Plantar pressure distribution and altered postural control in multibacillary leprosy patients.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, predominantly affecting the peripheral nerves, resulting in sensory and motor deficits in the feet. Foot ulcers and imbalances are frequent manifestations in leprosy, often correlating with diminished sensitivity. While clinical scales and monofilament esthesiometers are conventionally utilized to evaluate foot sensitivity and balance in these patients, their discriminatory power is limited and their effectiveness is greatly dependent on the examiner's proficiency. In contrast, baropodometry and posturography offer a more comprehensive evaluation, aiming to preempt potential damage events. This study aimed was to assess the correlation between baropodometry and force plate measurements in leprosy patients and control participants, to improve the prevention and treatment of foot ulcers and complications associated with leprosy. METHODOLOGY: This cross-sectional study was conducted during 2022 and enrolled 39 participants (22 patients with multibacillary leprosy and 17 non-leprosy controls). Demographic data were collected, and a monofilament esthesiometer was used to assess sensory deficits. In addition, physical examinations and balance and plantar pressure tests were conducted. The Student's t-test was used to compare mean and maximum plantar pressures between groups. For most COP variables, a Mann-Whitney Wilcoxon test was used, except for AP amplitude which was analyzed with the Student's t-test due to its normal distribution. The relationship between foot pressure and balance control was assessed using Spearman's correlation, focusing on areas with significant pressure differences between groups. PRINCIPAL FINDINGS: Leprosy patients showed increased pressure in forefoot areas (T1, M1, T2-T5, and M2) and decreased pressure in hindfoot regions (MH and LH) compared to controls. These patients also displayed higher AP and ML amplitudes, suggesting poorer COP control. Correlation analyses between the two groups revealed that foot plantar pressures significantly impact balance control. Specifically, increased T1 region pressures correlated with greater sway in balance tasks, while decreased MH region pressures were linked to reduced COP control. CONCLUSIONS/SIGNIFICANCE: The findings suggest a joint disturbance of plantar pressure distribution and static balance control in leprosy patients. These alterations may increase the risk of tissue injuries, including calluses and deformities, as well as falls.

Factors Associated with High Prevalence of Multibacillary Leprosy in West Bengal: A Case-Control Study.

BACKGROUND: High proportion of multibacillary (MB) among newly diagnosed leprosy cases poses a public health challenge. OBJECTIVES: This study aimed to find out the factors associated with the high burden of MB leprosy in West Bengal. MATERIALS AND METHODS: This case-control study was conducted from August 2020 to December 2022 in three high-endemic districts (annual new case detection rate ≥10/lakh) of West Bengal. OBJECTIVES: MB cases registered under the National Leprosy Eradication Programme were considered as case and paucibacillary (PB) cases were considered as control. Weighted sample sizes for cases and controls in each of the three districts were selected using simple random sampling from the list of registered leprosy patients. Requisite data were collected through structured interview with a validated questionnaire in Bengali. R, version 4.1.1 (R Foundation for Statistical Computing, 2021, Vienna, Austria) was used for data analysis. A binary logistic regression model was prepared with the type of leprosy as a dependent variable. RESULTS: Three hundred and ninety-eight individuals, 204 MB and 194 PB, participated in this study with 1.97% nonresponse rate. Gender, marital status, and diagnostic delay (adjusted odds ratio = 2.75 [1.66,4.65]) were associated with developing MB. Not perceiving the symptoms seriously (90, 56% [PB], 97, 51% [MB]), lack of knowledge about the disease and its complications (47, 29% [PB], 53, 28% [MB]), delayed referral by the private practitioners (11, 7% [PB], 22, 12% [MB]) were the major reasons of delay. CONCLUSION: This study identified a vulnerable group - married and migrated males. Changing from annual screening to quarterly screening along with capacity building and awareness generation of the targeted population is the need of the hour for eradicating the disease.

Transcription Factor HES-1: How Is the Expression of This Transcriptional Factor in Paucibacillary Leprosy Patients?

INTRODUCTION: Leprosy is an ancient and chronic infectious disease caused by 2 mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). Recently, our research group observed that HES-1, an innate cellular component of the Notch signaling pathway, is related to the pathogenesis of leprosy. Therefore, it could be helpful in its detection. OBJECTIVE: To determine the expression of HES-1 in the skin of patients with paucibacillary (PB) leprosy. METHODS: A cross-sectional, descriptive, observational study was conducted. Forty-five skin samples from patients with leprosy were evaluated (30 samples from MB leprosy and 15 from PB leprosy) using immunohistochemistry of HES-1 and S-100. RESULTS: PB leprosy biopsies revealed a reduction of HES-1 in 66.7% of the epidermis, 80% of the eccrine glands, and 62.5% of the hair follicles of these patients, with statistical differences in the control group (P < 0.0001). Besides, HES-1 showed similar utility to S-100 immunostaining in detecting the MB and PB leprosy. CONCLUSIONS: HES-1 is a transcriptional factor also reduced in PB patients' epidermis and skin appendages. Finally, our data show that HES-1 could be a biomarker in diagnosing PB and MB leprosy.

Evaluation of the influence of genetic variants in Cereblon gene on the response to the treatment of erythema nodosum leprosum with thalidomide.

BACKGROUND: Erythema nodosum leprosum (ENL) is an acute and systemic inflammatory reaction of leprosy characterised by painful nodules and involvement of various organs. Thalidomide is an immunomodulatory and anti-inflammatory drug currently used to treat this condition. Cereblon (CRBN) protein is the primary target of thalidomide, and it has been pointed out as necessary for the efficacy of this drug in others therapeutics settings. OBJECTIVES: In this study, we aimed to evaluate the influence of CRBN gene variants on the dose of thalidomide as well as its adverse effects during treatment of ENL. METHODS: A total of 103 ENL patients in treatment with thalidomide were included in this study. DNA samples were obtained from saliva and molecular analysis of CRBN gene were performed to investigate the variants rs1620675, rs1672770 and rs4183. Different genotypes of CRBN variants were evaluated in relation to their influence on the dose of thalidomide and on the occurrence of adverse effects. FINDINGS: No association was found between CRBN variants and thalidomide dose variation. However, the genotypes of rs1672770 showed association with gastrointestinal effects (p = 0.040). Moreover, the haplotype DEL/C/T (rs4183/rs1672770/rs1620675) was also associated with gastrointestinal adverse effects (p = 0.015). MAIN CONCLUSIONS: Our results show that CRBN variants affect the treatment of ENH with thalidomide, especially on the adverse effects related to the drug.

Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population.

Leprosy is a chronic neurodermatological disease caused by the bacillus Mycobacterium leprae. Recent studies show that SNPs in genes related to miRNAs have been associated with several diseases in different populations. This study aimed to evaluate the association of twenty-five SNPs in genes encoding miRNAs related to biological processes and immune response with susceptibility to leprosy and its polar forms paucibacillary and multibacillary in the Brazilian Amazon. A total of 114 leprosy patients and 71 household contacts were included in this study. Genotyping was performed using TaqMan Open Array Genotyping. Ancestry-informative markers were used to estimate individual proportions of case and control groups. The SNP rs2505901 (pre-miR938) was associated with protection against the development of paucibacillary leprosy, while the SNPs rs639174 (DROSHA), rs636832 (AGO1), and rs4143815 (miR570) were associated with protection against the development of multibacillary leprosy. In contrast, the SNPs rs10739971 (pri-let-7a1), rs12904 (miR200C), and rs2168518 (miR4513) are associated with the development of the paucibacillary leprosy. The rs10739971 (pri-let-7a1) polymorphism was associated with the development of leprosy, while rs2910164 (miR146A) and rs10035440 (DROSHA) was significantly associated with an increased risk of developing multibacillary leprosy.

Atypical presentations of erythema nodosum leprosum: Diagnostic and therapeutic aspects.

Classic erythema nodosum leprosum (ENL) is characterized clinically by abrupt eruption of tender erythematous nodules, papules and plaques. Variable atypical patterns have been described, for example pustular, bullous, ulcerative, necrotic and Sweet's syndrome-like ENL. We aim to review previously reported cases of atypical ENL addressing the diagnostic and therapeutic aspects of these uncommon presentations. A search of medical literature for all cases of atypical ENL was conducted in the PubMed database till 2020. Data of patients with atypical ENL were collected and analyzed to describe the epidemiological, clinico-histological and therapeutic features. The major five clinically described presentations of atypical ENL include vesiculo-bullous lesions (46 % of patients), ulcero-necrotic lesions (41 %), erythema multiforme-like lesions (28 %), Sweet's syndrome-like lesions (11 %) and pustules (9 %). The skin lesions were accompanied by fever and constitutional symptoms in all patients. Oral steroids and thalidomide were the main lines of therapy in most of the reported patients. Dermatologists and pathologists should keep in mind the clinical variability of ENL to avoid misdiagnosis and delayed management. Early recognition can help control disease progression and save the patients from further complications.

Apremilast in chronic recalcitrant erythema nodosum leprosum: a report of two cases.

Erythema nodosum leprosum (ENL) is a severe immune reaction commonly encountered as a complication in patients with multibacillary leprosy. Management of chronic ENL in leprosy is challenging and necessitates the use of systemic immunosuppressants, including corticosteroids and thalidomide. No single drug is universally effective and most current therapeutic agents carry a significant risk of systemic toxicity. Apremilast is an orally effective phosphodiesterase-4 inhibitor with a potent immunomodulatory action and is clinically effective in inflammatory conditions like chronic plaque psoriasis. We report two patients with poorly controlled chronic ENL, despite the use of multiple therapeutic agents. Both patients demonstrated significant clinical improvement with apremilast, without any adverse effects, thereby suggesting its potential as a novel therapeutic option in chronic ENL. What's already known about this topic? Erythema nodosum leprosum (ENL) is an immune-mediated reaction in patients with multibacillary leprosy, with chronicity and recurrences frequently reported. Management of chronic ENL requires systemic immunosuppressants like corticosteroids, which may not be universally effective and carry a risk of serious toxicity. Apremilast is an oral immunomodulator with good efficacy in inflammatory conditions like chronic plaque psoriasis. What does this study? Apremilast may be an effective therapeutic agent in patients with chronic ENL.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure.

BACKGROUND: Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity. METHODS: We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups. RESULTS: A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years, p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%, p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68, p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002-1.060, p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239-2.060, p < 0.001) were significantly associated with low ADA activity in patients with TPE. CONCLUSIONS: ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.

Hansen Disease (Leprosy) and Armadillo Exposure in Arkansas: A Case Series.

BACKGROUND: Although most cases of Hansen disease (HD) in the United States are imported from endemic areas, a subset of cases are relate to exposure to nine-banded armadillos. Several recent cases of HD in Arkansas occurred in patients who had not traveled to endemic areas and who reported variable degrees of armadillo exposure. OBJECTIVE: The purpose of this study was to report 6 cases of HD diagnosed in Arkansas between 2004 and 2016. The secondary purpose was to explore the correlation between exposure to the nine-banded armadillo as it pertains to transmission of the disease. METHODS: The referring clinician of each patient was contacted to gather information regarding the patient's clinical presentation, armadillo exposure, and travel history. In addition, the Arkansas Department of Health was consulted to review the demographics of individuals diagnosed with HD in the past 15 years and to review the distribution of HD throughout the state of Arkansas. RESULTS: Six domestic cases of HD were associated with both direct and indirect exposure to armadillos. LIMITATIONS: Armadillo exposure may be underreported in patients with HD because of fear of stigmatization and/or lack of access to care. CONCLUSIONS: Direct exposure to armadillos does not appear to be required for transmission of HD making a soil-mediated mechanism of indirect exposure plausible.

IL8 and IL17A polymorphisms associated with multibacillary leprosy and reaction type 1 in a mixed population from southern Brazil.

We evaluated the influence of the IL8 T-738A (nonidentified rs), IL8 T-353A (rs4073), IL17A G197A (rs2275913), and IL17F T7488C (rs763780) single-nucleotide polymorphisms on leprosy. The AA genotype of IL8 T-353A was observed as a risk factor for multibacillary leprosy, regardless of gender and age-of-onset of disease, considering the recessive model (OR, 3.8; 95% CI, 1.1-13.5; P, 0.023). Furthermore, the AA genotype of IL17A G197A was associated with leprosy type 1 reaction (OR, 2.4; 95% CI, 1.1-5.1; P, 0.026) when compared to the group without reaction, which was adjusted for gender and age-of-onset of disease by the model log additive. These results indicate association of IL8 and IL17A polymorphisms with the progression to multibacillary leprosy and with the type 1 reaction, respectively.

Ulcers in leprosy patients, an unrecognized clinical manifestation: a report of 8 cases.

BACKGROUND: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. It is a polymorphic disease with a wide range of cutaneous and neural manifestations. Ulcer is not a common feature in leprosy patients, except during reactional states, Lucio's phenomenon (LP), or secondary to neuropathies. CASES PRESENTATION: We report eight patients with multibacillary leprosy who presented specific skin ulcers as part of their main leprosy manifestation. Ulcers were mostly present on lower limbs (eight patients), followed by the upper limbs (three patients), and the abdomen (one patient). Mean time from onset of skin ulcers to diagnosis of leprosy was 17.4 months: all patients were either misdiagnosed or had delayed diagnosis, with seven of them presenting grade 2 disability by the time of the diagnosis. Reactional states, LP or neuropathy as potential causes of ulcers were ruled out. Biopsy of the ulcer was available in seven patients: histopathology showed mild to moderate lympho-histiocytic infiltrate with vacuolized histiocytes and intact isolated and grouped acid-fast bacilli. Eosinophils, vasculitis, vasculopathy or signs of chronic venous insufficiency were not observed. Skin lesions improved rapidly after multidrug therapy, without any concomitant specific treatment for ulcers. CONCLUSIONS: This series of cases highlights the importance of recognizing ulcers as a specific cutaneous manifestation of leprosy, allowing diagnosis and treatment of the disease, and therefore avoiding development of disabilities and persistence of the transmission chain of M. leprae.

Development of a combined RLEP/16S rRNA (RT) qPCR assay for the detection of viable M. leprae from nasal swab samples.

BACKGROUND: Leprosy continues to be a health problem in endemic areas. More than 200,000 new cases of leprosy per year suggest that transmission of the disease is still ongoing, presumably as airborne infection through nasal droplets. Late diagnosis supports continued transmission and increases the individual risk for functional disabilities. Laboratory tools are considered beneficial to facilitate early detection and clinical assessment of cases. The aim of this study was to validate molecular tools allowing detection, quantification and assessment of viability of M. leprae from nasal swab samples which are easy to obtain without the need of any invasive procedures. METHODS: Validation of two real-time PCRs detecting M. leprae DNA (RLEP qPCR) and RNA (16S rRNA RT qPCR) was conducted on "must not detect"/"must detect" samples and 160 pre-treatment nasal swab samples from 20 clinically diagnosed multibacillary (MB) leprosy patients from Togo. RESULTS: Both assays were 100% M. leprae specific and showed analytical sensitivities of three templates each. Out of 20 clinically diagnosed MB leprosy patients, 15 (75.0%) had a positive RLEP qPCR result from nasal swab samples. The 16S rRNA RT qPCR detected viable bacilli in nasal swab samples of ten out of these 15 RLEP positive patients (66.7%). CONCLUSION: The combined RLEP/16S rRNA (RT) qPCR assay provides a sensitive and specific tool to determine the bacterial load and viability of M. leprae from nasal swab samples and is applicable for early diagnosis, monitoring treatment response and investigating the role of nasal carriage of M. leprae in human-to-human transmission through aerosol infection.

Performance of serological tests PGL1 and NDO-LID in the diagnosis of leprosy in a reference Center in Brazil.

BACKGROUND: Early detection of leprosy and multidrug therapy are crucial to achieve zero transmission and zero grade II incapacities goals of World Health Organization. Leprosy is difficult to diagnose because clinical forms vary and there are no gold standard methods to guide clinicians. The serological rapid tests aid the clinical diagnosis and are available for field use. They are easy to perform, do not require special equipment or refrigeration and are cheaper than the molecular tests. METHODS: We evaluated the performance of two rapid serological tests (PGL1 and NDO-LID) in the discrimination of leprosy cases from healthy individuals at the Alfredo da Matta Foundation, a reference center for the disease in Manaus, Amazonas, Brazil. PGL1 and NDO-LID rapid tests are capable of detecting specific antibodies of M. leprae, IgM and IgM/IgG, respectively. A total of 530 healthy subjects and 171 patients (50 with paucibacillary and 121 multibacillary leprosy) were included in the study. RESULTS: Among the paucibacillary leprosy patients, the sensitivity was 34.0 and 32.0% for the NDO-LID and PGL1, respectively. In multibacillary leprosy patients, the NDO-LID sensitivity was 73.6% and the PGL1 was 81.0%. Serological tests demonstrated specificities of 75.9% for PGL-1 and 81.7% for NDO-LID. The positive predictive value (PPV), negative predictive value (NPV) and accuracy in multibacillary patients were 47.9, 93.1, and 80.2% respectively for the NDO-LID, and 43.4, 94.6 76.8% for PGL1. CONCLUSIONS: The tests showed limited capacity in the diagnosis of the disease, however, the high negative predictive value of the tests indicates a greater chance of true negatives in this group favoring exclusion of leprosy. This characteristic of the ML flow test is important in aiding clinical Diagnosis, especially in a region endemic to the disease and with other confounding skin conditions.

A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China.

BACKGROUND: Patients with leprosy have a very low risk of Alzheimer disease (AD) and ß-amyloid (Aß) deposition is significantly lower in the brain tissue of elderly patients with leprosy compared with age-matched controls. Apolipoprotein E (ApoE) plays a critical role in lipid metabolic pathways and in the brain, facilitating the proteolytic clearance of Aß. We hypothesized that APOE confers risk of leprosy as lipid metabolism is involved in Mycobacterium leprae infection. OBJECTIVES: To investigate the potential genetic associations between APOE and leprosy in two independent Chinese case-control cohorts from the Yuxi and Wenshan prefectures, Yunnan Province of Southwest China. METHODS: Five APOE single-nucleotide polymorphisms (SNPs) were analysed in 1110 individuals (527 patients and 583 controls) from the Yuxi prefecture using a SNaPshot assay. Genetic variations in the entire APOE exons were screened in 1788 individuals (798 patients and 990 controls) from the Wenshan prefecture using next-generation sequencing technology. RESULTS: The AD-associated SNPs rs405509 and rs439401 increased the risk of leprosy per se and multibacillary leprosy (P < 0·005), but the APOE-ε4 allele did not. The SNPs rs405509 and rs439401 were cis expression quantitative trait loci (eQTL) for APOE expression in human skin. Differential APOE mRNA expression was observed in skin lesions of patients with type I reaction leprosy and those with multibacillary leprosy. APOE and related lipid genes are involved in an interaction network with leprosy susceptibility genes. CONCLUSIONS: The APOE gene is associated with leprosy, most likely by regulating lipid-metabolism-related genes.

Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy.

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population.

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

Diffuse Multibacillary Leprosy of Lucio and Latapí with Lucio's Phenomenon, Peru.

Diffuse multibacillary leprosy of Lucio and Latapí is mainly reported in Mexico and Central America. We report a case in a 65-year-old man in Peru. He also had Lucio's phenomenon, characterized by vascular thrombosis and invasion of blood vessel walls by leprosy bacilli, causing extensive skin ulcers.

Distinct Roles of Th17 and Th1 Cells in Inflammatory Responses Associated with the Presentation of Paucibacillary Leprosy and Leprosy Reactions.

It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4+ T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous leprosy (LL) patients. Secondly, inflammatory cytokines were measured by multiplex assay of serum samples from Multibacillary (MB, n = 28) and Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23). Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n = 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed by flow cytometry used to determine the phenotype of cytokine-producing cells. Lesions from TT patients were found to have more CD4+ IL-17A+ cells than those from LL patients. Higher concentrations of IL-17A and IL-1ß were observed in serum from PB than MB patients. The highest serum IFN-γ concentrations were, however, detected in sera from MB patients that developed leprosy reactions (MB LR+ ). Together, these results indicate that Th1 cells were associated with both the PB presentation and also with leprosy reactions. In contrast, Th17 cells were associated with an effective inflammatory response that is present in the PB forms but were not predictive of leprosy reactions in MB patients.