Immunization with nontreponemal antigen alters the course of experimental syphilis in the rabbit model.

The role of nontreponemal antibodies in the Treponema pallidum infection course is unclear. We investigated the effect of immunization with nontreponemal antigen on T. pallidum-challenged rabbits. Nontreponemal antigen was injected intravenously into rabbits in the nontreponemal group (n = 12) to elicit antibodies (≥1:64), and normal saline-injected rabbits were used as controls (n = 12). Then, rabbits were challenged with 106T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for mRNA analysis every week. Six rabbits from both groups were euthanized at 14 d and 28 d. The popliteal lymph nodes were extracted to assess infectivity using a rabbit infectivity test. The maximum lesion diameters were not different between the two groups (12.4 ± 0.9 mm in the nontreponemal group vs. 12.5 ± 1.0 mm in the control group, P = 0.386), but the time to maximum diameter appearance was delayed by approximately 4 d in the nontreponemal group (14.4 ± 1.6 d vs. 10.8 ± 1.9 d, P = 0.000). There were no significant differences in the proportions of lesions (58/60 (96.7%) vs. 59/60 (98.3%), P = 0.500) or ulcers (55/60 (91.7%) vs. 57/60 (95.0%), P = 0.359) between the two groups. An ulcer development delay of 5 d was observed in the nontreponemal group (19.3 ± 2.0 d vs. 14.0 ± 1.8 d, P = 0.000). IL-2 and IFN-γ mRNA expression in the nontreponemal group was significantly higher than that in the control group at 7 d and 14 d post-challenge. flaA mRNA expression and the rabbit infectivity test positive rate were not different between the two groups. Immunization with nontreponemal antigen altered the syphilis course in rabbits, resulting in delayed maximal lesion diameter and ulcer development, but it could not inhibit the spread of T. pallidum from primary lesion sites to viscera.

A chemiluminescence immunoassay for the detection of NT-proBNP.

BACKGROUND: The aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP. METHODS: The within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay. RESULTS: The total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP -4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86-0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85-0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with ">40000 pg/ml". CONCLUSIONS: The HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice.

Comparison of electrolyte and glucose levels measured by a blood gas analyzer and an automated biochemistry analyzer among hospitalized patients.

BACKGROUND: Blood gas analyzers are capable of delivering results on electrolytes and metabolites within a few minutes and facilitate clinical decision-making. However, whether the results can be used interchangeably with values measured by chemistry analyzers remains controversial. Blood gas analyzers are capable of delivering results on electrolytes and metabolites within a few minutes and facilitate clinical decision-making. However, whether the results can be used interchangeably with values measured by chemistry analyzers remains controversial. METHODS: In total, arterial and matched venous blood samples were collected from 200 hospitalized patients. Arterial blood samples were evaluated using a RAPIDPOINT 500 to test electrolyte and glucose levels, then the samples were centrifuged and the same parameters were measured with an AU5800. Venous blood samples were processed and tested in accordance with standard operation procedures. Data were compared by using a paired t test, the agreement between the two analyzers was evaluated by using the Bland-Altman test, and sensitivity and specificity were calculated. RESULTS: Paired t tests showed that all parameters tested were significantly different between the two analyzers except chloride. The biases calculated indicated that blood gas analyzers tend to underestimate the parameters, and the linear regression showed a strong correlation between the two analyzers. The sensitivity, specificity and kappa values demonstrated that the diagnostic performance of blood gas analyzers is not satisfactory. CONCLUSION: The significant reduction in parameter estimation and diagnostic performance we observed suggested that clinicians should interpret results from blood gas analyzers more cautiously. The reference interval of blood gas analyzers should be adjusted accordingly, given that values are underestimated.

The P2X7 receptor mediates NLRP3-dependent IL-1ß secretion and promotes phagocytosis in the macrophage response to Treponema pallidum.

It is unclear whether P2X7 receptor (P2X7R) mediates NOD-like receptor family protein 3 (NLRP3)-dependent IL-1ß secretion and spirochete phagocytosis in syphilis. This study was conducted to investigate the role of P2X7R in modifying NLRP3-dependent IL-1ß secretion and regulating phagocytosis by Treponema pallidum (T. pallidum)-induced macrophages. Macrophages derived from a human acute monocytic leukemia cell line were cultured with T. pallidum. The activation of P2X7R in T. pallidum-treated macrophages occurred in a dose- and time-dependent manner. The P2X7R silencing group showed significantly decreased NLRP3 mRNA and protein levels (vs. the Tp group, P < 0.001). Similar results were observed for IL-1ß secretion using ELISA (vs. the Tp group, P < 0.001). Furthermore, P2X7R siRNA transfection significantly decreased the percentage of spirochete-positive macrophages (29.73% vs. 70.83%, P < 0.001) and spirochete internalization (mean fluorescence intensity (MFI), 9.20 vs. 19.39, P < 0.001). This finding revealed that P2X7R played a role in the induction of NLRP3-dependent IL-1ß secretion by T. pallidum-induced macrophages. Furthermore, we found that P2X7R plays an important role in IL-1ß secretion and in the promotion of T. pallidum phagocytosis by macrophages. These results may not only contribute to our understanding of the immune mechanism that is active during T. pallidum infection but may also lay the groundwork for strategies to combat syphilis.

Molecular Characterization Based on MLST and ECDC Typing Schemes and Antibiotic Resistance Analyses of Treponema pallidum subsp. pallidum in Xiamen, China.

In total, 49 clinical samples were analyzed using two typing schemes, Enhanced Centers for Disease Control and Prevention (ECDC) and multilocus sequence typing (MLST), to describe the molecular characteristics of circulating Treponema pallidum isolates in Xiamen between 2016 and 2017. In addition, genetic mutations potentially related to antibiotic resistance of T. pallidum were also analyzed. Forty five samples were fully typed by ECDC, and 14 different subtypes were detected. The most common subtype was 16d/f (24.4%), followed by 14d/f (20.0%). All forty nine samples were successfully typed by MLST, while only four allelic profiles were identified, including three SS14-like profiles and one Nichols-like profile. Among them, the major allelic profile was 1.1.8 (85.7%). Interestingly, the allelic profile 1.3.1 widespread in Europe and North America was not detected in this region. Additionally, A2058G mutation in 23S rRNA was found in all detectable samples (38/38), and no mutation in 16S rRNA was observed (36/36). Four non-synonymous single-nucleotide polymorphisms in penicillin-binding protein genes were found in the 35 samples eligible for Sanger sequencing. Among them, the variant in tp0500 (P564I) can only be found in the SS14-like isolates. Homoplastic changes in tp0760 (I415F/I415M) and tp0705 (A506V/A506T) were found. Moreover, the variant tp0705 A506V and the variant tp0705 A506T separately appeared in the SS14-like isolates and Nichols-like isolates, respectively. This study showed that the genotypes of T. pallidum isolates in Xiamen between 2016 and 2017 were different from those in other geographic areas. The resistance-related variants of T. pallidum isolates identified in this study could provide awareness for clinicians in the treatment of syphilis.

Comparison of Clinical and Laboratory Characteristics of General Paresis and Non-Neurosyphilis Dementia.

BACKGROUND: The differential diagnosis of general paresis (GP) and non-neurosyphilis (NS) dementia is not clearly defined. The present study examined the differences in clinical and laboratory features of GP and non-NS dementia. MATERIALS AND METHODS: We retrospectively examined clinical and laboratory features of 85 GP patients and 196 non-NS dementia patients. Data were collected from Zhongshan Hospital between June 2005 and June 2014. RESULTS: The GP group had a higher percentage of males (83.53%, 71/85) and younger median age ([52 [interquartile range 47.0-61.0] vs. 76 [68.3-82.0] years) than the non-NS dementia group. GP have higher Mini-Mental State Examination (MMSE; Z = -5.809; p = 0.000) than non-NS dementia. Distribution of CDR scores were significantly higher in the non-NS group than GP group (χ2 = 29.153; p = 0.000). The laboratory findings showed significantly different total cholesterol (CH), low-density lipoprotein CH and homocysteine levels between the 2 groups. Serologic testing for syphilis revealed that the GP group had higher seropositive rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) rates than the non-NS dementia group (96.47% [82/85] vs. 0.51% [1/196], Z = -2.663, p = 0.008; 100% [85/85] vs. 1.02% [2/196], Z = -2.663, p = 0.008). Interestingly, cerebrospinal fluid (CSF) biochemical indices, including pleocytosis rates, increased protein levels, and positive RPR and TPPA rates in the GP group were higher than that in the non-NS dementia group. CONCLUSIONS: Based on these preliminary data, patients with clinically evident symptoms of dementia, especially middle-aged males, should undergo blood tests for syphilis. All patients with positive serology results should undergo CSF examinations to diagnose GP dementia before further pharmaceutical and behavioral interventions.

Treponema pallidum promotes macrophage polarization and activates the NLRP3 inflammasome pathway to induce interleukin-1ß production.

BACKGROUND: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1ß production and its influence on macrophage polarization triggered by T. pallidum. RESULTS: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1ß secretion in T. pallidum-treated macrophages, and the observed production of IL-1ß occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1ß by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1ß release from T. pallidum-treated macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1ß secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1ß production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.

The characteristics of beta 2-glycoprotein I-dependent anticardiolipin antibody and blood coagulation status in subjects with classical biological false-positive syphilis reactions.

Anticardiolipin antibody (ACA) includes beta2-glycoprotein I-dependent (ß2-GPI-dependent) and ß2-GPI-independent forms. The appearance of ß2-GPI-dependent ACA and its association with blood coagulation have never been investigated in subjects with classical biological false-positive syphilis reactions (CBFP). In total, 146 CBFP subjects, 465 syphilis patients and 64 presumed antiphospholipid antibody syndrome (pAPS) patients were enrolled, and ß2-GPI-dependent ACA IgA/IgG/IgM and anti-ß2-GPI IgA/IgG/IgM antibodies were detected via chemiluminescence assay. Conventional blood coagulation indices were measured to analyze their associations with these autoantibodies. In current study, the positive rate of ß2-GPI-dependent ACA in CBFP subjects was 22.60%, which was significantly higher than that in syphilis patients (3.87%) (P < 0.001) and similar to that in pAPS patients (32.81%) (P = 0.119). The predominant autoantibody isotypes were IgG in CBFP subjects and pAPS patients and IgM in syphilis patients. Positive autoantibody rates were independent of rapid plasma reagin titers. CBFP and pAPS subjects had longer prothrombin times (P < 0.001) and activated partial thromboplastin times (APTTs, P < 0.001) but lower fibrinogen concentrations (P = 0.022) and platelet counts (P < 0.001) than syphilis patients. APTTs were prolonged in CBFP, syphilis and pAPS subjects with positive autoantibodies compared with those in subjects with negative autoantibodies (P < 0.05). In conclusion, ACAs in CBFP and syphilis subjects are heterogeneous; ß2-GPI-dependent ACA constitutes a significant proportion of ACAs in CBFP subjects, while ß2-GPI-independent ACA predominates in syphilis patients. CBFP subjects are more prone to blood coagulation disorders than syphilis patients, and these autoantibodies may impact the intrinsic coagulation cascade in CBFP subjects, similar to pAPS patients.

Assessing effects of different processing procedures on the yield of Treponema pallidum DNA from blood.

In this work, we employed real-time PCR analysis targeting tp0574 to investigate the effects of different processing procedures on the yield of T. pallidum DNA from blood to improve assay sensitivity. The T. pallidum DNA yields following red blood cell lysis pretreatment were 40.4 times greater from whole blood and 32.4 times greater from residual hematocytes than yields without pretreatment. For the simulated whole-blood experiments, the T. pallidum DNA yields from the lower layer were 2.8, 4.6, 7.3, 12.6, 15.24, 16.7, 65.1 and 73.1 times those from the upper layer following centrifugation at 500×, 1000×, 2000×, 4000×, 5000×, 7000×, 10,000× and 20,000 × g, respectively. However, the T. pallidum DNA yields from blood clots were only 1.0% at different centrifugal forces. The experiment with infected rabbit blood showed results similar to those mentioned above. In addition, sample processing time (within 48 h) and storage temperature (4 °C and 25 °C) did not affect T. pallidum DNA extraction efficiency. The T. pallidum DNA yield can be significantly improved by red blood cell lysis pretreatment and appropriate centrifugation. Furthermore, the T. pallidum DNA extraction yield is greater from whole blood or residual hematocytes from anti-coagulated blood than from plasma, serum or blood clots.

Origin of Nontreponemal Antibodies During Treponema pallidum Infection: Evidence From a Rabbit Model.

The origin of nontreponemal antibodies during syphilis infection is hotly debated. Here, we analyzed the immune response in rabbits immunized with various antigens. Inactivated treponemes elicited the production of low-titer nontreponemal antibodies in some rabbits. Cardiolipin combined with bovine serum albumin also induced anticardiolipin antibody production. These findings indicate that Treponema pallidum contained a cardiolipin antigen with weak immunogenicity. However, active T. pallidum induced higher nontreponemal antibody production with strong immunogenicity at an earlier time point, and the antibody titer was consecutive, suggesting the high nontreponemal antibody titer resulted from the combined effects of both the T. pallidum cardiolipin antigen and the damaged host-cell cardiolipin antigen during syphilis infection, the latter of which plays a major role in the induction of nontreponemal antibody production. Our study provides direct animal evidence of the origin of nontreponemal antibodies during T. pallidum infection.

Akt, mTOR and NF-κB pathway activation in Treponema pallidum stimulates M1 macrophages.

The polarization of macrophages and the molecular mechanism involved during the early process of syphilis infection remain unknown. This study was conducted to explore the influence of Treponema pallidum (T. pallidum) treatment on macrophage polarization and the Akt-mTOR-NFκB signaling pathway mechanism involved in this process. M0 macrophages derived from the phorbol-12-myristate-13-acetate-induced human acute monocytic leukemia cell line THP-1 were cultured with T. pallidum. T. pallidum induced inflammatory cytokine (IL-1ß and TNF-α) expression in a dose- and time-dependent manner. However IL-10 cytokine expression decreased at the mRNA and protein levels. Additionally, the expression of the M1 surface marker iNOS was up-regulated with incubation time, and the expression of the M2 surface marker CD206 was low (vs. PBS treated macrophages, P < 0.001) and did not fluctuate over 12 h. Further studies revealed that Akt-mTOR-NFκB pathway proteins, including p-Akt, p-mTOR, p-S6, p-p65, and p-IκBα, were significantly higher in the T. pallidum-treated macrophages than in the PBS-treated macrophages (P < 0.05). In addition, inflammatory cytokine expression was suppressed in T. pallidum-induced M1 macrophages pretreated with LY294002 (an Akt-specific inhibitor) or PDTC (an NF-κB inhibitor), while inflammatory cytokine levels increased in T. pallidum-induced M1 macrophages pretreated with rapamycin (an mTOR inhibitor). These findings revealed that T. pallidum promotes the macrophage transition to pro-inflammatory M1 macrophages in vitro. The present study also provides evidence that Akt, mTOR and NF-κB pathway activation in T. pallidum stimulates M1 macrophages. This study provides novel insights into the innate immune response to T. pallidum infection.

Development of tissue inflammation accompanied by NLRP3 inflammasome activation in rabbits infected with Treponema pallidum strain Nichols.

BACKGROUND: The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum. METHODS: Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1ß (IL-1ß) mRNA analysis during infection. Blood was also collected for the determination of IL-1ß concentration. RESULTS: Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1ß secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to "normal" levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1ß mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1ß expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1ß in the testes of the infected rabbits. CONCLUSIONS: This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.

Whole genome sequence of the Treponema pallidum subsp. pallidum strain Amoy: An Asian isolate highly similar to SS14.

Treponema pallidum ssp. pallidum (T. pallidum), the causative agent of the sexually transmitted disease syphilis, is an uncultivatable human pathogen. The geographical differences in T. pallidum genomes leading to differences in pathogenicity are not yet understood. Presently, twelve T. pallidum genomes are available to the public, all of which are American in origin and often co-infect patients with human immunodeficiency virus (HIV). In this study, we examined the T. pallidum subsp. pallidum strain Amoy, a syphilis pathogen found in Xiamen, China. We sequenced its genome using Illumina next-generation sequencing technology and obtained a nearly (98.83%) complete genome of approximately 1.12 Mbps. The new genome shows good synteny with its five T. pallidum sibling strains (Nichols, SS14, Mexico A, DAL-1, and Chicago), among which SS14 is the strain closest to the Amoy strain. Compared with strain SS14, the Amoy strain possesses four uncharacterized strain-specific genes and is likely missing six genes, including a gene encoding the TPR domain protein, which may partially account for the comparatively low virulence and toxicity of the Amoy strain in animal infection. Notably, we did not detect the 23S rRNA A2058G/A2059G mutation in the Amoy strain, which likely explains the sensitivity of Amoy strain to macrolides. The results of this study will lead to a better understanding of the pathogenesis of syphilis and the geographical distribution of T. pallidum genotypes.

Re-evaluating the sensitivity of the rabbit infectivity test for Treponema pallidum in modern era.

BACKGROUND: The rabbit infectivity test (RIT) was previously described as a highly-sensitive method for clinically detecting Treponema pallidum. But our primary study indicated this result may have changed in current antibiotics era. METHODS: By inoculating rabbits testis with cerebrospinal fluid (CSF) (n=63) and exudate from hard chancre lesions (n=13), we re-evaluated the sensitivity of RIT in modern era. All isolated T. pallidum strains from the RIT were performed for the strain type based on "CDC subtype/tp0548" method. Chi-square and Fisher's exact tests were used to determine the statistical significance of differences across data sets. RESULTS: Result indicated that 2 of 63 CSF (2/63, 3.17%) and 5 of 13 lesion exudate samples (5/13, 38.47%) were positive in the RIT, with a much longer time to detection for CSF samples. Only 1 of 28 samples from patients who admitted treatment with antibiotics prior to clinical exam was positive in the RIT; while 6 of 48 patients, who admitted no recent exposure to antibiotics or was unclear about the medical history, were positive in RIT. DNA sequence analysis revealed 6 strains of 14d/f subtype and one strain of 14a/f subtype. CONCLUSIONS: In conclusions, RIT is no longer a highly sensitive method for detecting T. pallidum in clinical samples as before, and is not inadequately considered to be a reference method for measuring the sensitivity of other new methods, such as the PCR. These data represent the first reexamination of the sensitivity of RIT in the post-antibiotic era with a large clinical sample.

Macrophage migration inhibitory factor as a novel cerebrospinal fluid marker for neurosyphilis among HIV-negative patients.

BACKGROUND: Neurosyphilis (NS) is difficult to diagnose, especially in syphilis patients with negative cerebrospinal fluid (CSF) rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) tests. METHODS: We conducted a cross-sectional study and an analysis of macrophage migration inhibitory factor (MIF) in syphilitic patients to identify a novel marker for the diagnosis of NS, with a focus on probable NS (NS with negative VDRL/RPR tests). For this purpose, CSF and serum MIF concentrations were determined in 43 NS and 43 syphilis/non-NS (N-NS) patients at the Zhongshan Hospital of the Medical College of Xiamen University from July 2014 to June 2015. Sixty-three blood donors were used as healthy controls. RESULTS: NS patients had higher CSF (median [IQR]: 8.77ng/ml [4.76-19.13]) and serum (52.58ng/ml [28.31-95.94]) MIF concentrations than N-NS patients did (4.08 [2.21-9.68] and 34.30 [19.77-59.75], respectively). Using a cut-off point of 6.63ng/ml, CSF MIF had a sensitivity of 74.42% and a specificity of 67.74% for the diagnosis of NS. The sensitivity was higher than that of CSF RPR (39.53%) and increased protein (48.84%) tests and similar to that of CSF pleocytosis (67.44%). Additionally, the sensitivity of CSF MIF, which was 92.31% for the diagnosis of probable NS, was higher than that of CSF pleocytosis (65.38%) and increased protein (53.85%) tests. By integrating all CSF parameters (pleocytosis, increased protein and MIF), the sensitivity would be improved to 100% by parallel testing, which would avoid missed diagnoses. Moreover, the specificity would be improved to 100% by the serial testing algorithm, which would again avoid misdiagnosis. CONCLUSIONS: CSF MIF concentrations can be used as a novel CSF marker to establish or exclude a diagnosis of NS.

A negative nontreponemal and/or specific antitreponemal IgM test does not exclude active infectious syphilis: evidence from a rabbit infectivity test: A case report.

BACKGROUND: The diagnostic criteria for active infectious syphilis in the clinic are important matter of controversy and debate. So far, clinicians habitually do use the negative results of the nontreponemal and/or the specific antitreponemal IgM as the evidences of disease-free or active infection-free status. METHOD: We present a case study involving a patient who was admitted to Zhongshan Hospital because of cerebral infarct. Clinical examination indicated he had a history of latent syphilis with negative nontreponemal and specific antitreponemal IgM tests. The cerebrospinal fluid sample from the patient was inoculated into seronegative New Zealand rabbit. RESULTS: Motile Treponema pallidum was detected by a rabbit infectivity test in the patient's cerebrospinal fluid. This syphilis strain was confirmed by DNA subtyping form of "centers for disease control subtype/tp0548 sequence type", and the strain type was 14d/f. Treatment with benzathine penicillin provided no apparent benefit, but treatment with aqueous crystalline penicillin G, especially recommended for neurosyphilis, led to disease regression. No evidence of cerebral infarct was observed during a 2-year follow-up period. CONCLUSION: The definitive differential diagnosis of active infectious syphilis should be reconsidered. Moreover, selecting the appropriate penicillin preparation is important because T pallidum can reside in sequestered sites. It is necessary to treat a patient with known invasion of the central nervous system with aqueous crystalline penicillin G, if previous treatment for syphilis failed and patients had some clinical neurological presentation that is otherwise unexplained, but that could represent neurosyphilis. Additional studies are needed to confirm the results in other syphilis patients.

Clinical and laboratory characteristics in patients suffering from general paresis in the modern era.

BACKGROUND: No gold standard currently exists for the diagnosis of general paresis (GP), thus often resulting in unnecessarily delayed therapeutic decision. METHODS: A retrospective chart review was performed for 85 inpatients with GP in Zhongshan Hospital, Medical College of Xiamen University, and the characteristics of their clinical profiles, serum and cerebrospinal fluid (CSF) examinations, neuroimaging examination, and electroencephalogram (EEG) data were analyzed. RESULTS: Among the 85 GP patients, the clinical symptoms that were frequently observed upon admission included a variety of psychiatric-behavioral symptoms and varying degrees of cognitive impairment. All of the patients had positive serum Treponema pallidum particle agglutination (TPPA) assays, 96.47% of the patients had positive CSF TPPA assays, and 41.18% of the patients had both CSF pleocytosis and elevated CSF protein levels. Focal atrophy in one cerebral region or in multiple regions was evident in neuroimages. The EEG data primarily showed slightly abnormal EEG activity. CONCLUSION: These results demonstrate the complexity of the clinical characteristics of GP and highlight the importance of early diagnosis.

Evaluation of the boson chemiluminescence immunoassay as a first-line screening test in the ECDC algorithm for syphilis serodiagnosis in a population with a high prevalence of syphilis.

We developed a new Boson chemiluminescence immunoassay (CIA) and evaluated its application with cross-sectional analyses. Our results indicated that the Boson CIA demonstrated strong discriminatory power in diagnosing syphilis and that it can be used as a first-line screening test for syphilis serodiagnosis using the European Centre for Disease Prevention and Control algorithm or as a confirmatory test when combined with a patient's clinical history.