Molecular epidemiological characteristics of Mycobacterium leprae in highly endemic areas of China during the COVID-19 epidemic.

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

Overview and Current Advances in Dapsone Hypersensitivity Syndrome.

PURPOSE OF REVIEW: As a sulfone antibacterial agent, dapsone has been widely used to treat leprosy. Moreover, dapsone is also used in many immune diseases such as herpetic dermatitis because of its anti-inflammatory and immunomodulatory effects. However, dapsone can cause several adverse effects, the most serious being dapsone hypersensitivity syndrome. Dapsone hypersensitivity syndrome is characterized by a triad of eruptions, fever, and organ involvement, which limits the application of dapsone to some extent. RECENT FINDINGS: In this article, we review current research about the interaction model between HLA-B*13:01, dapsone, and specific TCR in dapsone-induced drug hypersensitivity. In addition to the proposed mechanisms, we also discussed clinical features, treatment progress, prevalence, and prevention of dapsone hypersensitivity syndrome. These studies reveal the pathogenesis, clinical features, and prevalence from the perspectives of genetic susceptibility and innate and adaptive immunity in dapsone hypersensitivity syndrome, thereby guiding clinicians on how to diagnose, prevent, and treat dapsone hypersensitivity syndrome.

Global prevalence of resistance to rifampicin in Mycobacterium leprae: A meta-analysis.

OBJECTIVES: As the only bactericidal drug in multidrug therapy is rifampicin, monitoring of antimicrobial resistance is important in leprosy patients. Therefore, we conducted a meta-analysis on the resistance of Mycobacterium leprae (M. leprae) to rifampicin and estimated drug resistance in different therapeutic states and regions. METHODS: Embase, Medline, PubMed, and Web of Science were searched to identify studies between 1 January 1993 and 1 January 2022. Two independent reviewers extracted study data. Pooled cumulative incidences were computed using random-effects meta-analyses. RESULTS: We included 32 papers describing the resistance of M. leprae to rifampicin (pooled cumulative incidences, 11% [95% confidence interval {CI}, 7% to 15%]). Therapeutic states and regional distribution were obtained for subgroup analyses. A total of 51 of 1135 new cases (pooled incidence, 10% [95% CI, 5% to 16%]) and 81 of 733 relapsed cases (pooled incidence, 20% [95% CI, 13% to 27%]) had rifampicin resistance. A total of 139 participants, including 11 patients with rifampicin resistance (pooled incidence, 42% [95% CI, -21% to 105%]), were nonresponsive and intractable cases. The incidence of rifampicin resistance was highest in the Western Pacific (pooled incidence, 21% [95% CI, 13% to 29%]) and lowest in the Americas (pooled incidence, 4% [95% CI, 1% to 7%]). CONCLUSIONS: Drug resistance testing and a robust and rigorous surveillance system are recommended to detect the prevalence of drug resistance in leprosy.

Molecular Surveillance of Antimicrobial Resistance of Mycobacterium leprae from Leprosy Patients in Zhejiang Province, China.

Purpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province. Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy. Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases. Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.

Risk factors for dapsone resistance in leprosy patients: a systematic meta-analysis.

OBJECTIVES: Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn assisting in implementing better control strategies for leprosy elimination. METHODS: A systematic literature search was conducted in PubMed, Embase, Medline, and Web of Science. Two independent reviewers selected the literature according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), extracted data, and evaluated the risk of bias. Drug resistance data were pooled using the random-effects model. Subgroup analysis was performed based on across sampling time, region, study population (treatment status, relapses status), and sample size. RESULTS: A total of 30 studies were included. The results of meta-analysis showed that the dapsone resistance rate of leprosy patients after treatment was 8% (95% confidence interval [CI], 6%-10%). Compared to the rates of primary resistance of new cases without treatment therapy (pooled incidence, 4% [95% CI, 2%-5%]), treatment cases (13% [95% CI 9%-16%]) had secondary resistance, and relapse cases (26% [95% CI, 18%-33%]) had drug resistance. In addition, the drug resistance rate of monotherapy was significantly increased than that of relapsed patients treated with diamino-diphenylsulfone monotherapy. Subgroup analysis showed that the patients in the Western Pacific have the highest dapsone resistance, and the resistance to dapsone was slightly lower after 2005. For sample size, the rate in the group under 100 samples was significantly higher than in the other. CONCLUSION: Dapsone resistance is closely related to leprosy relapse and long-term drug use. Dapsone monotherapy is one of important reasons for drug resistance in relapsed cases. Drug resistance varies among different populations and regions of the world.

3D Mapping of the Lateral Malleolus Fractures for Predicting Syndesmotic Injuries in Supination External Rotation Type Ankle Fractures.

Supination external rotation (SER) type ankle fracture is the most common ankle fracture in the Lauge-Hansen classification and is often accompanied with syndesmotic injury. However, the mechanism of this injury is indistinct and a suggestive role can be given by preoperative imaging. This study was to preoperatively predict whether SER type ankle fractures are accompanied with syndesmotic injuries by the means of lateral malleolus fracture mapping. One hundred and forty-eight patients diagnosed with SER type ankle fractures were retrospectively enrolled in this study. The baseline data were collected and computed tomography data were reconstructed in 3-dimensional (3D) model. Patients were divided into stable and unstable groups according to intraoperative Cotton test and whether the inferior tibiofibular screw was placed. All fracture lines were superimposed on the ankle template to create a fracture map, and the data on the fracture map were further measured. Logistic regression was conducted to identify relevant factors and the cutoff values were given using receiver operating characteristic curves. Forty-one patients were enrolled in the unstable group and 107 patients were enrolled in the stable group. The lateral malleolus fracture lines of the unstable group were higher and steeper than that in the stable group on lateral and posterior views. The fracture height of the posterior cortex and peak height were the significant contributing factors, and the cut-off values of posterior cortex, peak height and inclination angle were 40.35 mm (sensitivity: 78%, specificity: 82%), 55.34 mm (sensitivity: 85%, specificity: 70%) and 55.6° (sensitivity: 66%, specificity: 86%), respectively. In general, when the fracture lines of the lateral malleolus were high and steep, it was usually indicative of a syndesmotic injury and can be predicted by the preoperative 3D reconstruction of fracture height of posterior cortex, peak height and inclination angle. If the cut-off values of these indicators are exceeded, the syndesmotic injuries may be presented and need to be verified in the intraoperative Cotton test to decide whether to insert an inferior tibiofibular screw.