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Xinlong Chen,1 Yanling Gan,2 Dianchang Liu2 1Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, People’s Republic of China; 2Department of STI and Leprosy Prevention and Control, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250022, People’s Republic of ChinaCorrespondence: Dianchang Liu, Tel +86 531-87298850, Email dianchangliu@163.comBackground: Gonorrhea, caused by the bacterium Neisseria gonorrhoeae (NG), is a major public health concern worldwide.Aim of the Study: The aim of this study is to understand the availability of laboratory diagnosis of gonorrhoea in Shandong province and its meaning in case reporting.Methods: Two surveys were conducted among hospitals providing clinical services for sexually transmitted infection (STI) in Shandong Province in 2012 and 2018. The availability of laboratory tests for NG and distribution of reported gonorrhea cases were compared among different hospitals provided clinical services for STI in Shandong province. Descriptive analysis and Chi-square were used for statistical analysis.Results: Smear, culture and PCR tests for NG were used among 301(74.69%), 123(30.52%), 43(10.67%) hospitals in 2012 and 356(74.48%), 176(36.82%) and 73(15.27%) hospitals in 2018, respectively. Significant differences were observed in the availability of smear among hospitals at different levels (X2=12.159, p=0.000) and with different affiliations (X2=4.551, p=0.033) in 2018. Significant differences were observed in the availability of culture and PCR tests among hospitals at different levels both in 2012 (X2=34.532, p=0.000; X2=7.380, p=0.007) and 2018 (X2=49.820, p=0.000; X2=21.658, p=0.000). The availability of culture and PCR tests for NG among hospitals in 2018 was higher than that in 2012 (X2=3.870, p=0.049; X2=4.050, p=0.044). More hospitals reported gonorrhea cases in 2018 than in 2012 (X2=6.768, p=0.009). A significant difference was observed in distribution of case reporting among hospitals at different levels in 2018 (X2=6.975, p=0.008) and among different types of hospital both in 2012 (X2=52.362, p=0.000) and 2018 (X2=74.478, p=0.000).Conclusion: Poor availability of NG laboratory tests affects case reporting, and which is a crucial reason leading to underreporting of gonorrhea cases in Shandong province.Keywords: gonorrhea, availability, laboratory tests, underreporting

The reported prevalence of genital Chlamydia trachomatis infection (GCTI) is much lower in low-income countries than that in high-income countries. This study surveyed the prevalence of GCTI in 456 hospitals in Shandong province, China in December 2018. Among the hospitals surveyed, antigen testing, PCR testing, and either antigen or PCR testing were available in 200 (43.9%), 88 (19.3%), and 268 (58.8%) hospitals, respectively. PCR testing was more available in tertiary hospitals than in primary and secondary hospitals (χ2 = 28.560, P = 0.000). Significant differences were observed in the availability of antigen testing (χ2 = 15.708, P = 0.003), PCR testing (χ2 = 22.494, P = 0.000), and either antigen or PCR testing (χ2 = 21.729, P = 0.000) among different types of hospitals. In 2018, 1532 cases of GCTI were reported in 99 hospitals. Tertiary hospitals reported more cases than those in primary and secondary hospitals (χ2 = 24.082, P = 0.000). The distribution of different types of hospitals that reported GCTI cases was consistent with that of hospitals that provided laboratory testing for GCTI. Antigen and PCR testing were only available in 200 (43.9%) and 88 (19.3%) hospitals, respectively. The results highlighted that the availability of laboratory testing for GCTI in Shandong province was poor, suggesting that the prevalence of GCTI in the province had been sorely underestimated.

Background Estimating prevalence of Chlamydia trachomatis (CT) worldwide is necessary in designing control programs and allocating health resources. We performed a meta-analysis to calculate the prevalence of CT in the general population. Methods The Pubmed and Embase databases were searched for eligible population-based studies from its inception through June 5, 2019. Q test and I2 statistic were used to calculate the heterogeneity between studies. Random effects models were used to pool the prevalence of CT. Meta regression was performed to explore the possible sources of heterogeneity. Publication bias was evaluated using a funnel plot and “trim and fill” method. Results Twenty nine studies that reported prevalence of CT infection from 24 countries were identified, including a total population of 89,886 persons. The pooled prevalence of CT among the general population was 2.9% (95% CI, 2.4–3.5%), and females had a higher CT prevalence (3.1, 95% CI, 2.5–3.8%) than males (2.6, 95% CI, 2.0–3.2%) (χ2 = 10.38, P Conclusions This study provided the updated prevalence of CT among general population worldwide. General population from Latin America, especially females, and women in Africa should be given priority by WHO when design and delivery CT control programs.

The aim of this study was to understand the availability of laboratory testing for syphilis among hospitals in Shandong province. Basic information on hospitals that provide clinical health service for sexually transmitted infections (STIs) and the type of laboratory tests for syphilis provided was collected and analyzed using the chi-square test. A total of 410 and 456 hospitals that provided clinical services for STI were surveyed in 2012 and 2018. Significant differences in the availability of nontreponemal tests were observed among different levels (χ2 = 6.624) and types (χ2 = 17.752) of hospitals in 2012, but not in 2018. A significant difference in the availability of treponemal tests was observed among different levels of hospitals in 2012 (χ2 = 9.937) but not in 2018. Significant differences in the availability of nontreponemal tests, titer of nontreponemal tests, and treponemal tests were observed among hospitals with different affiliations in 2018 ( P = 0.000; χ2 = 15.274, P < .001; P = .021) but not in 2012. The availability of nontreponemal and treponemal tests for syphilis among hospitals in 2018 was higher than that in 2012 (90.13% vs. 57.56%, χ2 = 121.219). The availability of laboratory testing has been much improved. Further efforts are needed to reduce the disparity in the availability among different hospitals.

Background Herpes simplex virus type-2 (HSV-2) infection is the main cause of genital ulcer disease and increases the risk of HIV acquisition. Little information is available regards the epidemiological characteristics of HSV-2 among general population in China. The aim of this study was to explore seroprevalence and associated factors of HSV-2 and provide information for design of HSV-2 control strategy in Shandong, China. Methods In this cross-sectional study, a total of 8074 persons, 18–49 years of age, were selected using multi-stage probability sampling to represent the general population of Shandong in 2016. Demographic data were collected through face-to-face interviews. Other variables were obtained by self-administered questionnaire surveys. Blood was collected for HSV-2 IgG detection with ELISA. Results A total of 7256 sexually-active participants were included in the analysis. The weighted seroprevalence of HSV-2 infection was 4.2% (95% confidence interval [CI], 3.2–5.3) in females, which was significant higher than that in males (2.7%; 95% CI, 1.1–4.2) (P = 0.04). The seroprevalence of HSV-2 was higher in individuals from eastern region (6.4%; 95% CI, 5.9–6.9) and urban areas (4.3%; 95% CI, 2.6–6.0) of Shandong than those from other regions (P

The reported prevalence of genital Chlamydia trachomatis infection (GCTI) is much lower in low-income countries than that in high-income countries. This study surveyed the prevalence of GCTI in 456 hospitals in Shandong province, China in December 2018. Among the hospitals surveyed, antigen testing, PCR testing, and either antigen or PCR testing were available in 200 (43.9%), 88 (19.3%), and 268 (58.8%) hospitals, respectively. PCR testing was more available in tertiary hospitals than in primary and secondary hospitals (χ

Background: Gonorrhea, which is caused by the bacterium Neisseria gonorrhea (NG), is a major public health concern worldwide. The aim of this study is to understand the availability of the laboratory diagnosis of gonorrhea in Shandong Province and its meaning in case reporting. Methods: Two surveys were conducted among hospitals providing clinical services for patients with sexually transmitted infections (STIs) in Shandong Province in 2012 and 2018. The availability of laboratory tests for NG and the distribution of reported gonorrhea cases among different hospitals providing clinical services for patients with STIs in Shandong Province were compared. Descriptive analysis and chi-square test were used for statistical analysis. Results: Smear, culture, and PCR tests for NG were used in 301 (74.69%), 123 (30.52%), and 43 (10.67%) hospitals in 2012 and in 356 (74.48%), 176 (36.82%), and 73 (15.27%) hospitals in 2018. Significant differences were observed in the availability of smear tests among hospitals with different levels (X2 = 12.159, p = 0.000) and with different affiliations (X2 = 4.551, p = 0.033) in 2018. Significant differences were observed in the availability of culture and PCR tests among hospitals at different levels in 2012 (X2 = 34.532, p = 0.000; X2 = 7.380, p = 0.007) and 2018 (X2 = 49.820, p = 0.000; X2 = 21.658, p = 0.000). The availability of culture and PCR tests for NG in hospitals in 2018 was higher than that in 2012 (X2 = 3.870, p = 0.049; X2 = 4.050, p = 0.044). More hospitals reported gonorrhea cases in 2018 than that in 2012 (X2 = 6.768, p = 0.009). A significant difference was observed in the distribution of case reporting among hospitals at different levels in 2018 (X2 = 6.975, p = 0.008) and among different types of hospital in 2012 (X2 = 52.362, p = 0.000) and 2018 (X2 = 74.478, p = 0.000). Conclusions: The poor availability of NG laboratory tests affects case reporting and is a crucial reason that leads to the high sex ratio and under-reporting of gonorrhea cases in Shandong Province.

Background Availability of laboratory testing is the prerequisite for early diagnosis of syphilis. This study aimed to understand the availability of laboratory testing for syphilis among different hospitals in Shandong province. Methods Basic information on hospitals provided clinical health service for sexually transmitted infections in Shandong province and type of laboratory tests for syphilis provided was collected and analyzed using Chi-square test. Results A total of 410 and 456 hospitals provided sexually transmitted infection (STI) clinical services were surveyed in 2012 and 2018, respectively. Significant differences in the availability of nontreponemal tests were observed among hospitals with different levels (X 2 =6.624, p=0.010) and types (X 2 =17.752, p=0.001) in 2012 but not in 2018. A significant difference in the availability of treponemal tests was observed at different levels in 2012 (X 2 =9.937, p=0.002) but not in 2018. Significant differences in the availability of nontreponemal tests, titre of nontreponemal tests, and treponemal tests were observed among hospitals with different affiliations in 2018 (p=0.000; X 2 =15.274, p=0.000; p=0.021) but not in 2012. The availability of both nontreponemal test and treponemal test for syphilis among hospitals in 2018 was higher than that in 2012 (90.13% vs. 57.56%, X 2 =121.219, p=0.000). Conclusions Further efforts are needed to reduce the disparity in availability of laboratory testing for syphilis among different hospitals in China.

Objective Early diagnosis remains the primary goal for leprosy management programs. This study aims to determine whether active surveillance of patients with leprosy and their contact individuals increased identification of latent leprosy cases in the low-endemic areas. Methods This cross-sectional survey was carried out between October 2014 and August 2016 in 21 counties throughout Shandong Province. The survey was conducted among patients with leprosy released from treatment (RFT) and their contacts from both household and neighbors. Results A total of 2,210 RFT patients and 9,742 contacts comprising 7877 household contacts (HHCs), including 5,844 genetic related family members (GRFMs) and 2033 non-genetic related family members and 1,865 contacts living in neighboring houses (neighbor contacts, NCs), were recruited. Among identified individuals, one relapsed and 13 were newly diagnosed, giving a detection rate of 0.12%, corresponding to 120 times the passive case detection rate. Detection rates were similar for HHCs and NCs (0.114% vs. 0.214%, P = 0.287). Analysis of the family history of leprosy patients revealed clustering of newly diagnosed cases and association with residential coordinates of previously-diagnosed multibacillary leprosy cases. Conclusion Active case-finding programs are feasible and contributes to early case detection by tracking HHCs and NCs in low-endemic areas., Author summary Leprosy has been eliminated as a public health problem in 1994 in Shandong Province. However, the district continues to report a relatively high number of cases of leprosy infection involving deformity. Several studies have shown that individuals in contact with people infected with leprosy are at high risk of developing the disease. Subclinical infections among such individuals are important in the chain of M. leprae transmission. Some hyperendemic areas show growing interest in active case finding (ACF). Recent data from the World Health Organization (WHO) show that high rates of relapsed patients, grade 2 disability (G2D) since 2011, and the extensive family history of leprosy among people in Shandong Province P.R. China, indicate a need to reconsider the current approach to leprosy prevention. Active case finding was conducted in 21 counties of Shandong Province among patients with leprosy released from treatment (RFT) and their contacts. We achieved a detection rate of 0.12%, which was much higher than the rate for passive case finding. Our ACF program confirmed the need to implement this strategy among families and neighbors of RFT patients in historically high-endemic areas of leprosy. The program could reduce the risk of G2D by facilitating early detection and treatment, thereby reducing the disease burden.

Few studies have examined the association between methamphetamine (MA) abuse and sexually transmitted infection (STI) risk among heterosexual male MA users in China. A total of 288 heterosexual male MA users who met our inclusion criteria were recruited from nightclubs, KTVs, bars, bath centres and an STI clinic. STIs were screened among the participants, and the risk factors related to STIs were analysed by multivariate logistic regression in SPSS 11.0. Among the 288 heterosexual male MA users, 51 (17.7%) had syphilis, 36 (12.5%) had genital warts, 2 (0.7%) had genital herpes, 3 (1.0%) had HIV infection and 41 (14.2%) had urethritis. STIs were associated with the following variates: ‘MA has the function of anti-inebriation’ (OR = 2.522, 95%CI = 1.337–4.756), ‘I am addicted to MA’ (OR = 4.030, 95%CI = 2.194–7.401), ‘It occurred to me to abstain from MA’ (OR = 2.939, 95%CI = 1.246–6.934), ‘Years of MA abuse’ (OR = 2.622, 95%CI = 1.318–5.215), ‘Times of MA abuse per week’ (OR = 5.275, 95%CI = 1.988–14.002), ‘Number of persons using MA together’ (OR = 2.579, 95%CI = 1.246–5.340) and ‘Number of female sex workers as sex partners per MA abuse’ (OR = 4.004, 95%CI = 1.526–10.508). Our findings show that MA users belong to the high-risk group for STI in China. STIs, except for HIV, have spread widely among heterosexual male MA users. Thus, specific interventions must be conducted to prevent the spread of STIs in this population in China.

Background The shortage of benzathine penicillin G (BPG) worldwide presents a major challenge in the treatment of syphilis. Its availability for syphilis treatment has not been adequately evaluated in China. Methods Two surveys were conducted among hospitals providing sexually transmitted infection clinical services in Shandong Province in 2012 and 2018. Data on the basic information and BPG availability of the surveyed hospitals and related factors were collected and analyzed using SPSS 17.0. Results A total of 433 and 515 hospitals were surveyed in 2012 and 2018, respectively. A significant difference in BPG availability was observed among different levels and types of hospitals both in 2012 (X2 = 9.747, p = 0.008; X2 = 37.167, p = 0.000) and 2018 (X2 = 11.775, p = 0.003; X2 = 28.331, p = 0.000). The BPG availability among surveyed hospitals increased from 45.0% in 2012 to 56.4% in 2018 (X2 = 11.131, p = 0.001). The BPG availability was higher in 2018 than in 2012 among county-level hospitals (52.0% vs. 40.8%, X2 = 7.783, p = 0.005), general western medicine hospitals (62.1% vs. 50.0%, X2 = 6.742, p = 0.009), maternal and child health hospitals (57.1% vs. 26.9%, X2 = 13.906, p = 0.000), and public hospitals (56.8% vs. 45.0%, X2 = 11.361, p = 0.001). However, the county-level availability of BPG (at least one hospital has BPG in a county-level unit) has not improved between 2012 and 2018 (65.93% vs. 70.34%; X2 = 0.563, p = 0.453). The absences of clinical needs, restriction of clinical antibacterial drugs, and lack of qualifications for providing syphilis treatment were the major reasons for the low BPG availability of hospitals. Conclusions BPG availability for syphilis treatment in Shandong Province remains low and presents disparities among different levels and types of hospitals, although it has been improved in recent years. The low availability of BPG for syphilis treatment in China is related to its clinical use by doctors rather than the market supply. Health care reforms should further improve the availability and accessibility of health services. Electronic supplementary material The online version of this article (10.1186/s12913-019-4006-4) contains supplementary material, which is available to authorized users.

Questionnaire on availability of benzathine penicillin G in medical institutions. (DOCX 13 kb)

Background A population-based study of Chlamydia trachomatis (CT) infections is essential in designing a specific control program; however, no large investigation of CT infections among the general population in mainland China has been conducted since 2000. We aimed to determine the prevalence, risk factors, and associated medical costs of CT among residents, 18–49 years of age, in Shandong, China. Methods From May to August 2016, a multistage probability sampling survey involving 8074 individuals was distributed. Data were collected via face-to-face interviews, followed by self-administered questionnaire surveys. First-void urines were collected and tested for CT and Neisseria gonorrhoeae (NG) using nucleic acid amplification. Results The weighted prevalence of CT infection was 2.3% (95% confidence interval [CI], 1.5–3.2) in females and 2.7% (1.6–3.8) in males. Women, 30–34 years of age, had the highest prevalence of CT infections (3.5%, 2.6–4.4), while the highest prevalence of CT infections in males was in those 18–24 years of age (4.3%, 0.0–8.8). Neisseria gonorrhoeae infection had a prevalence of 0.1% (0.0–0.3) in women and 0.03% (0.0–0.1) in men. Risk factors for CT infections among females included being unmarried, divorced, or widowed (odds ratio [OR], 95% CI 3.57, 1.54–8.24) and having two or more lifetime sex partners (3.72, 1.14–12.16). Among males, first intercourse before 20 years of age (1.83, 1.10–3.02) and having two or more lifetime sex partners (1.85, 1.14–3.02) were associated with CT infections. The estimated lifetime cost of CT infections in patients 18–49 years of age in Shandong was 273 million (range, 172–374 million) China Renminbi in 2016. Conclusions This study demonstrated a high burden of CT infections among females

Genome wide association studies (GWASs) have revealed multiple genetic variants associated with leprosy in the Chinese population. The aim of our study was to utilize the genetic variants to construct a risk prediction model through a weighted genetic risk score (GRS) in a Chinese set and to further assess the performance of the model in identifying higher-risk contact individuals in an independent set. The highest prediction accuracy, with an area under the curve (AUC) of 0.743 (95% confidence interval (CI): 0.729–0.757), was achieved with a GRS encompassing 25 GWAS variants in a discovery set that included 2,144 people affected by leprosy and 2,671 controls. Individuals in the high-risk group, based on genetic factors (GRS > 28.06), have a 24.65 higher odds ratio (OR) for developing leprosy relative to those in the low-risk group (GRS≤18.17). The model was then applied to a validation set consisting of 1,385 people affected by leprosy and 7,541 individuals in contact with leprosy, which yielded a discriminatory ability with an AUC of 0.707 (95% CI: 0.691–0.723). When a GRS cut-off value of 22.38 was selected with the optimal sensitivity and specificity, it was found that 39.31% of high risk contact individuals should be screened in order to detect leprosy in 64.9% of those people affected by leprosy. In summary, we developed and validated a risk model for the prediction of leprosy that showed good discrimination capabilities, which may help physicians in the identification of patients coming into contact with leprosy and are at a higher-risk of developing this condition., Author summary Despite elimination efforts, the reported number of new leprosy patients has been relatively stable during the past decade throughout the world. Solid evidence exists that individuals living in close proximity to patients are at an increased risk of developing leprosy, thus identifying the contact individuals who are at a higher risk of developing leprosy is an important aspect of disease control. In the last decade, genome-wide association studies (GWASs) have identified multiple genetic variants associated with leprosy in the Chinese population, however, the combined impact of these variants for leprosy risk prediction remains unclear. The goal of our study was to utilize the genetic variants to construct a risk prediction model in a Chinese set, and further assess the performance of the model in identifying higher-risk contact subjects in an independent set. We developed risk prediction models for leprosy based on GRS encompassing 25 GWAS-derived variants with good discriminatory capability (AUC = 0.743). When compared to the individuals in the high-risk group (GRS > 28.06) and low-risk group (GRS≤18.17), the former had a 24.65 times higher risk for developing leprosy than the latter, which demonstrated a considerable value for risk stratification in leprosy. Our results may assist physicians to identify higher-risk leprosy contact subjects for disease interventions.

The epidemiology of syphilis among older adults in China has not been well studied. We studied changes over time in the prevalence of syphilis among older adults in Shandong, China to inform a syphilis intervention program in order to develop management strategies. We retrospectively reviewed passive surveillance data of syphilis among older adults in Shandong, China during 2008-2013, reported by clinicians in medical facilities. The data included the stage of syphilis, age of patient and gender by year. The prevalences for first, second, latent and overall syphilis by age among adults aged ≥60 years in Shandong were 0.92, 0.70, 2.37 and 3.92 cases per 100,000 population in 2008 and 2.66, 1.99, 9.11 and 13.95 cases per 100,000 population in 2013; giving average yearly increases of 23.66%, 23.24%, 30.90% and 28.90%, respectively. The reported overall prevalence of syphilis among those aged ≥80 years was greater than the general population (8.25 vs 4.38 cases per 100,000 population in 2008; 21.99 vs 13.95 cases per 100,000 population in 2013). The prevalence of syphilis is increasing in the study population. Age appropriate interventions are needed to reduce the prevalence of syphilis in the study population.

Background In China, the mode of HIV transmission and the types and routes of drug use have changed in the past decade. HIV testing amongst drug users needs further improvement. Methods Interviewer-administered questionnaires were used for data collection amongst 600 heterosexual drug users from the community and a municipal detention centre, where criminal suspects are supervised. Descriptive statistics, univariate analysis and multilevel logistic regression analysis were used to identify the factors associated with HIV testing amongst heterosexual drug users. All participants were screened HIV and sexually transmitted infections. Results Amongst 600 participants, 554 (92.3%) were methamphetamine users, and 155 (25.8%) underwent HIV testing in the past year. Multivariate analysis results revealed that drug users who were single (adjusted odds ratio(AOR) = 1.923, 95% confidence interval(CI) = 1.189-3.109), had less knowledge of HIV (AOR = 1.706, 95% CI = 1.074-2.711), used only one kind of drug (AOR = 2.649, 95% CI = 1.155-6.077), used drug via a non-injection route (AOR = 2.121, 95% CI = 1.103-4.078), did not receive free condoms (AOR = 2.307, 95% CI = 1.129-4.715) and who did not receive free publicity material from health workers in the past year (AOR = 2.828, 95% CI = 1.757-4.552) were less likely to undergo HIV testing. A total of 594 participants underwent HIV and syphilis screening in this survey. Amongst these participants, 2 (0.3%) were HIV antibody positive, and 88 (14.8%) showed positive results in both non-treponemal test (rapid plasma regain test) and treponemal test (Treponema pallidum particle agglutination test) for the first time. Conclusions The rate of HIV test uptake amongst heterosexual drug users in China remains low. Thus, more specific interventions are urgently needed to improve the utilisation of HIV testing amongst heterosexual drug users, particularly amongst non-injection drug users in China.

Background: Penicillin is still an essential antibiotic for the treatment and prevention of syphilis. The shortage of benzathine penicillin G (BPG) worldwide presents a major challenge in the penicillin treatment of syphilis. Its availability for syphilis treatment has not been adequately evaluated in China. Methods: Two surveys were conducted among hospitals providing sexually transmitted infection clinical services in Shandong Province in 2012 and 2018. Data on the basic information and BPG availability of the surveyed hospitals and related factors were collected and analyzed using SPSS 17·0. Findings: A total of 433 and 515 hospitals were surveyed in 2012 and 2018, respectively. A significant difference in BPG availability was observed among different levels and types of hospitals both in 2012 (X2=9·747, p=0·008; X2= 37·167, p=0·000) and 2018 (X2=11·775, p=0·003; X2= 28·331, p=0·000). The BPG availability among surveyed hospitals increased from 45·0% in 2012 to 56·4% in 2018 (X2=11·131, p=0·001). The BPG availability was higher in 2018 than in 2012 among county-level hospitals (52·0% vs. 40·8%, X2=7·783, p=0·005), general western medicine hospitals (62·1% vs. 50·0%, X2=6·742, p=0·009), maternal and child health hospitals (57·1% vs. 26·9%, X2=13·906, p=0·000), and public hospitals (56·8% vs. 45·0%, X2=11·361, p=0·001). However, the county-level availability of BPG (at least one hospital has BPG in a county-level unit) has not improved between 2012 and 2018 (65·93% vs. 70·34%; X2=0·563, p=0·453). The absences of clinical needs, restriction of clinical antibacterial drugs, and lack of qualifications for providing syphilis treatment were the major reasons for the low BPG availability of hospitals. Interpretation: The BPG availability for syphilis treatment in Shandong Province has been improved in recent years, although it remains low and presents disparities among different levels and types of hospitals. Its low availability for syphilis treatment in China is related to its clinical use by doctors rather than its market supply. Health care reforms should further improve availability and accessibility of health services. Funding: Shandong Provincial Key R&D Plan. Declaration of Interest: We declare no competing interests.

Estimation process for medical cost of CT infection. (DOCX 20Â kb)

Estimation process for medical cost of CT infection. (DOCX 20Â kb)

Sample size calculation process. (DOCX 12Â kb)

Genome-wide association studies (GWAS) have led to the discovery of several susceptibility loci for leprosy with robust evidence, providing biological insight into the role of host genetic factors in mycobacterial infection. However, the identified loci only partially explain disease heritability, and additional genetic risk factors remain to be discovered. We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls. Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicated BATF3, CCDC88B and CIITA-SOCS1 as new susceptibility genes for leprosy. A systematic evaluation of pleiotropic effects demonstrated a high tendency for leprosy susceptibility loci to show association with autoimmunity and inflammatory diseases. Further analysis suggests that molecular sensing of infection might have a similar pathogenic role across these diseases, whereas immune responses have discordant roles in infectious and inflammatory diseases.

Background A few new leprosy cases still can be seen in Shandong province after elimination. In post-elimination era, government commitments dwindled and active case-finding activities were seldom done. Most of the cases were detected by passive modes and advanced cases with longer delay and visible disability were common. Materials and methods Comprehensive measures including health promotion, personnel training, reward-offering, symptom surveillance and a powerful referral center were implemented in the past decade. The diagnosis of leprosy was mainly based on three cardinal clinical signs. Two-group classification system developed by the WHO was used and cases were classified into multibacillary (MB) type or paucibacillary (PB) type. Cases detected during period 2007–2017 were analyzed and associated factors of grade 2 disability (G2D) were explored. Results 231 new leprosy cases detected during 2007–2017 were analyzed. The mean age at diagnosis is 51.7±16.0 years and the number of males, peasants, illiterates, MB cases, G2D cases and immigrants were 130(56.3%), 221(95.7%), 73(31.6%), 184(79.7%), 92(39.8%) and 40(17.3%) respectively. 181(78.4%) cases were reported by skin clinics and 152 (65.8%) cases came from formerly high endemic counties/districts. The annual number of new cases showed a decreasing trend, from 42 cases in 2008 to 13 cases in 2017. 92 (39.8%) cases presented with G2D at diagnosis. The annual proportion of new cases with G2D declined from 50% in 2008 to 23% in 2017. PB type (OR = 2.76, 95% CI, 1.43–5.32), >12 months of patient delay (OR = 2.40, 95% CI, 1.38–4.19), >24 months of total delay (OR = 4.35, 95% CI, 2.33–8.11), detected by non skin-clinic (OR = 3.21, 95% CI, 1.68–6.14), known infectious source (OR = 1.77, 95% CI, 1.01–3.12) were associated with G2D. Conclusion A few scattered cases still can be seen in post-elimination era and some kind of leprosy control program is still necessary. Government commitments including adequate financial security and strong policy support are vital. Comprehensive case-finding measures including health promotion, personnel training, reward-offering, with an emphasis on former high or middle endemic areas, are necessary to improve early presentation of suspected cases and to increase suspicion and encourage participation of all relevant medical staff. Symptom surveillance based on a powerful transfer center may play an important role in the early detection of new cases in post-elimination era., Author summary After elimination, most of the leprosy cases were detected passively and advanced cases with longer delay and visible disability were common. In the past decade, comprehensive case-finding measures including health promotion, personnel training, reward-offering symptom surveillance and a powerful referral center were implemented successively in Shandong province after the restoration of government commitments. 231 cases detected during 2007–2017 were analyzed and factors associated with G2D were explored. Annual proportion of G2D among new cases showed a declining trend, from 50% in 2008 to 23% in 2017. PB type, longer delay in diagnosis, detected by other than skin-clinics and known infectious sources were associated with G2D. Even in late phase of leprosy control, some kind of leprosy control program is still necessary. Comprehensive case-finding measures based on government commitments would be beneficial to improve early detection of leprosy cases.

Doxycycline is the preferred recommended second-line treatment for the treatment of early syphilis. Recent reports showed a declining efficacy trend of doxycycline in treatment of early syphilis. The aim of our study was to assess the serological response to the treatment for early syphilis with doxycycline compared with benzathine penicillin G and evaluate whether doxycycline is still an effective agent for the treatment of early syphilis. A record-based retrospective study was conducted. Patients were diagnosed with early syphilis in an sexually transmitted disease (STD) clinic from January 1, 2008 to December 31, 2014. They were treated with a single dose of benzathine penicillin G 2.4MU or oral doxycycline 100 mg twice daily for 14 days. Pearson’s chi-squared test was used for data analysis. 601 cases were included in the final study sample: 105 (17.5%) patients received a 14-day course of doxycycline (doxycycline group), and 496 (82.5%) patients received single-dose benzathine penicillin G (BPG group). The serological responses at 6 months and 12 months after treatment were compared. No statistically significant differences were found between the two groups at 6 months (69.52% vs. 75.00%, P=0.245), and at 12 months (92.38% vs. 96.17%, P=0.115). Doxycycline is still an effective agent for the treatment of early syphilis.

Of eight leprosy susceptibility loci identified by genome-wide association studies, five have been implicated in Crohn disease, suggesting a common genetic fingerprint between leprosy and inflammatory bowel disease (IBD). Here, we conducted a multiple-stage genetic association study of 133 IBD susceptibility loci in multiple leprosy samples (totaling 4,971 leprosy cases and 5,503 controls) from a Chinese population and discovered two associations at rs2058660 on 2q12.1 (p = 4.57 × 10(-19); odds ratio [OR] = 1.30) and rs6871626 on 5q33.3 (p = 3.95 × 10(-18); OR = 0.75), implicating IL18RAP/IL18R1 and IL12B as susceptibility genes for leprosy. Our study reveals the important role of IL12/IL18-mediated transcriptional regulation of IFN-γ production in leprosy, and together with previous findings, it demonstrates the shared genetic susceptibility between infectious and inflammatory diseases.

We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10(-14), OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10(-11), OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.

After the leprosy control programme in Shandong Province, China, had declared elimination in 1994, it was no longer cost effective to rely on rapid surveys, population surveys and contact tracing for case detection, and since then most new cases have been diagnosed by the dermatological services. The dermatological services will continue to play an important role in diagnosis of the few incident leprosy cases scattered in wide geographic areas and in a population of 90 million. In order to better understand the knowledge and skills in early diagnosis of leprosy among doctors working in dermatological services around the province, doctors attending the dermatological annual meeting and a dermatological training workshop were assessed on their knowledge and skills in early diagnosis of leprosy and their attitude towards leprosy with a semi-structured questionnaire. The results showed that continuous training was needed for dermatologists from both general hospitals and the leprosy control programme. In particular, the training methods for the skills in nerve examination including palpation of peripheral nerves and nerve function assessment should be improved.

Summary Background Previous studies of drug resistance have shown that mutations in the drug resistance-determining region (DRDR) in the Folp1, RpoB and GyrA genes of Mycobacterium leprae are responsible for resistance to dapsone, rifampin and ofloxacin, respectively. Aim To investigate the prevalence of mutations in genes associated with drug resistance in M. leprae isolates from patients with leprosy in Shandong Province. Methods The DRDR in the FolP1, RpoB and GyrA genes was analysed by direct sequencing of the PCR product from 85 isolates of M. leprae sampled from patients with leprosy in Shandong, China. Results Sequencing results were obtained for FolP1, RpoB and GyrA in 67, 57 and 81 of the 85 samples, with mutation rates of 1.5% (1/67), 8.8% 5/57 and 25.9% (21/81). Three multidrug-resistant samples were found among the new cases: one had a mutation in both Folp1 and RpoB, while the other two had a mutation in both RpoB and GyrA. Conclusions Primary resistance appears to be to either single drugs or combinations of two drugs. The resistance rate to dapsone seems to be low. To our knowledge, this is the first case of multidrug-resistant M. leprae from China.

We read with interest the report by Wu et al. ([1][1]) showing that none of the 211 Treponema pallidum strains examined exhibited 23S rRNA mutations (i.e., A2058G and A2059G) associated with resistance to macrolides. Their finding suggests that azithromycin remains an appropriate alternative

Background Despite the increasing risk of HIV infections, few studies concerning the characteristics of non-injecting heterosexual methamphetamine (MA) users and related risk behaviours have been conducted in China. Methods Gender differences in socio-demographic characteristics, perception of MA and STD/HIV, MA use practices, and sexual behaviours related to MA use were examined among 398 non-injecting heterosexual MA users (288 males, 110 females). Results Male MA users were more likely to be married, local, and self-employed; female MA users were more likely to be young, single, engaged in commercial service or unemployed. Female MA users usually start MA use at an earlier age than males (24.3 vs. 31.3 years old), with shorter abuse durations (2.6 vs. 2.9 years), higher frequency of MA use (3.6 vs. 2.4 times per week), and higher likelihood of using MA with heterosexual partners (100% vs. 78.1%). More male MA users have had multiple sex partners (96.9% vs. 77.3%) and sex exchanges (72.9% vs. 46.4%). Among 277 males who had had sex with commercial sex workers (CSW), 69.4% never used condoms, and among 77 males who had had sex with multiple partners who are commercial sex workers and always or usually used condoms, 87.0% never changed condoms when changing partners. Conclusion There may be gender difference in the characteristics of high-risk behaviours among non-injecting heterosexual MA users. The findings suggest the integration of specific risk reduction strategies into intervention programs for non-injecting heterosexual MA user populations may significantly improve program goals.

Background Human leukocyte antigens (HLAs) have been proposed to modulate the immune response to Mycobacterium leprae. The association of HLA-DRB1 with leprosy has been reported in several populations, but not in a Chinese population. Methods The polymerase chain reaction-sequence-specific oligonucleotide probe with Luminex100 (PCR-SSOP-Luminex) method was used to genotype HLA-DRB1 alleles in 305 leprosy patients and 527 healthy control individuals. Results The HLA-DRB1*15 allele was significantly more prevalent among leprosy patients than healthy controls, whereas the frequency of the HLA-DRB1*09 allele was lower among leprosy patients, especially those with early-onset disease. Conclusion HLA-DRB1 alleles are associated with leprosy susceptibility in a Chinese population. The HLA-DRB1*09 allele was found to be protective exclusively in a subset of early-onset leprosy patients.