Serodiagnosis of paucibacillary and multibacillary leprosy using a recombinant chimeric protein composed of specific B-cell epitopes derived from Mycobacterium leprae proteins.

Leprosy diagnosis is difficult due to the clinical similarity with other infectious diseases, and laboratory tests presents problems related to sensitivity and/or specificity. In this study, we used bioinformatics to assess Mycobacterium leprae proteins and formulated a chimeric protein that was tested as a diagnostic marker for the disease. The amino acid sequences from ML0008, ML0126, ML0308, ML1057, ML2028, ML2038, ML2498 proteins were evaluated, and the B-cell epitopes QASVAYPATSYADFRAHNHWWNGP, SLQRSISPNSYNTARVDP and QLLGQTADVAGAAKSGPVQPMGDRGSVSPVGQ were considered M. leprae-specific and used to construct the gene encoding the recombinant antigen. The gene was constructed, the recombinant protein was expressed, purified and tested in ELISA using 252 sera, which contained samples from multibacillary (MB) or paucibacillary (PB) leprosy patients, from their household contacts and healthy individuals, as well as from patients with Chagas disease, visceral and tegumentary leishmaniases (VL/TL), malaria, tuberculosis, and HIV. Sensitivity (Se) and specificity (Sp) for MB and PB samples compared to sera from both healthy subjects and individuals with cross-reactive diseases were 100%. The Se value for MB and PB samples compared to sera from household contacts was 100%, but Sp was 64%. In conclusion, data suggest that this protein could be considered in future studies for leprosy diagnosis.

Zinc finger protein 263 upregulates interleukin 33 and suppresses autophagy to accelerate the malignant progression of non-small cell lung cancer / La proteína 263 con dedos de zinc regula positivamente la interleucina 33 y suprime la autofagia para acelerar la progresión maligna del cáncer de pulmón de células no pequeñas

Purpose: Non-small cell lung cancer (NSCLC) is a complex disease that remains a major public health concern worldwide. One promising avenue for NSCLC treatment is the targeting of transcription factors that regulate key pathways involved in cancer progression. In this study, we investigated the role of the transcription factor ZNF263 in NSCLC and its impact on the regulation of IL33, apoptosis, and autophagy. Methods: Levels of ZNF263 in tissues and cell lines were identified, after which the effects of its knockdown on cellular malignant behaviors, apoptosis and autophagy were assessed. Based on bioinformatics analysis, ZNF263 was found to bind to IL33 promoter, their mutual relationship was confirmed, as well as the role of IL33 in the regulation of ZNF263. The involvement of ZNF263 in the growth of xenograft tumors was assessed using tumor-bearing nude mouse models. Results: Experimental results revealed that ZNF263 was upregulated in NSCLC tissue samples and cell lines. Its expression level is positively correlated with cellular malignant behaviors. We further demonstrated that ZNF263 upregulated IL33 expression, which, in turn, promoted the proliferation and migration, inhibited apoptosis and autophagy in NSCLC cells. Furthermore, ZNF263 knockdown reduced the growth of xenograft tumors in nude mice. Conclusion: This finding suggests that the inhibition of ZNF263 or IL33 may represent a novel therapeutic strategy for NSCLC. Importantly, our results highlight the crucial role of transcription factors in NSCLC and their potential as therapeutic targets.(AU)

A morphological review of medial malleolar fractures - A large single centre series.

BACKGROUND: Many approaches to management of medial malleolar fractures are described in the literature however, their morphology is under investigated. The aim of this study was to analyse the morphology of medial malleolar fractures to identify any association with medial malleolar fracture non-union or malunion. METHODS: Patients who had undergone surgical fixation of their MMF were identified from 2012 to 2022, using electronic patient records. Retrospective analysis of their preoperative, intraoperative, and postoperative radiographs was performed to determine their morphology and prevalence of non-union and malunion. Lauge-Hansen classification was used to characterise ankle fracture morphology and Herscovici classification to characterise MMF morphology. RESULTS: A total of 650 patients were identified across a 10-year period which could be included in the study. The overall non-union rate for our cohort was 18.77% (122/650). The overall malunion rate was 6.92% (45/650). Herscovici type A fractures were significantly more frequently mal-reduced at time of surgery as compared to other fracture types (p = .003). Medial wall blowout combined with Hercovici type B fractures showed a significant increase in malunion rate. There is a higher rate of bone union in patients who had been anatomically reduced. CONCLUSION: The morphology of medial malleolar fractures does have an impact of the radiological outcome following surgical management. Medial wall blowout fractures were most prevalent in adduction-type injuries; however, it should not be ruled out in rotational injuries with medial wall blowouts combined with and Herscovici type B fractures showing a significant increase in malunions. Herscovici type A fractures had significantly higher malreductions. LEVEL OF EVIDENCE: Level 3 - Retrospective Cohort Study.

Quantifying assumptions underlying peak oxygen consumption equations across the body mass spectrum.

The goal of this study is to quantify the assumptions associated with the Wasserman-Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO2) equations across body mass index (BMI). Assumptions in pVO2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent-predicted VO2 (ppVO2) values for both equations and compared them using the Bland-Altman method. Assumptions associated with pVO2 across BMI categories were quantified by comparing the slopes of age-adjusted VO2 ratios (pVO2/pre-exercise VO2) and ppVO2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m2, pVO2 26.8 mlO2/kg/min). The Bland-Altman plot revealed an average relative difference of -1.7% (95% CI: -2.1 to -1.2%) between WH and FRIEND ppVO2 values with greater differences among those with obesity. Analysis of the VO2 ratio to ppVO2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO2 may better inform the clinical interpretation of ppVO2 values during cardiopulmonary exercise test evaluations.

Dermoscopic features of nails in Leprosy patients in a tertiary referral hospital in West Java, Indonesia.

INTRODUCTION: Leprosy is a chronic granulomatous infectious disease, mainly affecting the skin and peripheral nerves, caused by the obligate intracellular bacteria Mycobacterium leprae. The disease has been discussed in several review articles in recent research, but as far as we know, only a few have addressed the effects of leprosy on nails, especially those who examine the dermoscopic features of nails in leprosy patients. PURPOSES: We aimed to document nail changes in leprosy patients and identify any particular findings through dermoscopic examination. METHOD: This was an observational study conducted in the Dermatology and Venereology Clinic of Hasan Sadikin Hospital, West Java, Indonesia, from March 2023 through May 2023. All patients have established cases of leprosy, and the diagnosis is based on clinical and bacteriological examinations. Recruitment was done through total sampling. Dermoscopic examination of all fingernails and toenails was performed at 10x magnification using a handheld dermatoscope (Heine DELTA 20 T Dermatoscope) in polarized mode without the linkage fluid to document the dermoscopic features. RESULT: Of a total of 19 patients, 15 had nail changes due to leprosy. Out of 15 patients, 13 patients were male. Patients below 25 years old had more nail changes. Most of the patients had a duration of disease greater than two years. Both fingers and toes were involved in nine patients. In this study, the most common dermoscopic feature found was the longitudinal ridge. Other dermoscopic features found in this study were transverse lines, onycholysis, longitudinal melanonychia, leukonychia, subungual hemorrhage, subungual hyperkeratosis, anonychia, and onychorrexis. CONCLUSION: Nail changes are found in leprosy patients and have a wide variety of clinical appearances. A dermoscopy should be performed to assess nail changes in leprosy.

Macrophage immunophenotypes in Jorge Lobo's disease and lepromatous leprosy- A comparative study.

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells.

Non-Tuberculous Mycobacterial isolates from Panama: A retrospective 5-year analysis (2017-2021).

BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.

Temporary Cast Application in Dislocated Ankle Fractures Leads to High Rates of Secondary Loss of Reduction: Does the Lauge-Hansen Injury Type Matter?

BACKGROUND: For the temporary treatment of ankle fracture dislocations (AFDs), previous studies indicate higher rates of secondary loss of reduction (LOR) with splint immobilization, prompting consideration for expanding indications for external fixation (ExFix). However, these studies did not investigate the influence of fracture morphology to further improve patient selection. The aim of this study was to investigate the influence of Lauge-Hansen injury type on the LOR rate in bimalleolar or trimalleolar AFDs for temporary cast vs ExFix immobilization. METHODS: In this retrospective cohort study, patients with isolated AFD cases treated at our institution from 2011 to 2020 were reviewed. Inclusion criteria required radiographs depicting initial dislocation and appropriate reduction after Cast or ExFix immobilization. Exclusion criteria encompassed concomitant injuries, open fractures, conservative management as well as surgery performed within 48 hours or at a different facility. Patients were grouped by temporary treatment (Cast or ExFix). The primary endpoint was LOR prior to definitive surgery across various Lauge-Hansen types. RESULTS: The LOR rate was significantly higher in the cast group (40/152, 26.3%) compared to the ExFix group (5/191, 2.6%; P < .0001). In the cast group, LOR was associated with an increase in time to definitive surgery by a mean of 3 days (P < .002). During cast treatment, LOR was significantly more likely for pronation abduction (P = .001) and supination external rotation injuries (P < .0001), whereas no significant differences were observed for pronation external rotation (P = .006), supination adduction (P > .99), and fractures not classifiable (P > .99). CONCLUSION: In cases of AFDs resulting from supination external rotation or pronation abduction trauma according to the Lauge-Hansen classification, especially in the setting of an additional posterior malleolar fracture, primary application of external fixation should be considered to reduce the risk for secondary loss of reduction. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Brevipalpus yothersi Baker (Tenuipalpidae) development in sweet orange plants is influenced by previous mite infestation and the presence of shelters.

Citrus leprosis is the most important viral disease affecting citrus. The disease is caused predominantly by CiLV-C and is transmitted by Brevipalpus yothersi Baker mites. This study brings some insight into the colonization of B. yothersi in citrus [(Citrus × sinensis (L.) Osbeck (Rutaceae)] previously infested by viruliferous or non-viruliferous B. yothersi. It also assesses the putative role of shelters on the behavior of B. yothersi. Expression of PR1 and PR4 genes, markers of plant defense mechanisms, were evaluated by RT-qPCR to correlate the role of the plant hormonal changes during the tri-trophic virus-mite-plant interplay. A previous infestation with either non-viruliferous and viruliferous mites positively influenced oviposition and the number of adult individuals in the resulting populations. Mite populations were higher on branches that had received a previous mite infestation than branches that did not. There was an increase in the expression of PR4, a marker gene in the jasmonic acid (JA) pathway, in the treatment with non-viruliferous mites, indicating a response from the plant to their feeding. Conversely, an induced expression of PR1, a marker gene in the salicylic acid (SA) pathway, was observed mainly in the treatment with viruliferous mites, which suggests the activation of a plant response against the pathogen. The earlier mite infestation, as well as the presence of leprosis lesions and a gypsum mixture as artificial shelters, all fostered the growth of the B. yothersi populations after the second infestation, regardless of the presence or absence of CiLV-C. Furthermore, it is suggested that B. yothersi feeding actually induces the JA pathway in plants. At the same time, the CiLV-C represses the JA pathway and induces the SA pathway, which benefits the mite vector.

From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

Bioarchaeological investigation of individuals with suspected multibacillary leprosy from the mediaeval leprosarium of St Mary Magdalen, Winchester, Hampshire, UK.

Introduction. We have examined four burials from the St Mary Magdalen mediaeval leprosarium cemetery in Winchester, Hampshire, UK. One (Sk.8) was a male child, two (Sk.45 and Sk.52) were adolescent females and the fourth (Sk.512) was an adult male. The cemetery was in use between the 10th and 12th centuries. All showed skeletal lesions of leprosy. Additionally, one of the two females (Sk.45) had lesions suggestive of multi-cystic tuberculosis and the second (Sk.52) of leprogenic odontodysplasia (LO), a rare malformation of the roots of the permanent maxillary incisors.Gap statement. Relatively little is known of the manifestations of lepromatous leprosy (LL) in younger individuals from the archaeological record.Aims and Methodology. To address this, we have used ancient DNA testing and osteological examination of the individuals, supplemented with X-ray and microcomputed tomography (micro-CT) scan as necessary to assess the disease status.Results and Conclusions. The presence of Mycobacterium leprae DNA was confirmed in both females, and genotyping showed SNP type 3I-1 strains but with a clear genotypic variation. We could not confirm Mycobacterium tuberculosis complex DNA in the female individual SK.45. High levels of M. leprae DNA were found within the pulp cavities of four maxillary teeth from the male child (Sk.8) with LO, consistent with the theory that the replication of M. leprae in alveolar bone may interfere with root formation at key stages of development. We report our biomolecular findings in these individuals and review the evidence this site has contributed to our knowledge of mediaeval leprosy.

Eyebrow trichoscopy in leprosy.

BACKGROUND: Trichoscopy is a noninvasive technique based on the analysis of hair structures and the scalp, which allows for early diagnosis of different forms of alopecia. METHODS: We conducted a descriptive cross-sectional study in the Dermatology Department of Hospital Universitario "Dr. José Eleuterio González" in Monterrey, Northeastern Mexico. We included 25 patients with a confirmed diagnosis of leprosy. Ten dermoscopic characteristics were assessed in the eyebrows of these patients. Images of the medial and distal portions of the eyebrows were included. Cohen's kappa coefficient was used for the analysis of coherence between the findings of two dermatologists. RESULTS: Of the 25 patients, 14 were male (56%) and 11 were female (44%), with a median age of 60.28 years (IQR: 40-87). The most common findings in the medial eyebrow included vellus hair (96%) and white-yellowish structureless areas (84%). Furthermore, the most common features of the distal eyebrow included vellus hair (96%), white yellowish structureless areas (92%), and pinpoint white dots (92%). CONCLUSIONS: To the best of our knowledge, this study is the first of its kind to describe trichoscopy findings in different leprosy subtypes and classify them into medial and distal eyebrow findings, which seem to be the most affected areas. Identification of these changes is easier in the distal portion of the eyebrows in every subtype of leprosy. We also discovered new trichoscopic findings in the eyebrows: perifollicular hyperpigmentation and yellow dots.

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

BACKGROUND: Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. METHODS: In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. FINDINGS: A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). CONCLUSION: TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

Effect of chronic heavy tobacco smoking on ankle fracture healing.

INTRODUCTION: Tobacco smoking is linked to an elevated risk of osteomyelitis and delayed healing in long bone fractures. However, the impact of smoking on bone union and soft tissue recovery following ankle fractures remains unclear. This study presents a retrospective comparative analysis evaluating the effects of chronic heavy tobacco smoking on the healing process and outcomes of ankle fractures after surgical interventions. MATERIALS AND METHODS: We examined 220 consecutive cases of chronic heavy smokers (CHS) with closed ankle fractures who were referred to our unit for further treatment. A control group, consisting of 220 age- and sex-matched individuals (non-smokers with closed ankle fractures), was identified for comparative analysis. We collected clinical data, including pre-existing comorbidities, Lauge-Hansen fracture classification, necessity for surgery, and the surgical procedures performed. The primary outcomes investigated were the time required for fracture union and wound healing. Secondary outcomes included postoperative complications such as prolonged pain, bleeding, swelling, infection, compartment syndrome, and neurovascular impairment, as well as the incidence of delayed union, non-union, and the need for further intervention. Both cohorts were monitored for a minimum of 24 months. RESULTS: Our analysis revealed that the surgical cohort of chronic heavy smokers exhibited a statistically significant delay in fracture union compared to both the conservatively managed smokers and the control group. Further scrutiny of the surgical cohort of chronic smokers indicated a significant correlation between smoking and extended postoperative pain duration, persistent swelling at the fracture site, and both superficial and deep wound infections. Additionally, these patients experienced delays in both fracture union and wound healing when compared to the control group. Similarly, the conservatively managed chronic smokers showed a marginal increase in the incidence of post-injury pain duration, extended swelling at the fracture site, and delayed union compared to the control group. CONCLUSION: Patients who are chronic heavy smokers and require surgical intervention for ankle fractures should be made aware of their increased risk for delayed fracture union and poor wound healing. Orthopedic surgeons should proactively encourage these patients to participate in smoking cessation programs.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Prevalence Trend and Clinical Profile of Leprosy Among the Indigenous Penan Community in Rural Baram, Sarawak, Malaysia: A Retrospective Study.

In Malaysia, despite achieving leprosy-elimination status in 1994, leprosy remains a public health issue among the indigenous Penan community in Sarawak. This study aimed to determine the prevalence trend and clinical profile of leprosy among the Penans in rural Baram, Sarawak, Malaysia. A retrospective records review was conducted on 10-year (2008-2018) time trend of annual prevalence rate and 5-year (2013-2018) Penan leprosy patient clinical profile. Out of the 257 new cases of leprosy reported in Sarawak, 42.8% were Penans, and 72.7% were from Baram. The annual Penan ethnic-specific prevalence rate ranged from 2.08 to 35.5/10 000. Forty-six cases were analyzed for clinical profile: There were more males, active case detection, and multibacillary leprosy. The prevalence trend of leprosy among the Penans in rural Baram exceeded recommended elimination targets. Majority of the cases were detected through active case detection, but cases were detected late. Interventions are needed to improve early diagnosis and detection to achieve elimination of leprosy.

MicroRNAs correlate with bacillary index and genes associated to cell death processes in leprosy.

Mycobacterium leprae infects skin and peripheral nerves causing a broad of clinical forms. MicroRNAs (miRNAs) control immune mechanisms such as apoptosis, autophagy as well as to target genes leading to abnormal proliferation, metastasis, and invasion of cells. Herein we evaluated miRNAs expression for leprosy phenotypes in biopsies obtained from patients with and without reactions. We also correlated those miRNAs with both, bacillary index (BI) and genes involved in the micobacteria elimination process. Our results show a significant increase in the miR-125a-3p expression in paucibacillary (PB) patients vs multibacillary (MB) subjects (p = 0.007) and vs reversal reactions (RR) (p = 0.005), respectively. Likewise, there was a higher expression of miR-125a-3p in patients with erythema nodosum leprosum (ENL) vs MB without reactions (p = 0.002). Furthermore, there was a positive correlation between miR-125a-3p, miR-146b-5p and miR-132-5p expression and BI in patients with RR and ENL. These miRNAS were also correlated with genes such as ATG12 (miR-125a-3p), TNFRSF10A (miR-146b-5p), PARK2, CFLAR and STX7 (miR-132-5p). All together we underpin a role for these miRNAs in leprosy pathogenesis, implicating mechanisms such as apoptosis and autophagy in skin. The miR-125a-3p might have a distinct role associated with PB phenotype and ENL in MB patients.

Task sharing for the management of leprosy by nurses in a tertiary healthcare setting of Northern India.

BACKGROUND: This study aimed to assess the effectiveness of nurse-led interventions in managing leprosy due to a shortage of dermatologists and other healthcare professionals. METHODS: A total of 100 leprosy patients were divided into experimental (n=50) and control groups (n=50). The intervention included face-to-face counseling by a trained nurse, motivational videos and exercise demonstrations. The control group received standard care. The primary outcome of interest was treatment adherence (Adherence to Refills and Medications Scale); other assessed outcomes included changes in perceived stigma (Stigma Assessment and Reduction of Impact scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder seven-item) and quality of life (WHO QOL-BREF Scale) from baseline to week 8. RESULTS: The intervention group had better treatment adherence (p<0.001). At baseline, moderately severe and severe depression prevalence was 18% and 28%, respectively, and anxiety was 25%, with no intergroup differences. Anxiety significantly decreased in the intervention group (p<0.001), but depression remained similar (p=0.291). Perceived stigma improved notably, especially in disclosure of concern (p<0.001), internal stigma (p<0.001) and anticipated stigma (p<0.001). Quality of life scores improved in the intervention group vs controls. CONCLUSION: Nurse-led interventions effectively enhanced quality of life and treatment adherence and reduced anxiety, depression and perceived stigma among leprosy patients. The study recommends strengthening the capacity of nurses for active involvement in leprosy care.