Search

To date, genome‐wide association studies (GWASs) have discovered 35 susceptible loci of leprosy; however, the cumulative effects of these loci can only partially explain the overall risk of leprosy, and the causal variants and genes within these loci remain unknown. Here, we conducted out new GWASs in two independent cohorts of 5007 cases and 4579 controls and then a meta‐analysis in these newly generated and multiple previously published (2277 cases and 3159 controls) datasets were performed. Three novel and 15 previously reported risk loci were identified from these datasets, increasing the known leprosy risk loci of explained genetic heritability from 23.0 to 38.5%. A comprehensive fine‐mapping analysis was conducted, and 19 causal variants and 14 causal genes were identified. Specifically, manual checking of epigenomic information from the Epimap database revealed that the causal variants were mainly located within the immune‐relevant or immune‐specific regulatory elements. Furthermore, by using gene‐set, tissue, and cell‐type enrichment analyses, we highlighted the key roles of immune‐related tissues and cells and implicated the PD‐1 signaling pathways in the pathogenetic mechanism of leprosy. Collectively, our study identified candidate causal variants and elucidated the potential regulatory and coding mechanisms for genes associated with leprosy. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Byline: Dianchang. Liu, Tongsheng. Chu, Shumin. Chen Sir, Since syphilis re-emerged in China in the 1970s, the disease has been spreading widely over the country, with an accelerating speed. [sup][1] [...]

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. [ABSTRACT FROM AUTHOR]

This article discusses two cases of fever, rash, and organ involvement during the treatment of leprosy. The first patient, a 65-year-old man, developed a high fever and a generalized rash after 27 days of treatment. The second patient, a 39-year-old woman, developed a fever and a pruritic rash 21 days after treatment. The symptoms in both cases were initially suspected to be a drug-induced hypersensitivity syndrome (DIHS) caused by the medication dapsone (DDS). The diagnosis of DDS-induced hypersensitivity syndrome was confirmed through an HLA-B*13:01 test. Treatment with corticosteroids led to improvement in both patients. The article emphasizes the importance of timely diagnosis and differential diagnosis in the treatment of leprosy and highlights the value of the HLA-B*13:01 test in preventing DDS syndrome. [Extracted from the article]

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-?B 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. [ABSTRACT FROM AUTHOR]

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 < 0.01). Associated factors for HSV-2 infection among men were being urban residents (adjusted odds ratio [AOR], 2.36; 95% CI, 1.14-4.88), having two or more sex partners in the past year (AOR, 3.22; 95% CI, 1.90-5.43) and having commercial sex (AOR, 1.51; 95% CI, 1.00-2.26). Among females, being divorced or widowed (AOR, 1.79; 95% CI, 1.08-2.97), having a tattoo (AOR, 2.89; 95% CI, 1.07-7.84), and being dissatisfied with the sex activity quality (AOR, 2.12; 95% CI, 1.24-3.63) was associated with HSV-2 infection.Conclusions: This study showed a relatively low burden of HSV-2 in Shandong province, China compared with the seroprevalence reported in many other provinces and countries. HSV-2 control programs in Shandong should focus on eastern, urban and female residents, and pay more attention to individuals with identified associated factors. [ABSTRACT FROM AUTHOR]

The article focuses on the Genome-Wide Association Study of single nucleotide polymorphisms (SNP) of association of PARK2 and PACRG with leprosy in Chinese population. The study found no remarkable association of Chinese population with the risk SNPs within the PARK2 and PACRG leprosy region. It is noted that there may be a suggestive association of SNPs with ethnic heterogeneity of susceptibility to leprosy.

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. [Copyright &y& Elsevier]

Importance: Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone., Objective: To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy., Design, Setting, and Participants: A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events., Exposures: Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT., Main Outcomes and Measures: The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control., Results: Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10-5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status., Conclusions and Relevance: Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

Objectives: To determine the prevalence and the characteristics of neuropathic pain among the people affected by leprosy in China., Methods: People affected by leprosy in four leprosy villages were interviewed about neuropathic pain with an interviewer-administrated questionnaire., Results: In a total of 275 patients with leprosy interviewed, 126 (45.8%) reported having symptoms suggestive of neuropathic pain. The pain was severe in 70 (55.5%) patients, moderate in 49 (38.9%) and mild in 7 (5.6%). Of the 126 patients with leprosy, 109 (86.5%) stated that the pain had some impact on their daily life: mild in 13 (10.3%), moderate in 45 (35.7%) and severe in 51 (40.5%). Sleep disturbance caused by pain was reported in 119 (94.4%) patients with leprosy: mild in 13 (10.3%), moderate in 51 (40.5%) and severe in 55 (43.6%). Ninety-six patients with leprosy (76.2%) reported that they had tried analgesics alone or in combination with steroids for the relief of their pain, of which 78 (81.2%) people reported that the treatment was effective., Conclusions: Neuropathic pain is not uncommon in both MB and PB patients who have completed effective antimicrobial treatment. The effectiveness of analgesics alone or in combination with steroids, in the treatment of neuropathic pain in patients with leprosy, needs to be studied.

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.

Delay in diagnosis of leprosy can increase the risk of nerve function impairments and promote the transmission of the infection in a community. In order to understand the factors associated with the delays in diagnosis of leprosy, a questionnaire-based interview was conducted to collect information on the delays among 88 newly diagnosed leprosy patients. The results showed that delay was common and associated with the high rate of disability in the study population. The total mean delay was 50.18 months (median 36 months). The mean patient delay was 24-4 months (median 9.5 months) and the mean health service delay was 257 months (median 12 months). Patients with leprosy reported a variety of symptoms/signs at an early stage of the disease, particularly numbness and tingling. Ignorance of the illness was reported to be the main reason for the patient's delay. Health seeking actions ranged from 1 to 50 with a mean of 7.2 after becoming aware of the first symptom/sign. The effectiveness of early diagnosis of leprosy through health promotion in the population needs to be validated and continuous training on leprosy among healthcare providers is needed.

The accurate diagnosis of leprosy is important to both individuals and to the community. The diagnosis of leprosy is based on clinical examination. However, the reliability of clinical assessment of sensation in skin lesions and thickness of peripheral nerves on palpation has not been well studied, due to the lack of a gold standard. We report an inter-tester reliability study of the clinical assessment of skin lesions and thickness of ulnar and popliteal nerves in leprosy patients by different staff. For sensory testing of skin lesions, the agreement between the leprologist and leprosy control staff, and between one student and leprosy control staff, was poor (kappa values < 0-4). The agreement between the leprologist and the two students, between the two students, and between the other student and local leprosy control staff were fair (kappa values > 0.4, but < 0-6). For the palpation of ulnar and popliteal nerves, the agreement ranged from 0.36 to 0.52 and from 0.02 to 0.29 in different pairs of testers, respectively. The reliability of clinical diagnostic skills based on both sensory testing of skin lesions with the cotton wool method and palpation of superficial peripheral nerves was unsatisfactory.