Clinical spectrum of late symptomatic neurosyphilis in China: an 11-year retrospective study.

OBJECTIVES: This study aimed to describe the clinical features of neurosyphilis in Chinese patients in an attempt to find clinical features that are helpful for the early identification of neurosyphilis. METHODS: This retrospective study included people with syphilis who visited Shanghai Skin Disease Hospital between January 2010 and December 2020. Lumbar puncture was performed on those who met the inclusion and exclusion criteria. The diagnosis of neurosyphilis was based on clinical and laboratory findings. The parameters were analysed statistically. RESULTS: Of the 3524 patients with neurosyphilis, 2111 (59.9%) and 1413 (40.1%) were asymptomatic and symptomatic neurosyphilis, respectively. General paresis was the most common type of symptomatic neurosyphilis (46.8%). The clinical manifestations of symptomatic neurosyphilis include psychiatric and neurotic symptoms, among which general paresis predominantly presented as psychiatric symptoms such as affective (66.7%) and memory disorder (72.9%). Tabes dorsalis is often presented as neurotic symptoms. One hundred fifty patients (10.6%) with symptomatic neurosyphilis presented candy signs, a rare and specific neurosyphilis symptom that is common in general paresis. Girdle sensation was presented in 13 patients, mainly with tabes dorsalis, which had not been reported in previous studies. CONCLUSIONS: Notably, the candy sign is identified as a specific symptom of general paresis, while girdle sensations are highlighted as a particular symptom of tabes dorsalis. This is the largest study describing the clinical spectrum of neurosyphilis since the onset of the penicillin era and could help doctors learn more about the disease. A comprehensive description of the possible clinical manifestations of late symptomatic neurosyphilis, particularly highlighting rare symptoms, can identify suspicious patients and prevent diagnostic delays.

An observational prospective study based on a large cohort of HIV-negative neurosyphilis patients with particular reference to the Jarisch-Herxheimer reaction.

PURPOSE: The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients. METHODS: A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis. RESULTS: The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5 h after treatment initiation, peaked after 8 h, and subsided after 18 h. Patients with severe JHR experienced a longer recovery time (26 h). Patients with general paresis (OR = 6.825), ocular syphilis (OR = 3.974), pleocytosis (OR = 2.426), or a high CSF-VDRL titre (per log2 titre increase, OR = 2.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided. CONCLUSION: Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy.

Comparison of the efficacy of Hydroquinone cream versus Hydroquinone cream plus Danggui Shaoyao powder in the treatment of melasma.

Introduction: Melasma is an acquired hypermelanosis and occurs in areas exposed to sunlight. Aim: To investigate the effectiveness of Danggui Shaoyao powder (DSP) as a complementary drug in the treatment of melasma. Material and methods: A total of 40 melasma patients over the age of 18 who met the inclusion criteria entered the study randomly in two DSP + Hydroquinone (DSP + H) and Hydroquinone (H) groups. Results: At the beginning of the study, the average MASI score of the two groups of patients had no statistical difference (DSP + H: 15.79 ±1.01 vs. H: 15.37 ±1.17, p = 0.23). But from the eighth week of treatment, the MASI score of the patients decreased significantly and in the DSP + H group it decreased statistically significantly compared to the H group (DSP + H: 5.83 ±0.97 vs. H: 8.29 ±2.23, p < 0.001 for the eighth week and DSP + H: 3.60 ±0.58 vs. H: 5.52 ±1.73, p < 0.001 for the twelfth week of the treatment). It means after 12 weeks of treatment, the average MASI score of patients in the DSP + H group decreased by 77.26 ±2.70%, but in the grroup H, it decreased by 64.31 ±9.68% (p < 0.001). Dynamic PGA showed that excellent treatment occurred in 65% of the + H group H, but only 20% of the H group (p = 0.01). Conclusions: Oral DSP for 12 weeks along with hydroquinone cream can significantly reduce the MASI score of melasma patients and increase the patients' recovery and satisfaction.

Clinicopathologic assessment of secondary syphilis avoids misdiagnosis: results of comprehensive evaluation of 114 cases.

Introduction: Secondary syphilis is well-known for its protean cutaneous manifestations and therefore very easy to be misdiagnosed. Aim: The current study was to observe the frequency of histopathological features characterizing secondary syphilis, and summarize the diseases most likely to be misdiagnosed. Material and methods: In this study a total of 129 pathological specimens from 114 patients with biopsy-proven secondary syphilis were retrospectively analysed and categorized according to clinicopathologic characteristics. The frequency of histopathological features characterizing secondary syphilis were analysed by comparison with clinical features. Results: We found that in a single sample there is at least one feature or at most 13 features exist concurrently, and most demonstrated between 5 and 9 diagnostic features. Plasma cells (97.6% overall vs. 94.0% ≤ 6 features), endothelial swelling (86.8% vs. 74.0%), epidermis hyperplasia (73.6% vs. 62.0%) especially irregular acanthosis, lymphocytes infiltration (71.3% vs. 52.0%) and interstitial patterns (69% vs. 72.0%) were the most common findings in all cases as well as in cases with ≤ 6 features. Granulomatous inflammation is an uncommon histopathologic pattern in secondary syphilis (12.4%). The rash morphologies of our biopsies mainly manifesting as macules and maculopapules were more likely to have 6 or fewer features, which were not only easily misdiagnosed for pityriasis rosea, tinea and erythema multiforme, but also mostly taken from the trunk and genitalia. Atypical morphologies can be combined with plasma cell infiltration and T. pallidum immunohistochemical stain to confirm the diagnosis. Conclusions: In this study plasma cells from superficial and deep perivascular distribution to nodular infiltration were a crucial clue for diagnosis of secondary syphilis.

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.

In this study, we aimed to investigate the performance of nontreponemal antibody tests in cerebrospinal fluid (CSF) specimens from syphilis patients. From September 2009 to September 2012, CSF specimens were collected at the Shanghai Skin Disease Hospital in Shanghai, China, from 1,132 syphilis patients without HIV infection, including 154 with symptomatic and 56 with asymptomatic neurosyphilis. All of the CSF specimens underwent testing with a rapid plasma reagin (RPR) test, an RPR-V (commercial RPR antigen diluted 1:2 in 10% saline) test, the toluidine red unheated serum test (TRUST), and the Venereal Disease Research Laboratory (VDRL) test. Specificities, sensitivities, positive predictive values (PPVs), negative predictive values (NPVs), and kappa values were calculated to determine the performances of the tests. We compared results of the CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST among patients with symptomatic and asymptomatic neurosyphilis who had reactive CSF-Treponema pallidum particle agglutination (TPPA) test results. Overall, the CSF-VDRL test was reactive in 261 patients (23.1%). There were no cases in which the CSF-VDRL was nonreactive and CSF-RPR, CSF-RPR-V, or CSF-TRUST was reactive. Agreement between the results of CSF-TRUST and CSF-RPR was almost perfect (κ=0.861), with substantial agreement between the results of CSF-RPR and CSF-RPR-V (κ=0.740). The sensitivities of CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST were 81.4%, 76.2%, 79.5%, and 76.2%, respectively. Compared to CSF-VDRL, CSF-RPR, CSF-RPR-V, and CSF-TRUST had comparable PPVs and NPVs. However, the specificity of CSF-VDRL (90.3%) was significantly lower than those of the other tests (92.7 to 93.4%). Therefore, CSF-RPR, CSF-RPR-V, and CSF-TRUST can be considered alternative tests for neurosyphilis diagnosis in HIV-negative populations, particularly when the CSF-VDRL is not available.

Partner notification uptake for sexually transmitted infections in China: a systematic literature review.

OBJECTIVE: China's sexually transmitted infection (STI) epidemic requires comprehensive control programmes. Partner services are traditional pillars of STI control but have not been widely implemented in China. This study was a systematic literature review to examine STI partner notification (PN) uptake in China. METHODS: Four English and four Chinese language databases were searched up to March 2011 to identify articles on PN of STIs including HIV in China. PN uptake was defined as the number of partners named, notified, evaluated or diagnosed per index patient. RESULTS: A total of 11 studies met inclusion criteria. For STI (excluding HIV) PN, a median 31.6% (IQR 27.4%-65.8%) of named partners were notified, 88.8% (IQR 88.4%-90.8%) of notified partners were evaluated and 37.9% (IQR 33.1%-43.6%) of evaluated partners were diagnosed. For HIV PN, a median 15.7% (IQR 13.2%-36.5%) of named partners were notified, 86.7% (IQR 72.9%-90.4%) of notified partners were evaluated and 27.6% (IQR 24.1%-27.7%) of evaluated partners were diagnosed. A mean of 80.6% (SD=12.6%) of patients attempted PN, and 72.4% (IQR 63.8%-81.1%) chose self-referral when offered more than one method of PN. Perceived patient barriers included social stigma, fear of relationship breakdown, uncertainty of how to notify and lack of partner contact information. Perceived infrastructure barriers included limited time and trained staff, mistrust of health workers and lack of PN guidelines. CONCLUSION: PN programmes are feasible in China. Further research on STI PN, particularly among men who have sex with men and other high-risk groups, is an important public health priority. PN policies and guidelines are urgently needed in China.

Molecular typing of Treponema pallidum causing early syphilis in China: a cross-sectional study.

BACKGROUND: There have been limited data on molecular epidemiology of syphilis in China. This study aimed to analyze strain type distribution of Treponema pallidum causing early syphilis across geographic areas in China using an enhanced method. METHODS: Genital samples were collected from patients in East, South, and North China. Positive DNA of T. pallidum was analyzed by arp, tpr, and tp0548 genes. RESULTS: Sufficient DNA for full molecular typing existed in 197 of 324 samples, and 27 strain types were identified. A range of 3 to 20 repeats (except 4, 11, and 19 repeats) and 25 repeats were found for the 60-bp tandem repeats of the arp gene. This was the first time the 9 and 25 repeats were detected. For the RFLP analysis of the tpr genes, patterns a, d, h, j, and l were identified. This was the first time the h, j, and l patterns were observed in China. For the sequence analysis of the tp0548 gene, sequences c, e, and f were identified. Strain type distribution was significantly different across geographic areas (χ² = 20.6, P = 0.006). Overall, 14d/f was most predominant (39% of fully typed samples, 95% CI = 32%-46%); 13d/f, 15d/f, and 16d/f were next most common (each 13% of fully typed samples, 95% CI = 9%-18%). CONCLUSIONS: There is substantial genetic diversity of T. pallidum in China. The broad and ununiform distribution of strain types may reflect differences in regional sexual network patterns. Predominance of few strain types may indicate a linked transmission.

PRR11 and SKA2 promote the proliferation, migration and invasion of esophageal carcinoma cells.

Proline-rich protein 11 (PRR11) together with its upstream adjacent gene, spindle and kinetochore associated 2 (SKA2), represent a classic, head-to-head gene pair. The role of the PRR11 and SKA2 gene pair has been described in various types of cancer, including breast cancer, non-small cell lung cancer, hepatocellular carcinoma and ovarian carcinoma. However, its role in esophageal carcinoma (ESCC) remains unclear. The mRNA expression levels of PRR11 and SKA2 were examined in ESCC surgical specimens. In addition, the role of PRR11 and SKA2 in the proliferation and migratory and invasive capacities of EC9706 and EC109 cell lines was examined. The results from the present study demonstrated that PRR11 and SKA2 expression levels were upregulated in ESCC tissues compared with adjacent normal tissues. Furthermore, PRRl1 and SKA2 knockdown significantly inhibited the proliferation and migratory and invasive capacities of ESCC cells. Conversely, PRRl1 and SKA2 overexpression significantly promoted the proliferation and migratory and invasive capacities of ESCC cell lines via activation of the AKT signaling pathway and certain markers of epithelial-mesenchymal transition, including Snail and N-cadherin. The results from the present study suggested that the PRR11 and SKA2 gene pair may represent a potential target in the diagnosis and treatment of ESCC.

The 5.8S pre-rRNA maturation factor, M-phase phosphoprotein 6, is a female fertility factor required for oocyte quality and meiosis.

OBJECTIVES: M-phase phosphoprotein 6 (MPP6) is important for 5.8S pre-rRNA maturation in somatic cells and was screened as a female fertility factor. However, whether MPP6 functions in oocyte meiosis and fertility is not yet known. We aimed to address this. MATERIALS AND METHODS: Mouse oocytes with surrounded nucleus (SN) or non-surrounded nucleus (NSN) were used for all experiments. Peptide nanoparticle-mediated antibody transfection was used to deplete MPP6. Immunofluorescence staining, immunohistochemistry and live tracker staining were used to examine MPP6 localization and characterize phenotypes after control or MPP6 depletion. High-fidelity PCR and fluorescence in situ hybridization (FISH) were used to examine the localization and level of 5.8S rRNAs. Western blot was used to examine the protein level. MPP6-EGFP mRNA microinjection was used to do the rescue. RESULTS: MPP6 was enriched within ovaries and oocytes. MPP6 depletion significantly impeded oocyte meiosis. MPP6 depletion increased 5.8S pre-rRNA. The mRNA levels of MPP6 and 5.8S rRNA decreased within ageing oocytes, and MPP6 mRNA injection partially increased 5.8S rRNA maturation and improved oocyte quality. CONCLUSIONS: MPP6 is required for 5.8S rRNA maturation, meiosis and quality control in mouse oocytes, and MPP6 level might be a marker for oocyte quality.

MiR-216a-5p-containing exosomes suppress rTp17-induced inflammatory response by targeting TLR4.

Syphilis caused by Treponema pallidum (T. pallidum) infection is accompanied by inflammatory injury of tissue, and has a worldwide distribution and increasing incidence over the past decade. Tp17 has been reported to be a strong membrane immunogen, and was initially observed to play a role in inflammation during syphilis, reacting intensely with human syphilitic sera. We therefore used recombinant Tp17 (rTp17) as a stimulator in our study. Increasing evidence has demonstrated that microRNA (miRNA)-containing exosomes have emerged as a potential effective therapeutic target for many diseases. However, the biological functions and molecular mechanisms of miR-216a-5p in syphilis pathogenesis remain unknown. Our study first identified dramatically decreased miR-216a-5p in plasma of syphilis patients compared with the healthy control, which was negatively correlated with the expression of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Moreover, endothelial cells treated with miR-216a-5p-containing exosomes significantly attenuated the rTp17-induced inflammatory response. More importantly, we identified that miR-216a-5p could bind to the 3'-untranslated region (UTR) of Toll-like receptor (TLR) 4 (TLR4), and overexpression of TLR4 largely rescued the miR-216a-5p-mediated suppression of rTp17-induced inflammatory cytokine production and the TLR4-MYD88 signaling pathway. Thus, our results reveal a novel role of miR-216a-5p-containing exosomes in endothelial cells, implying a potential therapeutic target for inflammation in syphilis patients.

Single xenotransplant of rat brown adipose tissue prolonged the ovarian lifespan of aging mice by improving follicle survival.

Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long-acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat-to-mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.

The ubiquitin ligase KBTBD8 regulates PKM1 levels via Erk1/2 and Aurora A to ensure oocyte quality.

Tight control of energy metabolism is essential for normal cell function and organism survival. PKM (pyruvate kinase, muscle) isoforms 1 and 2 originate from alternative splicing of PKM pre-mRNA. They are key enzymes in oxidative phosphorylation and aerobic glycolysis, respectively, and are essential for ATP generation. The PKM1:PKM2 expression ratio changes with development and differentiation, and may also vary under metabolic stress and other conditions. Until now, there have been no reports about the function and regulation of PKM isozymes in oocytes. Here, we demonstrate that PKM1 or PKM2 depletion significantly disrupts ATP levels and mitochondrial integrity, and exacerbates free-radical generation and apoptosis in mouse oocytes. We also show that KBTBD8, a female fertility factor in the KBTBD ubiquitin ligase family, selectively regulates PKM1 levels through a signaling cascade that includes Erk1/2 and Aurora A kinases as intermediates. Finally, using RNA sequencing and protein network analysis, we identify several regulatory proteins that may be govern generation of mature PKM1 mRNA. These results suggest KBTBD8 affects PKM1 levels in oocytes via a KBTBD8→Erk1/2→Aurora A axis, and may also affect other essential processes involved in maintaining oocyte quality.

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

BACKGROUND: Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. METHODOLOGY/PRINCIPAL FINDINGS: Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. CONCLUSIONS/SIGNIFICANCE: Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.

Optimizing Partner Notification Programs for Men Who Have Sex with Men: Factorial Survey Results from South China.

BACKGROUND: Syphilis is prevalent among men who have sex with men (MSM) in China. Syphilis partner notification (PN) programs targeting MSM has been considered as one of effective strategies to prevention and control of the infection in the population. We examined willingness and preferences for PN among MSM to measure feasibility and optimize uptake. METHODS: Participation in a syphilis PN program was measured using a factorial survey from both the perspective of the index patient and the partner. Respondents were recruited from April-July 2011 using convenience sampling at two sites-a MSM sexually transmitted disease (STD) clinic and a MSM community based organization (CBO). Respondents first evaluated three factorial survey vignettes to measure probability of participation and then an anonymous sociodemographic questionnaire. A two-level mixed linear model was fitted for the factorial survey analysis. RESULTS: In 372 respondents with mean age (± SD) 28.5 (± 6.0) years, most were single (82.0%) and closeted gays (66.7%). The Internet was the most frequent place to search for sex. Few (31.2%) had legal names for casual partners, but most had instant messenger (86.5%) and mobile phone numbers (77.7%). The mean probability of participation in a syphilis PN program was 64.5% (± 32.4%) for index patients and 63.7% (± 32.6%) for partners. Referral of the partner to a private clinic or MSM CBO for follow-up decreased participation compared to the local Center for Disease Control and Prevention (CDC) or public STD clinic. CONCLUSIONS: Enhanced PN services may be feasible among MSM in South China. Internet and mobile phone PN may contact partners untraceable by traditional PN. Referral of partners to the local CDC or public STD clinic may maximize PN participation.

Prevalence and genotype distribution of cervical human papillomavirus infection among female sex workers in Asia: a systematic literature review and meta-analysis.

Cervical human papillomavirus (HPV) infection is highly transmissible. Although there are many studies on HPV infection in general population of women globally, little attention has been paid to female sex workers (FSWs) in Asia. In this study, we used a meta-analytic approach to systematically analyse the literature to elucidate the prevalence and genotype distribution of cervical HPV infection among FSWs in Asia. Fourteen eligible studies were identified in five databases, and data including 4198 FSWs from nine Asian countries were aggregated. Crude estimates of cervical HPV prevalence among FSWs in this region ranged from 12.8% to 84.8%. FSWs had a nearly 10-fold risk of HPV infection than the general population of women. Stratified analysis showed that HPV prevalence was higher in East Asia than other subregions and in younger FSWs than older FSWs. HPV genotype distribution was statistically different between East Asia and South-east Asia. In East Asia, the most prevalent genotypes were HPV 16 (23.9%), 18 (11.0%), 58 (9.4%), 56 (6.3%) and 52 (5.3%), while they were HPV 52 (12.9%), 16 (8.5%), 58 (5.2%), 18 (5.0%) and 66 (4.9%) in South-east Asia. HPV 31, 33 and 35 were less frequently found in both subregions. HPV infection was substantial among FSWs in some Asian countries. More studies are necessary to illustrate the overall picture of HPV infection in this region.

HIV incidence among men who have sex with men in China: a meta-analysis of published studies.

BACKGROUND: Men who have sex with men (MSM) have now become one of the priority populations for prevention and control of HIV pandemic in China. Information of HIV incidence among MSM is important to describe the spreading of the infection and predict its trends in this population. We reviewed the published literature on the incidence of HIV infection among MSM in China. METHODS: We identified relevant studies by use of a comprehensive strategy including searches of Medline and two Chinese electronic publication databases from January 2005 to September 2010. Point estimate of random effects incidence with corresponding 95% confidence intervals (CI) of HIV infection was carried out using the Comprehensive Meta-Analysis software. Subgroup analyses were examined separately, stratified by study design and geographic location. RESULTS: Twelve studies were identified, including three cohort studies and nine cross-sectional studies. The subgroup analyses revealed that the sub-overall incidence estimates were 3.5% (95% CI, 1.7%-5.3%) and 6.7% (95% CI, 4.8%-8.6%) for cohort and cross-sectional studies, respectively (difference between the sub-overalls, Q = 5.54, p = 0.02); and 8.3% (95% CI, 6.9%-9.7%) and 4.6% (95% CI, 2.4%-6.9%) for studies in Chongqing and other areas, respectively (difference between the sub-overalls, Q = 7.58, p<0.01). Syphilis infection (RR = 3.33, p<0.001), multiple sex partnerships (RR = 2.81, p<0.001), and unprotected receptive anal intercourse in the past six months (RR = 3.88, p = 0.007) represented significant risk for HIV seroconversion. CONCLUSIONS: Findings from this meta-analysis indicate that HIV incidence is substantial in MSM in China. High incidence of HIV infection and unique patterns of sexual risk behaviors in this population serve as a call for action that should be answered with the innovative social and public health intervention strategies, and development of biological prevention strategies.

Molecular typing of Treponema pallidum: a systematic review and meta-analysis.

BACKGROUND: Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. METHODOLOGY/PRINCIPAL FINDINGS: Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ(2) = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ(2) = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. CONCLUSIONS/SIGNIFICANCE: Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis.