Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy.

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 Analysis of Protein-Coding Variants in Leprosy.

Although genome-wide association studies have greatly advanced our understanding of the contribution of common noncoding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in Han Chinese, of whom were 7,048 leprosy patients and 14,398 were healthy control subjects. Seven coding variants of exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD (P = 1.71 × 10-9, odds ratio [OR] = 4.35) and rs149308743 in CARD9 (P = 2.09 × 10-8, OR = 4.75); three low-frequency variants: rs76418789 in IL23R (P = 1.03 × 10-10, OR = 1.36), rs146466242 in FLG (P = 3.39 × 10-12, OR = 1.45), and rs55882956 in TYK2 (P = 1.04 × 10-6, OR = 1.30); and two common variants: rs780668 in SLC29A3 (P = 2.17 × 10-9, OR = 1.14) and rs181206 in IL27 (P = 1.08 × 10-7, OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, showed involvement of skin barrier and endocytosis/phagocytosis/autophagy, in addition to known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein-coding variant studies for complex diseases.

Survey on child leprosy patients and problems resulted from the disease in China.

OBJECTIVES: To understand the situation of child leprosy patients in the low prevalence situation pertaining in China. METHOD: A retrospective survey by questionnaire was carried out in all 32 provinces of mainland of China in 2011. All data concerning child cases detected from January 2005 to December 2009 were collected by professional health workers working at county level. RESULTS: During the study, only 165 questionnaires were collected for analysis. Among 165 child cases, 96 were boys, 69 were girls with an average age of 11-7 years old. 80% of child cases were members of families with other leprosy affected people. 145 (85%) child cases took their MDT secretly (nobody outside the family knew the child suffered from leprosy), and three (1.8%) children died, one each from dapsone syndrome, suicide and severe pneumonia. During follow-up, four child cases developed new disability increasing the Grade 2 disability rate to 13.3% (22/165). At end of the study, 8.2% of children had discontinued their study at school, and 7.5% had moved to a remote place to do casual work, while 6.3% stayed at home. 31% of child patients thought that leprosy caused a negative impact on their daily life. Two children had a hostile attitude toward society due to the stigma caused by leprosy. CONCLUSIONS: In both high and low endemic areas, as long as there is an infectious source of leprosy in the family, there is a possibility for children to develop leprosy. Contact surveys should be done to detect early disease, especially when there are children in the household.

Six years' follow-up of multibacillary leprosy patients treated with uniform multi-drug therapy in China.

OBJECTIVE: This study was conducted to evaluate the effectiveness of uniform multi-drug therapy (UMDT) in patients with multibacillary (MB) leprosy. METHODS: Newly detected MB leprosy patients were treated with six months of UMDT as recommended by the World Health Organization (WHO). The effectiveness of treatment was evaluated by clinical status and skin smear tests. RESULTS: At the start, 114 patients were recruited, examined, and treated. These patients were re-examined and followed annually for up to six years. A total of 75 (65.8%) patients completed six years of follow-up. Dropouts were attributable to death, severe drug reactions, and other reasons. The mean ± standard deviation bacteriological index (BI) of all patients decreased from 3.01 ± 1.50 before treatment to 0.02 ± 1.84 at the end of year 6, reflecting a mean annual decrease of 0.50. The rate of smear negativity in all patients was 98.7% at the end of year 6 of follow-up. A total of 53 leprosy reactions were observed. One patient relapsed 13 months after the cessation of treatment. CONCLUSIONS: A 6-month administration of UMDT is effective in MB leprosy patients. The changes in BI values and the frequency of leprosy reactions were similar to those cited in reports in the literature of patients treated with 1- or 2-year regimens of MDT. However, further research should be conducted to confirm the present results.

Dental health and treatment needs in people with leprosy in China.

OBJECTIVES: To evaluate the dental health status and treatment needs of people affected by leprosy in China, and provide a basis for the development of national or regional dental health programmes to cover the treatment needs of this population. DESIGN: A cross-sectional study with 613 former leprosy patients was carried out in six leprosy villages, in three provinces in China (Nanjing, Taixing and Jiangyan in Jiangsu Province, Hanzhong and Shangluo in Shanxi Province and Yongzhou in Hunan Province). A questionnaire about demographic and clinical data was used. The World Health Organization's (WHO) basic methods were used to determine the tooth-based treatment needs. Periodontal status was determined by using the Community Periodontal Index of Treatment Needs (CPITN). In addition, prosthetic normative needs were assessed. RESULTS: Among the 613 people affected by leprosy, there were 472 people (77%) who had never visited a dentist and 172 people (28.1%) had never brushed their teeth; 302 (49.3%) brushed their teeth once a day. However, there were 267 people (43.6%) who thought their dental health was at an average level and 108 (17.6%) thought they had good dental health. 55.6% of the subjects required dental fillings, 32.7% required pulp care and restoration, and 71.1% required extraction. On CPITN, 23.2% of the subjects scored 2, 28.6% scored three and 48.0% scored four, showing that these people required systematic periodontal treatment. In addition, 84.5% of the subjects needed normative prosthetic treatment. CONCLUSIONS: Most of the subjects with leprosy in this study lacked self-care knowledge on dental health, and especially self-awareness of dental conditions. Normative treatment needs of people affected by leprosy were very high. This result calls for improved oral health education and oral health care in people with leprosy. Oral health education might preferably be integrated into already existing leprosy rehabilitation programs.

Dapsone hypersensitivity syndrome among leprosy patients in China.

OBJECTIVE: To Study the incidence and clinical characteristics of dapsone hypersensitivity syndrome (DHS) among MDT-treated leprosy patients from 2006 to 2009 in China. METHODS: A retrospective survey was carried out throughout China using a specially designed questionnaire. RESULTS: From 2006 to 2009, there were 63 new patients reported to have DHS with an incidence of 1.0%. Among these patients, 13 were complete types of DHS, the others were incomplete ones. The average age of patients with DHS was 38 years and the male to female ratio was 2.15. The average incubation period from taking dapsone to DHS onset was 32.8 days (2-6 weeks). There were 60 (95.2%) patients who presented with various skin lesions, 56 (88.9%) with fever, 40 (63.5%) with hepatic damage and 22 (34.9%) with lymphopathy. Seven patients died with a death rate of 11.1% among all patients with DHS. CONCLUSIONS: DHS is a serious adverse event resulted from dapsone. It can occur in a small number of new leprosy patients treated with dapsone containing regimen. Some patients may die of DHS if not taking timely and adequate management. Therefore local doctors should pay an attention to DHS among leprosy patients newly treated with the dapsone-containing MDT regimen.

[Epidemiological analysis on leprosy in China, 2009].

OBJECTIVE: To study the epidemiological characteristics of leprosy and to provide evidence for specific strategies development on leprosy control. METHODS: Descriptive analysis of data from the national leprosy surveillance system was carried out in 2009. RESULTS: A total number of 1597 new cases were detected in 2009 with a case detection rate of 0.120 per 100 000 population. The proportions of children under 15, multibacillary and disability grade 2 were 2.4%, 84.3% and 22.8% respectively. A total number of 148 relapse cases were reported in 2009, among which 69 cases were those relapsed after multi-drug therapy. The existing cases were 6603 by the end of 2009 with a prevalence rate of 0.049 per 10 000 populations, among which 3332 cases were on multi-drug therapy. CONCLUSION: The overall leprosy situation is considered to be at low endemic in China but the distribution is unequal, with pocket areas in Yunnan, Sichuan and Guizhou. In order to reach the target on leprosy elimination, which was considered as a public health and social problem, the input and efforts are needed for many years to come.

A big challenge in case finding at low endemic situation: analysis on 1462 new leprosy patients detected in China in 2007.

OBJECTIVE: To understand the characteristics of newly detected leprosy patients at low endemic situation in China in order to provide information for better leprosy control. METHODS: A study was carried out using a designed questionnaire in a retrospective method in China in 2007. RESULTS: Among 1462 new patients studied, the average age at diagnosis was 41.5 +/- 15.8 years. Nearly half of new patients were detected by a passive method at the skin clinic. This might relate to a long delay between disease onset and diagnosis (3.23 +/- 45 years) as well as a high rate of disability Grade 2 among new patients (22.6%). There were 363 (24.8%) patients who came from non-leprosy endemic areas, 844 (57.7%) patients who came from non-leprosy families and 409 (28.0%) patients who came from villages where leprosy outbreaks had never occurred before. CONCLUSION: Case finding within low endemic areas of China is a big challenge in leprosy control. Maintaining sustainable leprosy control and strengthening leprosy training among dermatologists may be the important strategy in the future.

[A long-term evolution on the epidemiological characteristics of leprosy, towards the goal of its elimination in 1949 - 2007 in China].

OBJECTIVE: To understand the epidemiological characteristics of leprosy during the evolution of the disease, towards the goal of elimination for the past 50 years and longer, so as to provide experiences for accelerating eradication of leprosy in China. METHODS: Data were collected from National Surveillance System of Leprosy which was composed annually of all the data from county-based leprosy unit reporting system. All the data were reviewed retrospectively. RESULTS: A total number of 487 900 leprosy patients were reported from 1949 to 2007 in China. The case detection rate reduced from the highest of 5.56/100 000 in 1958 to the lowest of 0.12/100 000 in 2007. Leprosy patients mainly distributed in mountain areas in Yunnan, Guizhou, Sichuan, Guangdong Guangxi, Hunan and Jiangxi provinces with warm and damp climate and underdeveloped economy. After more than 50 years of leprosy control efforts, the case detection rate declined quickly in provinces in the eastern and the southern parts but very slowly in provinces in the western and the southwestern part of China. The ratio of relapsed patients to newly detected ones increased from 1:139 in 1960s' to 1:10 after 1980s', annually. The proportion of child cases among newly detected patients had been 3% - 4% since 1968. In the recent 20 years, the proportion of new patients with positive skin smear gradually increased and the rate of disability grade two reached 20% and more. The average age of new patients upon diagnosis was 45 years old in the east coastal provinces but only 38 years old in the southwest provinces. A new finding was that some new patients detected in the east coastal provinces were immigrants from the southwestern provinces. CONCLUSION: With continuous socio-economic development and active efforts on leprosy control, the prevalence of leprosy gradually declined despite the long evolution period. Some negative events seemed to have influenced the trend of case detection.

[Long-term results of two temporalis muscle transfer procedures in correction of paralytic lagophthalmos].

OBJECTIVE: To compare the long-term results and possible complications of a modified temporalis muscle transfer (TMT) with the Johnson's procedure in correction of paralytic lagophthalmos. METHODS: From September 1997 to March 2000, paralytic lagophthalmos due to leprosy in 92 patients were corrected with TMT. The 89 cases (127 to eyes including 51 unilateral and 38 bilateral) followed up 3 years after operation were analyzed. There were 69 males and 20 females with ages ranging from 18 to 65 years (52 years on average). The duration of lagophthalmos was 1-22 years with an average of 8.2 years. And 36 eyes were complicated with lower eyelid ectropion. Sixty-five eyes were corrected with Johnson's procedure (Johnson's TMT group), 62 with the modified TMT procedure (modified TMT group). The modifications were as follows: (1) omitting the fascial strip in the lower eyelid to avoid postoperative ectropion. (2) fixing the fascial strip of the upper eyelid to the middle or inner margin of the tarsal palate depending on the degree of the lagophthalmos to avoid possible ptosis of the upper eyelid. RESULTS: In Johnson's TMT group, the mean lid gap on light closure was reduced to 3.1 mm postoperatively from 7.7 mm preoperatively; and the mean lid gap on tight closure was reduced to 0.5 mm postoperatively from 6.1 mm preoperatively. The symptoms of redness (73.7%) and tearing (63.7%) disappeared or were improved postoperatively. However, ectropion and ptosis occurred in 24 eyes and 9 eyes respectively. The overall excellent and good rate was 58.5%. In the modified TMT group, the mean lid gap on light closure was reduced to 3.3 mm postoperatively from 7.5 mm preoperatively; and the mean lid gap on tight closure was reduced to 0. 6 mm postoperatively from 6. 3 mm preoperatively. The symptoms of redness (90.9%) and tearing (71.0%) disappeared or were improved postoperatively, and no ectropion or ptosis was found except one ectropion. The overall excellent and good rate was 87.1%, which was significantly higher than that of Johnson's group (P < 0.01). CONCLUSION: The modified TMT is an efficiency and simple procedure with very few complications, and thus is strongly recommended for use when TMT is an indication.

[Long-term results after the correction of the paralytic ectropion caused with leprosy in 115 eyes].

OBJECTIVE: To analyze the long-term results after the correction of the paralytic ectropion in leprosy. METHODS: Seventy-four patients with 115 paralytic ectropion eyes after leprosy were treated with the surgical procedures included medial canthoplasty, medial canthal tendon plication, lateral tarsal strip, medial canthal resection, lateral canthoplasty, and lid shortening. The results were evaluated with the follow-ups from 2 to 4 years. RESULTS: The eye-redness was reduced from 93 to 40 while the epiphora from 107 eyes (24 mild, 36 moderate and 47 severe) to 90 (40 mild, 32 moderate and 18 severe). The mean lid gap in mild eye closure was reduced from 6.8 mm to 5.3 mm and the cornea lesion was reduced from 53 to 36. The results were excellent in 18 eyes (15.7%), good in 45 eyes (39.1%), fair in 41 eyes (35.7%) and poor in 11 eyes (9.6%). However, the mean visual acuity remained same pre- and postoperatively. CONCLUSIONS: Surgical correction of ectropion is helpful for cornea protection and could improve the signs and symptoms of the eyes such as epiphora and red [abstract truncated].

Comprehensive treatment of complicated plantar ulcers in leprosy.

OBJECTIVE: To investigate feasible treatment methods for plantar ulcers in leprosy patients according to the agreement between the Ministry of Health (MOH) of China and the Leprosy Mission International (LMI). METHODS: A total of 2599 complicated foot ulcers in 1804 leprosy cases underwent surgic treatment. Plastic fixation and supports were used, dressings were changed regularly, and protective footwear and modified insoles were provided. RESULTS: Of the 2599 foot ulcers 1446 (55.64%) healed. The cure rate of the patients treated in leprosy hospitals was 71.31%, with 219 (15.15%) recurrences of foot ulcers. The recurrence rate of those who lived at home was 18.35%. CONCLUSIONS: Comprehensive treatment of foot ulcers has a high cure rate and a low recurrence rate. Reduction of workload, avoidance of long distance walking, intensification of education on foot self-care and provision of financial support are the main measures for preventing a recurrence of foot ulcers.

A survey of blindness and poor vision in leprosy patients.

OBJECTIVE: To determine the prevalence, cause and distributions of blindness and poor vision in patients with leprosy. METHODS: An epidemiological survey of blindness and poor vision among 1045 cases of leprosy was carried out in Taixing City of Jiangsu Province, China. RESULTS: The prevalence of bilateral blindness was 7.67%, unilateral blindness 4.4%, bilateral poor vision of various degrees 9.28% and unilateral poor vision 5.84%. The prevalence of eye complications varied significantly among different groups of patients; females had a higher prevalence than males, multibacillary patients higher than paucibacillary patients, and in-patients higher than out-patients. Corneal disease was the most common cause of blindness in study groups, followed by iritic disease and cataract; while the main cause of poor vision was cataract, then corneal and iritic diseases. Treatable blindness accounted for 62.7% of the cases and treatable poor vision for 88.6% of the patients studied. 56.62% of cases with eye complications expressed their willingness to be treated. CONCLUSIONS: Although prevention and treatment of low vision and blindness in leprosy patients is very hard, it is necessary for doctors and medical workers to make clear of the factors to cause low vision and blindness, especially those in leprosy patients so that some measures for prevention and treatment of the disease could be taken accordingly.

Comprehensive treatment of complicated plantar ulcers in leprosy

OBJECTIVE: To investigate feasible treatment methods for plantar ulcers in leprosy patients according to the agreement between the Ministry of Health (MOH) of China and the Leprosy Mission International (LMI). METHODS: A total of 2599 complicated foot ulcers in 1804 leprosy cases underwent surgic treatment. Plastic fixation and supports were used, dressings were changed regularly, and protective footwear and modified insoles were provided. RESULTS: Of the 2599 foot ulcers 1446 (55.64%) healed. The cure rate of the patients treated in leprosy hospitals was 71.31%, with 219 (15.15%) recurrences of foot ulcers. The recurrence rate of those who lived at home was 18.35%. CONCLUSIONS: Comprehensive treatment of foot ulcers has a high cure rate and a low recurrence rate. Reduction of workload, avoidance of long distance walking, intensification of education on foot self-care and provision of financial support are the main measures for preventing a recurrence of foot ulcers.