Song-Jie Huang

Analysis of 3 Algorithms for Syphilis Serodiagnosis and Implications for Clinical Management

BACKGROUND Algorithms for the diagnosis of syphilis continue to be a source of great controversy, and numerous test interpretations have perplexed many clinicians. METHODS We conducted a cross-sectional study of 24 124 subjects to analyze 3 syphilis testing algorithms: traditional algorithm, reverse algorithm, and the European Centre for Disease Prevention and Control (ECDC) algorithm. Every serum sample was simultaneously evaluated using the rapid plasma reagin, Treponema pallidum particle agglutination, and chemiluminescence immunoassay tests. With the results of clinical diagnoses of syphilis as a gold standard, we evaluated the diagnostic accuracy of the 3 syphilis testing algorithms. The κ coefficient was used to compare the concordance between the reverse algorithm and the ECDC algorithm. RESULTS Overall, 2749 patients in our cohort were diagnosed with syphilis. The traditional algorithm had the highest negative likelihood ratio (0.24), a missed diagnosis rate of 24.2%, and only 75.81% sensitivity. However, both the reverse and ECDC algorithms had higher diagnostic efficacy than the traditional algorithm. Their sensitivity, specificity, and accuracy were 99.38%-99.85%, 99.98%-100.00%, and 99.93%-99.96%, respectively. Moreover, the overall percentage of agreement and κ value between the reverse and the ECDC algorithms were 99.9% and 0.996, respectively. CONCLUSIONS Our research supported use of the ECDC algorithm, in which syphilis screening begins with a treponemal immunoassay that is followed by a second, different treponemal assay as a confirmatory test in high-prevalence populations. In addition, our results indicated that nontreponemal assay is unnecessary for syphilis diagnosis but can be recommended for determining serological activity and the effect of syphilis treatment.

Incidence and Risk Factors for the Prozone Phenomenon in Serologic Testing for Syphilis in a Large Cohort

BACKGROUND The prozone phenomenon is known to be associated with high antibody titers; other associations, such as host factors, have not been elucidated. METHODS A retrospective analysis was conducted to evaluate the incidence of the prozone phenomenon of the syphilis rapid plasma reagin (RPR) test among 46 856 clinical samples, between June 2010 and June 2013. Logistic regression was used to analyze the risk factors of the prozone phenomenon. RESULTS Our results showed that the incidence of the prozone phenomenon was low (0.83%) and could occur during any clinical phase, particularly during primary and secondary syphilis. Pregnancy and neurosyphilis were associated with the prozone phenomenon; sex, age, and whether the patient had been treated were not. The results also revealed that the prozone phenomenon not only occurred in patients with a high titer but also could occur in patients with a moderate/low titer. In fact, almost 31% of the patients with the prozone phenomenon had titers ≤1:16. CONCLUSIONS The prozone phenomenon in the RPR test was associated with the phase of syphilis, pregnancy, and neurosyphilis as well as a range of RPR titers between 1:8 and 1:512. This latter finding is in contrast to previous reports that the prozone phenomenon is associated with very high RPR titers.

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.

Characterization of the classical biological false-positive reaction in the serological test for syphilis in the modern era

To characterize the CBFP reaction in the modern era, we analyzed the results of parallel rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) tests from a total of 63,765 blood samples obtained at Zhongshan Hospital in the Medical College of Xiamen University from May 2008 to February 2013. Among the 63,765 tested blood samples, 206 (0.32%) had the CBFP reaction. In multivariate analysis, an increased likelihood of the CBFP reaction was associated with female subjects, subjects ≥80years old, and subjects between 16 and 35years old (P<0.05). The CBFP reaction occurred in association with 17 categories of disease, including 60 types of diseases, in the 206 subjects. To our knowledge, a number of these diseases had not been previously reported to be associated with the CBFP in the RPR test, including false labor, megaloblastic anemias, aplastic anemias, redundant prepuce, congenital malformation of heart, and salpingitis. Among the 206 patients with the CBFP reaction, 35 patients were subjected to follow-up for five years. 26 out of 35 these patients were at a 1:1 initial RPR titer, 8 out of 35 patients were at a 1:2 initial RPR titer, and 1 out of 35 patients were at a 1:4 initial RPR titer. 30 subjects had their RPR seroreverted. In our opinion, additional CBFP research using a large sample population will contribute to the identification of additional underlying serious disorders that are not related to syphilis. Such results could be useful for the prediction and diagnosis of these diseases.

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.

Association between neurosyphilis and diabetes mellitus: Resurgence of an old problem 神经梅毒与糖尿病的关系：“旧事”再现

Syphilis, a sexually transmitted disease, is commonly referred to as the “great imitator” because of its wide‐ranging clinical presentations. Recently, we noticed that patients with neurosyphilis (NS) seemed to be more susceptible to complications of diabetes mellitus (DM). This is an interesting phenomenon, but it also puzzles clinicians because of scant knowledge about this situation.

Association between neurosyphilis and diabetes mellitus: Resurgence of an old problem

Syphilis, a sexually transmitted disease, is commonly referred to as the “great imitator” because of its wide‐ranging clinical presentations. Recently, we noticed that patients with neurosyphilis (NS) seemed to be more susceptible to complications of diabetes mellitus (DM). This is an interesting phenomenon, but it also puzzles clinicians because of scant knowledge about this situation.

Laboratorial characteristics of patients with diarrhoea suffering from egg white allergy

BACKGROUND Egg allergy is associated with diarrhoeal symptoms. However, the mechanism underlying allergic diarrhoea remains unclear. OBJECTIVE To determine whether egg white-specific IgE antibodies coexist with egg white-specific IgG antibodies in patients with egg allergy featuring diarrhoeal symptoms, and whether there is any relationship between these two antibody types. METHODS A total of 89 patients with egg allergy featuring diarrhoeal symptoms (average age, 23.2 years; range, 1-78 years), all of whom tested positive for egg white-specific IgG, were enrolled in this study. The concentration of total IgE, egg white-specific IgE and number of eosinophils in the serum were determined. RESULTS Among the 89 egg white allergic patients tested, 49 (55.1%) patients showed high reactivity to egg white-specific IgG, 48 (53.9%) patients had elevated serum total IgE levels, and 25 (28.1%) patients had elevated absolute eosinophil numbers. Out of the 89 egg white allergic patients, 25 showed elevated egg white-specific IgE antibody levels. Of the 25 patients who were positive for egg white-specific IgE antibody, 21 presented high sensitive reaction to egg white-specific IgG, three presented moderate sensitive reaction to egg white-specific IgG, and one presented mild sensitive reaction to egg white-specific IgG. A moderate correlation between egg white-specific IgG and egg white-specific IgE, egg white-specific IgG and absolute eosinophil number was found in the egg white allergic patients (r=0.438, P=0.000; r=0.322, P=0.002). Egg white-specific IgE levels varied in different age groups; the egg white-specific IgE concentration of younger patients (age≤18 years, mean rank 54.29) was significantly higher than that of the adult patients (age>18 years, mean rank 34.61) (Z=-3.629, P=0.000). CONCLUSION Egg white-specific IgE antibody could coexist with egg white-specific IgG antibody in patients suffering from egg white allergy. Aberrant changes in the concentration of egg white-specific IgE antibody were associated with the presence of egg white-specific IgG antibody.

Association between neurosyphilis and diabetes mellitus: Resurgence of an old problem 神经梅毒与糖尿病的关系：“旧事”再现: Neurosyphilis and diabetes mellitus

Syphilis, a sexually transmitted disease, is commonly referred to as the “great imitator” because of its wide‐ranging clinical presentations. Recently, we noticed that patients with neurosyphilis (NS) seemed to be more susceptible to complications of diabetes mellitus (DM). This is an interesting phenomenon, but it also puzzles clinicians because of scant knowledge about this situation.