Gui-Li Liu

Factors Associated with Serological Cure and the Serofast State of HIV-Negative Patients with Primary, Secondary, Latent, and Tertiary Syphilis

Background Some syphilis patients remain in a serologically active state after the recommended therapy. We currently know too little about the characteristics of this serological response. Methods We conducted a cohort study using the clinical database from Zhongshan Hospital, Medical College of Xiamen. In total, 1,327 HIV-negative patients with primary, secondary, latent, and tertiary syphilis were enrolled. Bivariate and multivariate analyses were utilised to identify factors associated with a serological cure and serofast state in syphilis patients one year after therapy. Chi-square tests were used to determine the differences in the serological cure rate across different therapy time points. Results One year after the recommended therapy, 870 patients achieved a serological cure, and 457 patients (34.4%) remained in the serofast state. The serological cure rate increased only within the first 6 months. The bivariate analysis indicated that male or younger patients had a higher likelihood of a serological cure than female or older patients. Having a baseline titre ≤1∶2 or ≥1∶64 was associated with an increased likelihood of a serological cure. The serological cure rate decreased for the different disease stages in the order of primary, secondary, latent, and tertiary syphilis. A distinction should be drawn between early and late syphilis. The multivariate analysis indicated that a serological cure was significantly associated with the disease phase, gender, age, and baseline rapid plasma reagin (RPR) titre. Conclusions The serofast state is common in clinical work. After one year of the recommended therapy, quite a few syphilis patients remained RPR positive. The primary endpoint of the study indicated that disease phase, gender, age and baseline RPR titre were crucial factors associated with a serological cure.

Clinical Spectrum of Neurosyphilis among HIV-Negative Patients in the Modern Era

Background: The clinical spectrum of neurosyphilis (NS) has changed over time. Objective: To describe the clinical spectrum and characteristics of NS in HIV-negative patients. Methods: A retrospective chart review was performed for 149 in patients with NS. Result: All patients were >25 years old, including 16.8% asymptomatic for NS, 15.4% with syphilitic meningitis, 24.2% with meningovascular NS, 38.9% with general paresis, 4.0% with tabes dorsalis and 0.7% with gummatous NS. The original misdiagnosis rate was 84.6%. All 149 patients had positive serum Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR). The overall positive rates of cerebrospinal fluid RPR (CSF-RPR) and CSF-TPPA were 57.0 and 89.9%, respectively. CSF pleocytosis and elevated CSF protein were found in 40.3% of patients. Nonspecific abnormal brain magnetic resonance imaging and electroencephalography findings were present in 60.4 and 54.8% of NS patients, respectively. Conclusions: NS has various clinical manifestations, laboratory findings and magnetic resonance imaging and electroencephalography findings, but all studies lack specificity. Every patient with neurological or psychiatric symptoms that are without unambiguous causes should have blood tests for syphilis. When serology proves positive, patients should undergo CSF examination.

Further evaluation of the characteristics of Treponema pallidum–specific IgM antibody in syphilis serofast reaction patients

Syphilis serofast reaction (SSR) is common in clinical work. From June 2005 to May 2009, 1208 syphilis patients were chosen for research by the Xiamen Center of Clinical Laboratory in China. Serologic tests were performed with toluidine red unheated serum test (TRUST) and Treponema pallidum particle agglutination (TPPA). Then, T. pallidum-specific IgM antibody (TP-IgM) was detected with fluorescent treponemal antibody absorption (FTA-Abs) and TPPA. In this study, patients were divided into the following experimental groups according to the results of TRUST and TPPA: (1) the SSR group consisted of 411 cases with (+) TRUST and (+) TPPA, and without clinical manifestations after 1 year of recommended syphilis treatment; (2) the serum cure group, which was further subdivided into group A consisting of 251cases with (-) TRUST and (+) TPPA; (3) group B consisting of 546 cases with (-) TRUST and (-) TPPA; and (4) the blood donor control group which consisted of 100 cases. We demonstrated that a total of 136 cases (33.09%) of 411 SSR patients were TP-IgM positive by TPPA, and this percentage was markedly higher than that in serum cure group A (9.16%). FTA-Abs analyses revealed similar results. All samples in serum cure group B and the control group were TP-IgM negative, which is identical to our previous report. The present study also indicated that the TP-IgM positive rate was not significantly different among patients with different ages, genders, and clinical phases after 1 year of recommended therapy. From the total of 1208 syphilis patients, 289 were randomly selected for TP-DNA detection by fluorescence quantitative polymerase chain reaction, and the positive rate of TP-DNA was 32.53%, which was slightly higher than that of FTA-Abs TP-IgM, and no statistically significant difference by chi-square tests, indicating the TP-DNA result is preferably consistent with FTA-Abs and supporting our deduction that TP-IgM could be used as a serologic marker for the relapse and infection of syphilis.

Screening of the Salmonella paratyphi A CMCC 50973 strain outer membrane proteins for the identification of potential vaccine targets.

Outer membrane protein antigens usually have strong immunogenicities, closely interact with the immune system and play a significant role in the development of new vaccines. The outer membrane proteins of Salmonella paratyphi A (S. paratyphi A) were screened for immunogenicity and immunoprotection for potential vaccine targets. In this study, the bactericidal effect of antiserum against the total outer membrane proteins of S. paratyphi A CMCC 50973 strain was determined, and their immunoprotection was detected with a challenge experiment on vaccinated mice. The immunogenic outer membrane proteins were identified via immunoproteomic technology, and recombinant outer membrane proteins were expressed and purified. The immunoprotection provided by the immunogenic membrane proteins was verified through active and passive immunity challenge experiments. The result revealed a number of S. paratyphi A outer membrane proteins that were proven as strong protective antigens. Twelve immunogenic outer membrane proteins were located and identified. Five recombinant proteins (LamB, pagC, TolC, nmpC and fadL) with strong immunoprotective abilities were found via the active immunity challenge experiment, with protection rates of 95, 95, 85, 80 and 70%, respectively. They were also proven to induce good immunoprotection via the passive immunity challenge experiment, with protection rates of 65, 55, 60, 55 and 50%, respectively. The immunoprotective rate of the five-antiserum combination was 85%. In conclusion, the LamB, pagC, TolC, nmpC and fadL outer membrane proteins, with strong immunogenicities and immunoprotection, are effective protein candidate targets for the development of new vaccines, whereas the recombinant outer membrane proteins are a promising tool for improving immunoprotection.

Spectrum and characterization of movement disorders secondary to neurosyphilis.

There have been frequent reports of Neurosyphilis with atypical features. Syphilitic infection of the central nervous system can result in various movement disorders (MD). The few reports of MD patients with neurosyphilis have been mainly of single patient. Between June 2005 and February 2012 we identified, 169 in-patients with neurosyphilis at Zhongshan Hospital. We performed a retrospective chart review to characterize MD findings, clinical signs and symptoms, misdiagnosis rate, laboratory findings, and brain magnetic resonance imaging results. We found that seven of the 169 neurosyphilis patients presenting with MD, had originally been misdiagnosed with Parkinsonism (4), laryngeal dystonia (1), corticobasal syndrome (1), and sensory ataxia (1). None of these patients were initially suspected of having neurosyphilis. The correct diagnosis was syphilitic meningitis (1), meningovascular neurosyphilis (2), general paresis (3), and tabes dorsalis (1). Among them, six patients had abnormal imaging studies, and sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all seven patients were positive. The cerebrospinal fluid (CSF) examinations showed that four patients were CSF-RPR positive (titers ≤1:16) by CSF syphilitic serologic testing, but all seven patients were CSF-TPPA reactive. Moreover, two patients had CSF pleocytosis and four patients had elevated CSF protein expression. Our findings reinforced the importance of routine serologic testing for syphilis should be a part of the evaluation of patients with atypical MD presentations or in whom alternative diagnoses are not forthcoming. When serology is positive, all patients should be examined more thoroughly for neurosyphilis by lumbar puncture.

Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom

A retrospective chart review was performed to characterize the clinical presentation, the characteristic combination of serologic and cerebrospinal fluid (CSF) abnormalities, and the neuroimaging findings of neurosyphilis (NS) patients who had epileptic seizures alone as an initial presenting symptom. In a 6.75-year period, 169 inpatients with NS were identified at Zhongshan Hospital (from June 2005 to February 2012). We demonstrated that 13 (7.7%) of the 169 NS patients had epileptic seizures alone as an initial presenting feature. Epileptic seizures occurred in NS patients with syphilitic meningitis (2 cases), meningovascular NS (5 cases), and general paresis (6 cases). The types of epileptic seizures included simple partial, complex partial with secondary generalization (including status epilepticus), and generalized seizures (no focal onset reported). Nine of NS patients with only epileptic seizures as primary symptom were misdiagnosed, and the original misdiagnosis was 69.23% (9/13). Ten (10/13, 76.9%) patients had an abnormal magnetic resonance imaging, and 7 (7/13 53.8%) patients had abnormal electroencephalogram recordings. In addition, the sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all 13 patients were positive. The overall positive rates of the CSF-RPR and CSF-TPPA were 61.5% and 69.2%, respectively. Three patients demonstrated CSF pleocytosis, and 9 patients exhibited elevated CSF protein levels. Therefore, NS with only epileptic seizures at the initial presentation exhibits a lack of specificity. It is recommended that every patient with clinically evident symptoms of epileptic seizures should have a blood test performed for syphilis. When the serology results are positive, all of the patients should undergo a CSF examination to diagnose NS.

Psychiatric Manifestations as Primary Symptom of Neurosyphilis Among HIV-Negative Patients

This study characterizes psychiatric manifestations as a primary symptom of neurosyphilis (NS). Fifty-two of the 169 NS patients presented with psychiatric manifestations, many patients had characteristics of more than one syndrome, including cognitive impairment, personality disorders, delirium, hostility, dysarthria, confusion, disruption of their sleep-wake cycle, fecal and urinary incontinence, dysphoria, paranoia, hallucinations, expansive mood, and mania. Fifty-two patients had positive sera RPR and T. pallidum particle agglutination (TPPA), 75% had positive CSF RPR, 96.2% had positive CSF TPPA, 44.2% had CSF pleocytosis and elevated CSF proteins, and 70.0% had nonspecific, abnormal brain MRIs. These results indicate that NS mimics almost all psychiatric disorders.

Neuropsychiatric disorders secondary to neurosyphilis in elderly people: one theme not to be ignored

BACKGROUND Neurosyphilis (NS) may present with neuropsychiatric disorders characterized by cognitive impairment, personality disorders, and confusion, among others. Very few studies have focused on neuropsychiatric disorders secondary to NS in elderly people. METHOD A retrospective chart review was performed to characterize the psychiatric findings, clinical signs and symptoms, laboratory findings, and brain magnetic resonance imaging results of ten elderly inpatients with NS. RESULTS In these ten patients, the most common presenting symptoms included a wide variety of psychiatric manifestations. The serum rapid plasma regain (RPR) and Treponema pallidum particle agglutination assay (TPPA) of the ten patients were positive, with positive CSF TPPA and RPR rates of 100% and 60%, respectively. In addition, 90% of the patients demonstrated abnormal imaging, including cerebral atrophy, infarct ischemic stroke, and hydrocephalus. CONCLUSIONS Our findings support the importance of serological tests for syphilis as a routine component of the evaluation of patients with clinically evident neurological or psychiatric symptoms. If the serology is positive, all of the patients should be examined with a lumbar puncture. Moreover, psychiatric illnesses secondary to NS in the elderly also deserve medical attention.

Analysis of lymphocyte subsets in HIV-negative neurosyphilis patients

It is unclear how Treponema pallidum affects the immune response among various lymphocyte subsets in neurosyphilis patients with different clinical stages. In order to determine the immune response by T. pallidum infection, we detected the peripheral blood lymphocyte subsets among 14 asymptomatic neurosyphilis patients, 19 early neurosyphilis patients, 9 late neurosyphilis patients, and 50 healthy persons. The result indicated that the number of CD3+CD8+ lymphocytes was significantly higher in neurosyphilis patients than in the control group (χ(2) = 4.427, P = 0.035). The number of CD3+CD8+ lymphocytes was significantly higher in the asymptomatic neurosyphilis group than in the early neurosyphilis group, late neurosyphilis group, and control group (F = 4.644, P = 0.005). The number of NK cells was significantly lower in neurosyphilis patients than in the control group (χ(2) = 13.226, P = 0.000). The number of NK cells in neurosyphilis patients with different clinical stages was also lower than in the control group (F = 4.402, P = 0.006). The number of CD3+ lymphocytes, CD3+CD4+ lymphocytes, and B lymphocytes had no difference among the 4 groups. The results indicated that the progression of neurosyphilis may be related to the continued reduction in the number of NK cells and to the continued increase in CD3+CD8+ lymphocytes.

Characteristics of patients suffering from cow milk allergy

The most frequent symptoms among the manifestations of cow milk allergy (CMA) are gastrointestinal. CMA pathogenesis involves immunological mechanisms with participation of immunocompetent cells, production of immunoglobulin E (IgE) and immunoglobulin G (IgG). We aim to determine whether cow milk-specific IgE antibodies coexist with cow milk-specific IgG antibodies in CMA patients with diarrhea symptom, and if there is any relationship between both antibody types. 65 CMA patients (average age of 17 years, ranging from 2 to 74 years), all of who had diarrhea symptom of CMA, were enrolled in this study. The total cow IgE and IgG subclass in serum were measured by electrochemiluminescence immunoassay and rate immune scatter turbidimetry, respectively. And also the cow milk-specific IgE was determined by enzyme-linked immunosorbent assay. The number of eosinophils in serum was calculated by Sysmex XE-2100 Hematology Analyzer. Our data showed that both cow milk-specific IgG and IgE levels were significantly elevated in CMA patients compared to those of age-matched control subjects. Out of the 65 CMA patients, 40 showed elevated cow milk-specific IgE antibody level, among which, 28 cases presented highly sensitive reaction to cow milk-specific IgG, along with each six of moderate and mild sensitive reaction to cow milk-specific IgG; while 20 showed elevated total IgG levels. The IgG3 positive rate was 16.9%, which was the highest. A moderate correlation between cow milk-specific IgE and cow milk-specific IgG was found in the CMA patients (r=0.415, P=0.001). The results indicated that cow milk-specific IgE antibodies could coexist with cow milk-specific IgG antibodies in patients suffering from CMA. The aberrant changes in the concentration of cow milk-specific IgE antibodies were associated with cow milk-specific IgG antibodies.