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.

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.

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.

Eficacia de plantillas y zapatos terapéuticos en la reducción de la incidencia de ulceración en pacientes con neuropatía diabética: una revisión sistemática con metaanálisis / Efficacy of insoles and therapeutic shoes in the reduction of the ulceration incidence in diabetic neuropathy patients: A Systematic Review with meta-analysis

Objetivo Investigar el nivel de eficacia de plantillas personalizadas y zapatos terapéuticos en la reducción de la presión plantar y la incidencia de ulceración en presencia de neuropatía diabética. Metodología Las bases de datos PubMed, Scopus, Web of Science, Cinahls, Central Cochrane y Lilacs fueron encuestados en enero de 2020. Se incluyeron ensayos clínicos aleatorizados (ECA) que reportaron pacientes con neuropatía diabética sometidos a intervención con plantillas y calzado terapéutico en comparación con un grupo control. La calidad de las publicaciones se evaluó mediante la escala PEDro y la evidencia mediante la clasificación GRADE. En cuanto al metaanálisis, se realizó la agrupación de datos homogéneos y comparables. Resultados Se incluyeron 11 estudios, lo que resultó en una muestra de 1.443 participantes. Siete artículos presentaron datos suficientes para el metaanálisis. En el corto plazo, el riesgo relativo de protección fue de 0,23 (IC 95%; 0,07; 0,72), mientras que en el largo plazo el riesgo fue de 0,32 (IC 95%; 0,21; 0,48). La escala GRADE señaló baja calidad de evidencia en cuanto a la protección a corto plazo y alta calidad a largo plazo En el análisis cualitativo, seis estudios concluyeron que hubo reducción en la presión plantar del grupo de intervención. Conclusión Se encontró efecto protector del uso de plantillas en el desarrollo de úlceras a corto y largo plazo. (AU)

Objective To investigate the level of efficacy of personalized insoles and therapeutical shoes in plantar pressure and ulceration incidence reduction in the presence of diabetic neuropathy. Methodology The data bases PubMed, Scopus, Web of Science, Cinahls, Central Cochrane and Lilacs were surveyed in January/2020. Randomized clinical trials (RCT) were included that reported diabetic neuropathy patients submitted to intervention with insoles and therapeutical shoes compared to a control group. The quality of the publications was evaluated using the PEDro scale and the evidence by the GRADE classification. Regarding the meta-analysis, the grouping of homogeneous and comparable data was carried out. Results Eleven studies were included, which resulted in a sample containing 1,443 participants. Seven papers presented enough data for the meta-analysis. In the short term, the protection relative risk was 0.23 (IC95% 0.07;0.72), while in the long term, the risk was 0.32 (IC95% 0.21;0.48). The GRADE scale pointed out low evidence quality regarding short-term protection and high quality in the long term. In the qualitative analysis, six studies concluded that there was reduction in the plantar pressure of the intervention group. Conclusion Protective effect of using insoles was found in the development of ulcers in the short and long term. (AU)

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.

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.

Neural leprosy investigation using electroneuromyography and the ML Flow rapid test: a case report.

Neural leprosy, which is characterized by nerve involvement without visible skin lesions, presents a diagnostic challenge. This case report examined the significance of diverse diagnostic modalities in the identification of pure neural leprosy. A 28-year-old patient with symptoms of edema, pain, paresthesia, and diminished sensitivity in the lower limbs underwent various tests. A stilt skin smear yielded negative results on bacilloscopy, whereas a Fast ML Flow leprosy test and electroneuromyography supported the diagnosis. This discussion highlights the importance of accessible methods for early investigation. This study emphasizes the multidisciplinary approach and value of the Fast ML Flow leprosy test and electroneuromyography for diagnosing neural leprosy.

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.

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.

[Hansen's Disease: An Unusual Manifestation of an Ancient Disease]. / Doença de Hansen: Apresentação Incomum de uma Doença Antiga.

Hansen's disease, commonly known as leprosy, is an infectious disease caused by Mycobacterium leprae. Being rare in developed countries, it is an increasingly common imported disease due to the migratory flow from countries where it is endemic. We present the case of a 21-year-old man who went to the emergency department with complaints of additive polyarthralgia involving large joints, papules, and erythematous plaques on the limbs with bullae and central necrosis and fever with chills for one week. Skin biopsy was performed revealing neutrophilic infiltrate with perineural granulomas. The bacilloscopy detected acid-alcohol resistant bacilli. The diagnosis of multibacillary HD with type 2 lepromatous reaction (erythema nodosum leprosum - ENL) was established, showing clinical improvement under corticosteroid therapy. ENL usually presents with painful lesions, being an atypical presentation of leprosy, especially in the presence of bullae and necrosis, making diagnosis difficult and challenging. Social stigma is often present making it difficult to accept the disease as well as adherence to treatment.

A doença de Hansen, vulgarmente conhecida como lepra, é uma doença infecciosa causada por Mycobacterium leprae. Sendo rara nos países desenvolvidos, configura uma doença de importação cada vez mais frequente considerando o fluxo migratório de países onde é endémica. Apresentamos o caso de um homem de 21 anos que recorreu ao serviço de urgência por poliartralgias de caráter aditivo envolvendo grandes articulações, pápulas e placas eritematosas nos membros com bolhas e necrose central e febre com calafrio com uma semana de evolução. Foi realizada biópsia cutânea que revelou infiltrado neutrofílico com granulomas de distribuição perineural e baciloscopia com deteção de bacilos ácido-álcool resistentes. Foi estabelecido o diagnóstico de DH multibacilar com reação lepromatosa tipo 2 (eritema nodoso leproso), apresentando melhoria clínica sob corticoterapia. O eritema nodoso leproso cursa habitualmente com lesões dolorosas, configurando uma apresentação atípica de lepra, sobretudo na presença de bolhas e necrose, tornando este diagnóstico altamente desafiante. O estigma social é frequentemente limitativo na aceitação da doença e adesão ao tratamento.

Five-year pattern of adnexal tumors of the skin in Ethiopia.

BACKGROUND: Adnexal tumors of the skin are rare neoplasms that encompass a wide range of dermatologic entities. Here, we investigated the pattern of adnexal tumors of the skin in the All African Leprosy and Tuberculosis Rehabilitation and Training Center (ALERT) hospital retrospectively. METHODS: A hospital-based retrospective study was conducted at ALERT from histopathology records in the Armauer Hansen Research Institute (AHRI) pathology laboratory of patients diagnosed with any of the skin adnexal tumors during the time period January 2017 to December 2021. A structured data extraction sheet was used. Data entry was done using EpiData 4.6.0.6. Data were analyzed using SPSS version 25. RESULT: A total of 146 skin adnexal tumors were identified making the magnitude 2.8% of total biopsies. The 3rd decade of life was found to be the most common age group. Male-to-female ratio was 1 : 1.05. Majority of the tumors were benign (82.2%) and had sweat gland differentiation at 48.6%. Poroma (10.9%) was the most frequent tumor, whereas porocarcinoma (6.8%) made up the most frequent malignant tumor. The most common site was the head and neck region (48.6%). Only 21.2% of the tumors were correctly identified clinically. CONCLUSION: The magnitude of skin adnexal tumors is found to be slightly higher than other similar studies which could be because it was carried out in the largest dermatologic center in the country. The most common skin adnexal tumors identified, their localizations, and lines of differentiation are all in line with other studies. Histopathologic examination is mandatory for the accurate diagnosis of these tumors.

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.

Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions.

BACKGROUND: C-C motif chemokine ligand 2, a gene that codes for a protein involved in inflammation. Certain SNPs in the CCL2 gene have been studied for their potential associations with susceptibility to various diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in CCL2 may influence the immune response to Mycobacterium leprae infection. OBJECTIVE: To investigate the association of the C-C motif chemokine ligand-2 single nucleotide polymorphisms with leprosy. METHODS: CCL2 single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for CCL2 -2518 A>G, 535 leprosy and 290 controls for CCL2 -362 G>C, 295 leprosy and 240 controls for CCL2 -2134 T>G, 325 leprosy and 288 controls for CCL2 -1549 A>T SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-ß were estimated in sera samples and correlated with CCL2 genotypes. RESULTS: The frequency of the GCT (-2518 A>G, -362 G>C, -2134 T>G) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-2518A>G, p = 0.53), (-362 G>C, p = 0.01), (-2134 T>G, p = 0.10)}. G allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). GG genotype (p = 0.008) and G allele at -2518 (p = 0.030) of the CCL 2 gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -2518 AA and AG genotypes (p = 0.0001). CONCLUSIONS: G allele and GG genotype at the CCL2 -2518 site are associated with a risk of ENL reactions.

High-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults Across the Leprosy Spectrum.

BACKGROUND: High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism. METHODS: From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass, mass to charge ratio m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared. RESULTS: Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (P < .05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism, between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (P < .05). DISCUSSION: Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB versus PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease.

Migration in French Guiana: Implications in health and infectious diseases.

In French Guiana, more than a third of the population, and nearly half of the adults, are of foreign origin. This immigration is explained by the French standard of living, which is attractive to nationals of surrounding countries. Infectious diseases remain in the top 10 causes of premature death, often in the most precarious populations. In this context we aimed to synthesize the state of the knowledge regarding immigration and infectious diseases in French Guiana and the general implications that follow this diagnosis. For HIV, although the majority of patients are of foreign origin, estimates of the presumed date of infection based on CD4 erosion modelling and from molecular analyses suggest that the majority of transmissions in foreign-born individuals occur in French Guiana and that the Guiana shield has been a crossroad between Latin America and the Caribbean. Among key populations bridging these regions illegal gold miners are very mobile and have the greatest proportion B Caribbean HIV viruses. Gold miners have been a key vulnerable population for falciparum malaria and other tropical diseases such as leishmaniasis, leprosy, or leptospirosis. The complex history of migrations in French Guiana and on the Guiana Shield is also reflected in the fingerprinting of mycobacterium tuberculosis and the high incidence of tuberculosis in French Guiana, notably in immigrants, reflects the incidences in the countries of origin of patients. The high burden of infectious diseases in immigrants in French Guiana is first and foremost a reflection of the precarious living conditions within French Guiana and suggests that community-based proactive interventions are crucial to reduce transmission, morbidity, and mortality from infectious diseases.

Challenges and advances in serological and molecular tests to aid leprosy diagnosis.

Leprosy is a neglected chronic infectious disease caused by obligate intracellular bacilli, Mycobacterium leprae and Mycobacterium lepromatosis. Despite multidrug therapy (MDT) success, leprosy accounts for more than 200,000 new cases yearly. Leprosy diagnosis remains based on the dermato-neurologic examination, but histopathology of skin biopsy and bacilloscopy of intradermal scraping are subsidiary diagnostic tests that require expertise and laboratory infrastructure. This minireview summarizes the state of the art of serologic tests to aid leprosy diagnosis, highlighting enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (POCT) biotechnologies. Also, the impact of the postgenomic era on the description of new recombinantly expressed M. leprae-specific protein antigens, such as leprosy Infectious Disease Research Institute (IDRI) diagnostic (LID)-1 is summarized. Highly specific and sensitive molecular techniques to detect M. leprae DNA as the quantitative polymerase chain reaction (qPCR) and the loop-mediated isothermal amplification (LAMP) are briefly reviewed. Serology studies using phenolic glycolipid-I (PGL-I) semi-synthetic antigens, LID-1 fusion antigen, and the single fusion complex natural disaccharide-octyl (NDO)-LID show high sensitivity in multibacillary (MB) patients. However, serology is not applicable to paucibacillary patients, as they have weak humoral response and robust cell-mediated response, requiring tests for cellular biomarkers. Unlike ELISA-based tests, leprosy-specific POCT based on semi-synthetic PGL-I antigens and NDO-LID 1 antigen is easy to perform, cheaper, equipment-free, and can contribute to early diagnosis avoiding permanent incapacities and helping to interrupt M. leprae transmission. Besides its use to help diagnosis of household contacts or at-risk populations in endemic areas, potential applications of leprosy serology include monitoring MDT efficacy, identification of recent infection, especially in young children, as surrogate markers of disease progression to orient adult chemoprophylaxis and as a predictor of type 2 leprosy reactions. Advances in molecular biology techniques have reduced the complexity and execution time of qPCR confirming its utility to help diagnosis while leprosy-specific LAMP holds promise as an adjunct test to detect M. leprae DNA.

Co-infection of Mycobacterium tuberculosis and Mycobacterium leprae Complicated by pulmonary embolism: A rare case report.

A 35-year-old male patient with lepromatous leprosy came to the emergency room (ER) due to breathlessness and chest pain. The patient was diagnosed with pulmonary tuberculosis (TB) after a bronchoscopy and started on antitubercular therapy. However, the patient continued to experience tachycardia and desaturation, and on further evaluation, Computed tomography pulmonary angiography revealed an embolus in the right descending pulmonary artery. The patient was found to have an elevated d-dimer. Further investigation revealed that the cause of the pulmonary thromboembolism (PTE) was the thalidomide medication that the patient was taking for type 2 leprosy reaction. The medication was stopped, and the patient was treated with low-molecular-weight heparin and discharged with apixaban for six months. The patient's condition improved on follow-up. This case is unique due to the rare combination of pulmonary TB, leprosy, and pulmonary embolism brought on by thalidomide administration. Physicians should be aware of the possibility of co-infection of TB and leprosy and the need to rule out thromboembolism when patients are on thalidomide.