test was unable to determine the presence of the disease. An LR\u0026thinsp;+\u0026thinsp;value\u0026thinsp;\u0026le;\u0026thinsp;0.1 indicates that the disease was practically absent [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. Diagnostic odds ratio (DOR\u0026thinsp;=\u0026thinsp;LR+/LR-), the higher the DOR value the better the test [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. The Matthews correlation coefficient (MCC) is a value between \u0026minus;\u0026thinsp;1 and +\u0026thinsp;1; a value of +\u0026thinsp;1 represents a perfect prediction, 0 indicates no better than random prediction, and \u0026minus;\u0026thinsp;1 indicates total disagreement between prediction and observation [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003ePWH, people with HIV; PWoH, people without HIV; G1, Confirmed NS; G2, Presumptive NS; G3, Systemic syphilis; G4, PWH without SS and/or NS; G5, Negative control.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003ePositive and negative predictive values (PPV and NPV), positive and negative clinical utility index (CUI\u0026thinsp;+\u0026thinsp;and CUI\u0026minus;), positive and negative likelihood ratios (LR\u0026thinsp;+\u0026thinsp;and LR\u0026minus;), area under the ROC curve (AUC) (95% confidence interval), diagnostic odds ratio (DOR), Matthews correlation coefficient (MCC).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003e(*) p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, p value indicated the difference between the AUC of the ROC curve and the baseline (random line).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cp\u003eOverall, the DCPC of CSF TP, as a single test, was higher in PWoH than in PWH, despite the cutoff point applied. AUC and MCC were higher in PWoH than in PWH (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe best cutoff point calculated for CSF TP was \u0026gt;\u0026thinsp;39 mg/dL; for CSF TP, this cutoff sensitivity and NPV were higher than the cutoff point of \u0026gt;\u0026thinsp;45 mg/dL, but with lower specificity in all groups analyzed. LR\u0026thinsp;+\u0026thinsp;and LR- were higher with a cutoff point of 45 mg/dL, indicating that the chance of a positive test confirming the disease was more significant with this cutoff (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe post-test diagnostic probability for a positive and negative test of CSF TP or CSF WBC single tests to diagnose confirmed NS in PWH and/or PWoH is shown in Figs.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Supplementary Fig.\u0026nbsp;1.\u003c/p\u003e\n \u003cp\u003eThe DCPC of the association of CSF TP (\u0026gt;\u0026thinsp;45 mg/dL) and/or WBC count (\u0026gt;\u0026thinsp;5 cells/mm\u0026sup3;) as adjunct biomarkers to diagnose confirmed or presumptive NS in PWH or PWoH is shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4 CSF Lactate\u003c/h2\u003e\n \u003cp\u003eAmong PWH and PWoH, CSF LA levels were within the reference ranges and comparable between the NS and SS groups (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). For PWH the AUC of CSF LA (mmol/L) to diagnose confirmed and presumptive NS (G1 and G2) was 0.69 (0.53, 0.85; p\u0026thinsp;=\u0026thinsp;0.025), whereas that for PWoH was 0.54 (0.45, 0.64; p\u0026thinsp;=\u0026thinsp;0.387). Overall, the participants the AUC was 0.58 (0.49, 0.66; p\u0026thinsp;=\u0026thinsp;0.069).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eIn contrast to most published studies that analyzed these groups together [Dumaresq et al. 2013; Ghanem et al. 2008; Lee et al. 2015; Dunaway et al. 2020; Cai et al. 2017; He et al. 2021; Li et al. 2019; Lin et al. 2014; Pastuszczak et al. 2013], we analyzed CSF biomarkers in symptomatic confirmed and presumptive NS separately. Analysis of the DCPC of these CSF biomarkers in presumptive NS is particularly important, as CSF nontreponemal antibody assays are negative [Wharton et al. 1990].\u003c/p\u003e \u003cp\u003eIn our study, elevation of CSF WBC and TP was more frequent in PWH than in PWoH. In PWH among confirmed than in presumptive NS. In confirmed NS, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u003csup\u003e3\u003c/sup\u003e and CSF protein\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL was observed in 30% and 74%, respectively, whereas in presumptive NS, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u003csup\u003e3\u003c/sup\u003e and CSF protein\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL was observed in 28% and 91%, respectively; both were significantly different [Jiang et al. 2018].\u003c/p\u003e \u003cp\u003eIn PWH, symptomatic NS patients showed more CSF abnormalities on the initial LP than asymptomatic patients; CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;10 cells/ mm\u003csup\u003e3\u003c/sup\u003e was observed in 70% of symptomatic NS and 46% of the asymptomatic NS. CSF protein\u0026thinsp;\u0026gt;\u0026thinsp;50 mg/dL was present in 61% of symptomatic NS, and 58% of the asymptomatic [Ghanem et al. 2008]. In PWH with early syphilis, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;20 cells/mm\u003csup\u003e3\u003c/sup\u003e was observed in 37% [Dumaresq et al. 2013]. PWH with ocular syphilis CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u003csup\u003e3\u003c/sup\u003e was observed in 37.50%, and CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;40 mg/dL in 56% [Lee et al. 2015].\u003c/p\u003e \u003cp\u003eBetween PWH and PWoH with confirmed and presumptive NS altogether, including 44% with symptomatic NS, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;20 cells/mm\u003csup\u003e3\u003c/sup\u003e was observed in 63% and CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;50 mg/dL in 61% [Dunaway et al. 2020]. However, among asymptomatic NS in PWoH, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u003csup\u003e3\u003c/sup\u003e was observed in 83%, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;20 cells/mm\u003csup\u003e3\u003c/sup\u003e in 5%, CSF protein\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL was observed in 20% [Cai et al. 2017].\u003c/p\u003e \u003cp\u003eA previous study reported PWoH CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/ mm\u003csup\u003e3\u003c/sup\u003e in ~\u0026thinsp;81% of symptomatic and asymptomatic NS [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Increased CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 or 50 mg/dL was observed in 68\u0026ndash;78% of symptomatic NS, but less frequently in asymptomatic NS, between 29\u0026ndash;51% [He et al. 2021; Li et al. 2019]. In PWoH with symptomatic NS and psychiatric manifestations, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;10 cells/ mm\u003csup\u003e3\u003c/sup\u003e was observed in 54%, CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;50 mg/dL in 60%, and both CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;50 mg/dL and CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;10 cells/mm\u003csup\u003e3\u003c/sup\u003e in 44% [Lin et al. 2014]. In PWoH with secondary and early latent syphilis and a serum VDRL\u0026thinsp;\u0026ge;\u0026thinsp;1:32, symptomatic and asymptomatic NS, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u003csup\u003e3\u003c/sup\u003e was observed in 42%, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;10 cells/mm\u003csup\u003e3\u003c/sup\u003e in 30%, and CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;20 cells/ mm\u003csup\u003e3\u003c/sup\u003e in 18%. CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL in 39%, CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL, and CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u003csup\u003e3\u003c/sup\u003e in 30% [Pastuszczak et al. 2013].\u003c/p\u003e \u003cp\u003eThe prevalence of abnormal CSF protein concentrations varies depending on the clinical form of neurosyphilis [Simon 1985].\u003c/p\u003e \u003cp\u003eIn this study for the DCPC of CSF TP with cutoff\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL, the sensitivity is low for diagnosis of confirmed NS in PWoH, meaning a positive test does not often occur in those with the condition, and the specificity is high, meaning a negative test often occurs in those without confirmed NS. The PPV of the test is low, false positives are common in those who screen positive, possibly limiting confirmation. The NPV of the test is high, indicating that false negatives are uncommon in those who screen negative. The clinical utility of the test is very poor for confirmation but excellent for screening. The value of the CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL single test for both screening and confirmation is good, but depends on prevalence. However, in PWH, the value of the CSF TP with a cutoff\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL for both screening and confirmation, NS is fair and subject to prevalence.\u003c/p\u003e \u003cp\u003eConcerning the diagnosis of presumptive NS in PWoH, the DCPC of CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL were lower than that for the diagnosis of confirmed NS. The sensitivity of the test was very low, but its specificity was high. The PPV and NPV of the test are modest, meaning that false positives or negatives are common. The clinical utility of the test is very poor for confirmation but good for screening. The value of CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL for both screening and confirmation is fair and subject to prevalence. However, in PWH, the sensitivity of CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL is very low, indicating that a positive test rarely occurs in those with presumptive NS. The specificity of the test is low, meaning that a negative test result does not often occur in those without the condition. The PPV and NPV of the test is very low, the value of CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL to diagnose presumptive NS in PWH for both screening and case finding is poor.\u003c/p\u003e \u003cp\u003eIn our study, in PWoH, the DCPC of CSF WBC to diagnose confirmed NS, with a cutoff CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;20 cells/mm\u003csup\u003e3\u003c/sup\u003e, has extremely low sensitivity and very high specificity. The PPV of the test is almost perfect, meaning that false positives are rare in those who screen positive, suggesting a potentially useful confirmatory test. The NPV of the test is modest, meaning that occasional false negatives occur among those who screen negative. The clinical utility of the test is very poor for case finding, but good for screening. However, in the PWH group, the DCPC of CSF WBC with a cutoff\u0026thinsp;\u0026gt;\u0026thinsp;5 cells/mm\u003csup\u003e3\u003c/sup\u003e, the sensitivity of the test is very low and the specificity is high for diagnosing confirmed NS. The PPV of the test is modest, meaning that false positives are a little more common in those who screen positive. The NPV of the test is low, indicating that false negatives are common in those who screen negative, possibly limiting screening applications. The clinical utility of the test is very poor for confirmation, and fair for screening. The value of this single test for both screening and confirmation is fair and subject to prevalence. However, in the PWH group for CSF WBC with a cutoff\u0026thinsp;\u0026gt;\u0026thinsp;10 or 20 cells/mm\u003csup\u003e3\u003c/sup\u003e, the specificity of the test is very high, meaning a negative test often occurs in those without the condition, which is in accordance with a previous report [Marra et al. 1996; Marra 2007]. The PPV of the test is almost perfect, meaning that false positives are rare in those who screen positive, offering a candidate confirmatory test. The value of CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;10 or 20 cells/mm\u003csup\u003e3\u003c/sup\u003e was considered moderate for screening.\u003c/p\u003e \u003cp\u003eIn the PWH for WBC count, with the cutoffs\u0026thinsp;\u0026gt;\u0026thinsp;10 or \u0026gt;\u0026thinsp;20 cells/mm\u003csup\u003e3\u003c/sup\u003e, the PPV is almost perfect for the diagnosis of presumptive NS, meaning false positives are very rare in those who screen positive, suggesting a candidate confirmatory test. These cutoff values are moderate for screening. However, in the PWoH group, WBC count for the diagnosis of presumptive NS showed the worst DCPC. The best characteristic for CSF WBC count\u0026thinsp;\u0026gt;\u0026thinsp;20 cells/mm\u003csup\u003e3\u003c/sup\u003e was the specificity of the test, which was very high. The PPV of the test was almost perfect, suggesting that it represents a potentially useful confirmatory test. The clinical utility of the screening test was fair.\u003c/p\u003e \u003cp\u003eCSF pleocytosis in syphilis is lymphocyte predominant. Polymorphonuclear lymphocytes may predominate, particularly in cases of acute syphilitic meningitis [Ghanem 2010]. A cutoff of \u0026ge;\u0026thinsp;5 cells/mL has been the standard; this has less specificity among PWH owing to nonspecific abnormalities associated with the HIV infection itself [Marra et al. 1996; Spudich et al. 2005]. Our findings support previous studies on PWH-confirmed and presumptive NS. Because HIV can cause mild mononuclear CSF pleocytosis, 15.6% of CSF samples from PWH had\u0026thinsp;\u0026gt;\u0026thinsp;10 cells/mm\u003csup\u003e3\u003c/sup\u003e with progressive decline in CSF WBC count with advancing stages of AIDS [Marshall et al. 1988]. Limited data suggest a cutoff of 10 cells/mL for PWH when the peripheral blood CD4 T cell concentration is low or patients are on antiretrovirals, because these lower the risk of HIV-related pleocytosis [Ghanem et al. 2008], and 20 cells/mL for those not on antiretroviral therapy may improve the specificity for diagnosing neurosyphilis [Marra et al. 2007].\u003c/p\u003e \u003cp\u003eIn this study the combination of CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;45 mg/dL and/or WBC\u0026thinsp;\u0026gt;\u0026thinsp;5.0 cells/mm\u003csup\u003e3\u003c/sup\u003e, in PWoH for the diagnosis of confirmed NS, the value for both screening and confirmation is good, but depends on the prevalence. This combination was excellent for screening. However, in PWoH for diagnosis of presumptive NS, this combination is suitable for screening, and its best feature is its specificity. In PWH, the same combination for the diagnosis of confirmed or presumptive had low sensitivity. The PPV and NPV of the combination were both low, possibly limiting confirmation and screening applications. The clinical utility of the test for confirmation and screening are very poor and is therefore not recommended for either application.\u003c/p\u003e \u003cp\u003eMost studies investigating the DCPC of CSF TP and WBC were performed in PWoH, with few in PWH. Furthermore, few have previously investigated DCPC separately on confirmed and presumptive NS. A study in PWoH, analyzing separately confirmed and presumptive NS, as in our study, the sensitivity and specificity of CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;10 cells/mm\u0026sup3; were 65.38% and 75.26% for diagnosing confirmed NS and 64.71% and 76.81% for presumptive NS, respectively. For CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;50 mg/dL, the sensitivity was 53.85% and 55.56% for confirmed and presumptive NS, respectively, and specificity was 86.05% and 68.12%, respectively [Lin et al. 2016].\u003c/p\u003e \u003cp\u003eIn other studies, in PWoH, to diagnose confirmed and presumptive NS together, sensitivities and specificities for CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;3 cells/mm\u0026sup3; were 48.00% and 82.00%, respectively; for CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;49.7 mg/dL, they were 54.00% and 85.71%, respectively; for the association of CSF TP\u0026thinsp;\u0026gt;\u0026thinsp;49.7 mg/dL, CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;3 cells/mm\u0026sup3;, and neurological symptoms were 92.50% and 33.30%, respectively [Tong et al. 2013]. The sensitivity and specificity of CSF WBC\u0026thinsp;\u0026gt;\u0026thinsp;10 cells/mm\u0026sup3; to diagnose confirmed NS and presumptive NS together were 59.50% and 92.50%, respectively [Liu et al. 2013].\u003c/p\u003e \u003cp\u003eA lower cutoff point for PWH CSF TP, such as 39 mg/dL, proved advantageous, especially for increasing diagnostic sensitivity. These findings reinforce previous guidelines, which recommended CSF TP cutoff point\u0026thinsp;\u0026gt;\u0026thinsp;40 mg/dL [Workowski and Bolan 2015; Klein et al. 2020].\u003c/p\u003e \u003cp\u003eCSF LA do not add to the diagnose of NS, however among PWH and PWoH, CSF LA is suitable for discriminating between other causes of chronic meningitis with an increase in CSF LA, such as tuberculous meningitis or \u003cem\u003eCryptococcus sp\u003c/em\u003e [de Almeida et al. 2022].\u003c/p\u003e \u003cp\u003eThe results of this study were limited mainly by its retrospective nature; some analyses were limited by the small sample sizes.\u003c/p\u003e \u003cp\u003eCSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, which were better in the former. HIV co-infection greatly affects the DCPC of these biomarkers for the diagnosis of NS. The development of novel NS diagnostics is of paramount importance, particularly in settings where non-treponemal tests are negative with high clinical suspicion [Boog et al. 2021; Marks et al. 2018; Ramachandran and Wilson 2020].\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. The protocols were approved by the Institutional Review Board of the Hospital de Cl\u0026iacute;nicas, Universidade Federal do Paran\u0026aacute; (Curitiba, Paran\u0026aacute;, Brazil). Written informed consent was waived by the local IRB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no competing interests to declare regarding the publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProf. Sergio Monteiro de Almeida, declare that he has full access to all of the data.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAnonymized data from the current study will be made available at the request of qualified investigators if approved by our Research Ethics Board.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.M.A. participated in the conception and design of the work, revised the manuscript critically for important intellectual content; S.M.A. and J.T.N. participated in the acquisition, analysis, and interpretation of data; prepared all figures and tables; A.M.R, A.C.M., and D.Z.G participated in the data acquisition; F.G. participated in the design of the work; data analysis and revised it critically. All authors approved the version to be published; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGuarner J, Jost H, Pillay A, Sun Y, Cox D, Notenboom R, Workowski K (2015) Evaluation of Treponemal Serum Tests Performed on Cerebrospinal Fluid for Diagnosis of Neurosyphilis. Am J Clin Pathol 143(4):479\u0026ndash;484. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1309/AJCPWSL3G8RXMCQR\u003c/span\u003e\u003cspan address=\"10.1309/AJCPWSL3G8RXMCQR\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu J, Shi JC, Wan H, Li J, Shao Y, Ye J, Dai L, Wang X, Liu A (2021) Clinical characteristics, diagnosis, and predictors of neurosyphilis patients with human immunodeficiency virus co-infection: A retrospective study at infectious diseases hospitals in two cities of China. Medicine 100(42):e27430. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/MD.0000000000027430\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000027430\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDumaresq J, Langevin S, Gagnon S, Serhir B, Deligne B, Tremblay C, Tsang RSW, Fortin C, Coutlee F, Roger M (2013) Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis. J Clin Microbiol 51(12):4060. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1128/JCM.01989-13\u003c/span\u003e\u003cspan address=\"10.1128/JCM.01989-13\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalamano R, Ballest\u0026eacute; R, Perna A, Rodriguez N, Lombardo D, Garc\u0026iacute;a N, L\u0026oacute;pez P, Cappuccio P (2016) Cerebrospinal fluid examination may be useful in diagnosing neurosyphilis in asymptomatic HIV\u0026thinsp;+\u0026thinsp;patients with syphilis. Arq Neuropsiquiatr 74(2):128\u0026ndash;132. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1590/0004-282X20160016\u003c/span\u003e\u003cspan address=\"10.1590/0004-282X20160016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeraru ER, Aronow HA, Lipton RB (1990) Neurosyphilis in AIDS patients: initial CSF VDRL may be negative. Neurology 40(3 Pt 1):541\u0026ndash;543. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1212/WNL.40.3_PART_1.541\u003c/span\u003e\u003cspan address=\"10.1212/WNL.40.3_PART_1.541\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrasil, Minist\u0026eacute;rio da Sa\u0026uacute;de (2018) Protocolo Cl\u0026iacute;nico e Diretrizes Terap\u0026ecirc;uticas para Manejo da Infec\u0026ccedil;\u0026atilde;o pelo HIV em Adultos / Minist\u0026eacute;rio da Sa\u0026uacute;de, Secretaria de Vigil\u0026acirc;ncia em Sa\u0026uacute;de, Departamento de Vigil\u0026acirc;ncia, Preven\u0026ccedil;\u0026atilde;o e Controle das Infec\u0026ccedil;\u0026otilde;es Sexualmente Transmiss\u0026iacute;veis. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.aids.gov.br/assistencia/manualdst/item12.html\u003c/span\u003e\u003cspan address=\"http://www.aids.gov.br/assistencia/manualdst/item12.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrasil, Minist\u0026eacute;rio da Sa\u0026uacute;de (2011) Fluxograma Laboratorial da S\u0026iacute;filis e a utiliza\u0026ccedil;\u0026atilde;o de testes r\u0026aacute;pidos para triagem da s\u0026iacute;filis em situa\u0026ccedil;\u0026otilde;es especiais e apresenta outras recomenda\u0026ccedil;\u0026otilde;es. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://bvsms.saude.gov.br/bvs/saudelegis/gm/2011/prt3242_30_12_2011.html\u003c/span\u003e\u003cspan address=\"https://bvsms.saude.gov.br/bvs/saudelegis/gm/2011/prt3242_30_12_2011.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrasil, Minist\u0026eacute;rio da Sa\u0026uacute;de (2022) Protocolo cl\u0026iacute;nico e diretrizes terap\u0026ecirc;uticas para aten\u0026ccedil;\u0026atilde;o integral \u0026agrave;s pessoas com infec\u0026ccedil;\u0026otilde;es sexualmente transmiss\u0026iacute;veis (IST). Secret\u0026aacute;ria Vigil\u0026acirc;ncia em Sa\u0026uacute;de. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://bvsms.saude.gov.br/bvs/publicacoes/protocolo_clinico_atecao_integral_ist.pdf\u003c/span\u003e\u003cspan address=\"http://bvsms.saude.gov.br/bvs/publicacoes/protocolo_clinico_atecao_integral_ist.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWharton M, Chorba TL, Vogt RL, Morse DL, Buehler JW (1990) Case definitions for public health surveillance. MMWR Recomm Rep 39(RR\u0026ndash;13):1\u0026ndash;43 PMID: 2122225\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrench P, Gomberg M, Janier M, Schmidt BL, van Voorst Vader PC, Young H (2009) IUSTI: 2008 European Guidelines on the Management of Syphilis. Int J STD AIDS 20(5):300\u0026ndash;309. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1258/IJSA.2008.008510\u003c/span\u003e\u003cspan address=\"10.1258/IJSA.2008.008510\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorkowski KA, Bolan GA (2015) Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report. Recommendations and Reports, 64(RR-03), 1. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/00019048-200206000-00012\u003c/span\u003e\u003cspan address=\"10.1097/00019048-200206000-00012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIzzat NN, Bartruff JK, Glicksman JM, Holder WR, Knox JM (1971) Validity of the VDRL test on cerebrospinal fluid contaminated by blood. Br J Vener Dis 47(3):162. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/STI.47.3.162\u003c/span\u003e\u003cspan address=\"10.1136/STI.47.3.162\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRotta O (2005) Serological diagnosis of syphilis * Diagn\u0026oacute;stico sorol\u0026oacute;gico da s\u0026iacute;filis *. An Bras Dermatol 80(3):299\u0026ndash;302\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarra CM (2015) Neurosyphilis. In CONTINUUM Lifelong Learning in Neurology (Vol.\u0026nbsp;21, Issue 6). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1212/CON.0000000000000250\u003c/span\u003e\u003cspan address=\"10.1212/CON.0000000000000250\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu L, Gu X, Peng RR, Wang C, Gao Z, Zhou P, Gao Y, Shi M, Guan Z, Se\u0026ntilde;ac AC (2014) Comparison of the cerebrospinal fluid (CSF) toluidine red unheated serum test and the CSF rapid plasma reagin test with the CSF Venereal Disease Research Laboratory test for diagnosis of neurosyphilis among HIV-negative syphilis patients in China. J Clin Microbiol 52(3):736\u0026ndash;740. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1128/JCM.02522-13/SUPPL_FILE/ZJM999093171SO1.PDF\u003c/span\u003e\u003cspan address=\"10.1128/JCM.02522-13/SUPPL_FILE/ZJM999093171SO1.PDF\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoog GHP, Lopes JVZ, Mahler JV, Solti M, Kawahara LT, Teng AK, Munhoz JVT, Levin AS (2021) Diagnostic tools for neurosyphilis: a systematic review. BMC Infect Dis 21(1):1\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/S12879-021-06264-8/FIGURES/4\u003c/span\u003e\u003cspan address=\"10.1186/S12879-021-06264-8/FIGURES/4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonzalez H, Koralnik IJ, Marra CM (2019) Neurosyphilis Seminars in Neurology 39(04):448\u0026ndash;455. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1055/S-0039-1688942\u003c/span\u003e\u003cspan address=\"10.1055/S-0039-1688942\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRopper AH (2019) Neurosyphilis. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003eHttps://Doi.Org/10.1056/NEJMra1906228\u003c/span\u003e\u003cspan address=\"Https://Doi.Org/10.1056/NEJMra1906228\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, 381(14), 1358\u0026ndash;1363. https://doi.org/10.1056/NEJMRA1906228\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarsen SA, Steiner BM, Rudolph AH (1995) Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 8(1):1. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1128/CMR.8.1.1\u003c/span\u003e\u003cspan address=\"10.1128/CMR.8.1.1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Almeida SM, Barros N, Fernandes Dos Santos A, Custodio G, Petterle RR, Nogueira K, Nogueira MB (2020) Clinical performance of amperometry compared with enzymatic ultra violet method for lactate quantification in cerebrospinal fluid. Diagnosis (Berlin Germany) 8(4):510\u0026ndash;514. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1515/DX-2020-0065\u003c/span\u003e\u003cspan address=\"10.1515/DX-2020-0065\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeisenhammer F, Bartos A, Egg R, Gilhus NE, Giovannoni G, Rauer S, Sellebjerg F (2006) Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol 13(9):913\u0026ndash;922. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/J.1468-1331.2006.01493.X\u003c/span\u003e\u003cspan address=\"10.1111/J.1468-1331.2006.01493.X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitchell AJ (2008) The clinical significance of subjective memory complaints in the diagnosis of mild cognitive impairment and dementia: a meta-analysis. Int J Geriatr Psychiatry 23(11):1191\u0026ndash;1202. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/GPS.2053\u003c/span\u003e\u003cspan address=\"10.1002/GPS.2053\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitchell AJ (2011) Sensitivity \u0026times; PPV is a recognized test called the clinical utility index (CUI+). Eur J Epidemiol 2011 26(3):251\u0026ndash;252. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/S10654-011-9561-X\u003c/span\u003e\u003cspan address=\"10.1007/S10654-011-9561-X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkobeng AK (2007a) Understanding diagnostic tests 2: likelihood ratios, pre- and post-test probabilities and their use in clinical practice. Acta Paediatrica (Oslo, Norway: 1992), 96(4), 487\u0026ndash;491. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/J.1651-2227.2006.00179.X\u003c/span\u003e\u003cspan address=\"10.1111/J.1651-2227.2006.00179.X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PMM (2003) The diagnostic odds ratio: A single indicator of test performance. J Clin Epidemiol 56(11):1129\u0026ndash;1135. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0895-4356(03)00177-X\u003c/span\u003e\u003cspan address=\"10.1016/S0895-4356(03)00177-X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGee S (2002) Simplifying Likelihood Ratios. J Gen Intern Med 17(8):647. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1046/J.1525-1497.2002.10750.X\u003c/span\u003e\u003cspan address=\"10.1046/J.1525-1497.2002.10750.X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatthews BW (1975) Comparison of the predicted and observed secondary structure of T4 phage lysozyme. Biochim Biophys Acta 405(2):442\u0026ndash;451. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0005-2795(75)90109-9\u003c/span\u003e\u003cspan address=\"10.1016/0005-2795(75)90109-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSackett DL, Haynes RB (2002) Evidence base of clinical diagnosis: The architecture of diagnostic research. BMJ: Br Med J 324(7336):539. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/BMJ.324.7336.539\u003c/span\u003e\u003cspan address=\"10.1136/BMJ.324.7336.539\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTJ F (1975) Letter: Nomogram for Bayes theorem. N Engl J Med 293(5):257\u0026ndash;257. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJM197507312930513\u003c/span\u003e\u003cspan address=\"10.1056/NEJM197507312930513\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkobeng AK (2007b) Understanding diagnostic tests 3: Receiver operating characteristic curves. Acta Paediatrica (Oslo, Norway: 1992), 96(5), 644\u0026ndash;647. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/J.1651-2227.2006.00178.X\u003c/span\u003e\u003cspan address=\"10.1111/J.1651-2227.2006.00178.X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Almeida SM, Bhatt A, Riggs PK, Durelle J, Lazzaretto D, Marquie-Beck J, McCutchan A, Letendre S, Ellis R (2010) Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis. J Neurovirol 16(1):6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3109/13550280903514776\u003c/span\u003e\u003cspan address=\"10.3109/13550280903514776\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan L, Yu A, Zhang D, Wang Z, Ma P (2021) Consequences of HIV/Syphilis Co-Infection on HIV Viral Load and Immune Response to Antiretroviral Therapy. Infect Drug Resist 14:2851. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/IDR.S320648\u003c/span\u003e\u003cspan address=\"10.2147/IDR.S320648\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalacios R, Jim\u0026eacute;nez-O\u0026ntilde;ate F, Aguilar M, Galindo MJ, Rivas P, Ocampo A, Berenguer J, Arranz JA, R\u0026iacute;os MJ, Knobel H, Moreno F, Ena J, Santos J (2007) Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes (1999), 44(3), 356\u0026ndash;359. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/QAI.0B013E31802EA4C6\u003c/span\u003e\u003cspan address=\"10.1097/QAI.0B013E31802EA4C6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA, London AIDS (2008) England), 22(10), 1145. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/QAD.0B013E32830184DF\u003c/span\u003e\u003cspan address=\"10.1097/QAD.0B013E32830184DF\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee SY, Cheng V, Rodger D, Rao N (2015) Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection. J Ophthalmic Inflamm Infect 5(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/S12348-015-0056-X\u003c/span\u003e\u003cspan address=\"10.1186/S12348-015-0056-X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDunaway SB, Maxwell CL, Tantalo LC, Sahi SK, Marra CM (2020) Neurosyphilis Treatment Outcomes After Intravenous Penicillin G Versus Intramuscular Procaine Penicillin Plus Oral Probenecid. 71(2):267. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/CID/CIZ795\u003c/span\u003e\u003cspan address=\"10.1093/CID/CIZ795\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCai SN, Long J, Chen C, Wan G, Lun WH (2017) Incidence of asymptomatic neurosyphilis in serofast Chinese syphilis patients. Sci Rep 7(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/S41598-017-15641-W\u003c/span\u003e\u003cspan address=\"10.1038/S41598-017-15641-W\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe C, Kong Q, Shang X, Duan Y, Cui Y, Wang J, Ci C, Sang H (2021) Clinical, laboratory and brain Magnetic Resonance Imaging (MRI) characteristics of asymptomatic and symptomatic HIV-negative neurosyphilis patients. J Infect Chemotherapy: Official J Japan Soc Chemother 27(11):1596\u0026ndash;1601. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/J.JIAC.2021.07.004\u003c/span\u003e\u003cspan address=\"10.1016/J.JIAC.2021.07.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi W, Jiang M, Xu D, Kou C, Zhang L, Gao J, Qin K, Wu W, Zhang X (2019) Clinical and Laboratory Characteristics of Symptomatic and Asymptomatic Neurosyphilis in HIV-Negative Patients: A Retrospective Study of 264 Cases. BioMed Research International, 2019. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2019/2426313\u003c/span\u003e\u003cspan address=\"10.1155/2019/2426313\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin LR, Zhang HL, Huang SJ, Zeng YL, Xi Y, Guo XJ, Liu GL, Tong ML, Zheng WH, Liu LL, Yang TC (2014) Psychiatric manifestations as primary symptom of neurosyphilis among HIV-negative patients. J Neuropsychiatry Clin Neurosci 26(3):233\u0026ndash;240. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1176/APPI.NEUROPSYCH.13030064\u003c/span\u003e\u003cspan address=\"10.1176/APPI.NEUROPSYCH.13030064\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePastuszczak M, Zeman J, Jaworek AK, Wojas-Pelc A (2013) Cerebrospinal Fluid Abnormalities in HIV-Negative Patients with Secondary and Early Latent Syphilis and Serum VDRL\u0026thinsp;\u0026ge;\u0026thinsp;1:32. Indian J Dermatology 58(4):325. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.4103/0019-5154.113941\u003c/span\u003e\u003cspan address=\"10.4103/0019-5154.113941\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimon RP (1985) Neurosyphilis. Arch Neurol 42(6):606\u0026ndash;613. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/ARCHNEUR.1985.04060060112021\u003c/span\u003e\u003cspan address=\"10.1001/ARCHNEUR.1985.04060060112021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarra CM, Gary DW, Kuypers J, Jacobson MA (1996) Diagnosis of Neurosyphilis in Patients Infected with Human Immunodeficiency Virus Type 1. J Infect Dis 174(1):219\u0026ndash;221. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/INFDIS/174.1.219\u003c/span\u003e\u003cspan address=\"10.1093/INFDIS/174.1.219\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarra CM (2007) D\u0026eacute;j\u0026agrave; Vu all over again: When to perform a lumbar puncture in HIV-infected patients with syphilis. Sex Transm Dis 34(3):145\u0026ndash;146. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/01.OLQ.0000251204.18648.15\u003c/span\u003e\u003cspan address=\"10.1097/01.OLQ.0000251204.18648.15\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhanem KG (2010) REVIEW: Neurosyphilis: A Historical Perspective and Review. CNS Neurosci Ther 16(5):e157. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/J.1755-5949.2010.00183.X\u003c/span\u003e\u003cspan address=\"10.1111/J.1755-5949.2010.00183.X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpudich SS, Nilsson AC, Lollo ND, Liegler TJ, Petropoulos CJ, Deeks SG, Paxinos EE, Price RW (2005) Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC Infect Dis. 5\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1471-2334-5-98\u003c/span\u003e\u003cspan address=\"10.1186/1471-2334-5-98\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin L-R, Lin D-H, Tong M-L, Liu L-L, Fan J-Y, Zhu X-Z, Gao K, Chen M-J, Zheng W-H, Zhang H-L, Li S-L, Lin H-L, Lin Z-F, Niu J-J, Yang T-C (2016) Macrophage migration inhibitory factor as a novel cerebrospinal fluid marker for neurosyphilis among HIV-negative patients. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.cca.2016.10.018\u003c/span\u003e\u003cspan address=\"10.1016/j.cca.2016.10.018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTong ML, Liu LL, Zeng YL, Zhang HL, Liu GL, Zheng WH, Dong J, Wu JY, Su YH, Lin LR, Yang TC (2013) Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom. Diagn Microbiol Infect Dis 75(4):377\u0026ndash;380. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/J.DIAGMICROBIO.2013.01.013\u003c/span\u003e\u003cspan address=\"10.1016/J.DIAGMICROBIO.2013.01.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu LL, Zhang HL, Huang SJ, Liu L, Tong ML, Lin LR, Chen YY, Xi Y, Guo XJ, Zhang YF, Zhang Q, Zheng WH, Chen FY, Jiang J, Yang TC (2013) Assessing cerebrospinal fluid abnormalities in neurosyphilis patients without human immunodeficiency virus infection. Int Immunopharmacol 17(4):1120\u0026ndash;1124. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/J.INTIMP.2013.10.008\u003c/span\u003e\u003cspan address=\"10.1016/J.INTIMP.2013.10.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlein M, Angstwurm K, Esser S, Hahn K, Maschke M, Scheithauer S, Schoefer H, Sturzenegger M, Wildemann B, Weber J (2020) German guidelines on the diagnosis and treatment of neurosyphilis. Neurol Res Pract 2020 2(1):1\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/S42466-020-00081-1\u003c/span\u003e\u003cspan address=\"10.1186/S42466-020-00081-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Almeida SM, Kussen GB, Cogo LL, Nogueira K (2022) Cerebrospinal fluid lactate as a predictive biomarker for tuberculous meningitis diagnosis. Diagnosis, Dec 8;10(2):130\u0026ndash;139. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1515/dx-2022-0102\u003c/span\u003e\u003cspan address=\"10.1515/dx-2022-0102\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 36476307\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarks M, Lawrence D, Kositz C, Mabey D (2018) Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review. Sex Transm Infect 94(8):585\u0026ndash;588. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/SEXTRANS-2018-053666\u003c/span\u003e\u003cspan address=\"10.1136/SEXTRANS-2018-053666\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamachandran PS, Wilson MR (2020) Metagenomics for neurological infections \u0026mdash; expanding our imagination. Nat Reviews Neurol 2020 16(10):547\u0026ndash;556. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41582-020-0374-y\u003c/span\u003e\u003cspan address=\"10.1038/s41582-020-0374-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurovirology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"njiv","sideBox":"Learn more about [Journal of NeuroVirology](http://link.springer.com/journal/13365)","snPcode":"13365","submissionUrl":"https://submission.nature.com/new-submission/13365/3","title":"Journal of NeuroVirology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"neurosyphilis, central nervous system, cerebrospinal fluid, diagnosis, HIV","lastPublishedDoi":"10.21203/rs.3.rs-3673645/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3673645/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n=42), presumptive NS (n=74), systemic syphilis (SS) (n=38), serological diagnosis of syphilis (n=18), PWH without SS and NS (n=10), and negative control (n=72). In PWoH, for presumptive NS, the combination of CSF TP \u0026gt;45 mg/dL and/or WBC \u0026gt;5.0 cells/mm\u003csup\u003e3\u003c/sup\u003e is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS. In PWoH, the value of CSF TP \u0026gt;45 mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count \u0026gt;20 cell/mm\u003csup\u003e3\u003c/sup\u003e, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of \u0026gt;10 or \u0026gt;20 cells/mm\u003csup\u003e3\u003c/sup\u003e, was moderately applicable for screening. As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, being better in the former. However, these biomarkers could be included for presumptive NS diagnosis. Additionally, the DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Cerebrospinal fluid biomarkers of symptomatic neurosyphilis in people with HIV compared with uninfected individuals","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 02:09:19","doi":"10.21203/rs.3.rs-3673645/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-16T14:22:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-13T20:44:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"af1f3432-b4e6-4c96-a8a5-07b8aa5c7e94","date":"2024-01-16T20:11:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-15T16:48:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-15T16:45:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-28T16:06:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of NeuroVirology","date":"2023-11-27T19:43:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurovirology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"njiv","sideBox":"Learn more about [Journal of NeuroVirology](http://link.springer.com/journal/13365)","snPcode":"13365","submissionUrl":"https://submission.nature.com/new-submission/13365/3","title":"Journal of NeuroVirology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"879eeb39-f3c9-4963-827b-3a759dc2fd20","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-03-01T17:54:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 02:09:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3673645","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3673645","identity":"rs-3673645","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}