Clinical Forms Of Leprosy Research Articles

Role of multisegmental nerve ultrasound in the diagnosis of leprosy neuropathy.

Leprosy is the most common treatable peripheral neuropathy worldwide. The detection of peripheral nerve impairment is essential for its diagnosis and treatment, in order to prevent stigmatizing deformities and disabilities. This study was performed to identify neural thickening through multisegmental ultrasound (US). We assessed US measurements of cross-sectional areas (CSAs) of ulnar, median and tibial nerves at two points (in the osteofibrous tunnel and proximal to the tunnel), and also of the common fibular nerve at the fibular head level in 53 leprosy patients (LP), and compared with those of 53 healthy volunteers (HV), as well as among different clinical forms of leprosy. US evaluation detected neural thickening in 71.1% (38/53) of LP and a mean number of 3.6 enlarged nerves per patient. The ulnar and tibial were the most frequently affected nerves. All nerves showed significantly higher measurements in LP compared with HV, and also greater asymmetry, with significantly higher values for ulnar and tibial nerves. We found significant CSAs differences between tunnel and pre-tunnel points for ulnar and tibial nerves, with maximum values proximal to the tunnel. All clinical forms of leprosy evaluated showed neural enlargement through US. Our findings support the role of multisegmental US as a useful method for diagnosing leprosy neuropathy, revealing that asymmetry, regional and non-uniform thickening are characteristics of the disease. Furthermore, we observed that neural involvement is common in different clinical forms of leprosy, reinforcing the importance of including US evaluation of peripheral nerves in the investigation of all leprosy patients.

Whole mitogenome sequencing uncovers a relation between mitochondrial heteroplasmy and leprosy severity

BackgroundIn recent years, the mitochondria/immune system interaction has been proposed, so that variants of mitochondrial genome and levels of heteroplasmy might deregulate important metabolic processes in fighting infections, such as leprosy.MethodsWe sequenced the whole mitochondrial genome to investigate variants and heteroplasmy levels, considering patients with different clinical forms of leprosy and household contacts. After sequencing, a specific pipeline was used for preparation and bioinformatics analysis to select heteroplasmic variants.ResultsWe found 116 variants in at least two of the subtypes of the case group (Borderline Tuberculoid, Borderline Lepromatous, Lepromatous), suggesting a possible clinical significance to these variants. Notably, 15 variants were exclusively found in these three clinical forms, of which five variants stand out for being missense (m.3791T > C in MT-ND1, m.5317C > A in MT-ND2, m.8545G > A in MT-ATP8, m.9044T > C in MT-ATP6 and m.15837T > C in MT-CYB). In addition, we found 26 variants shared only by leprosy poles, of which two are characterized as missense (m.4248T > C in MT-ND1 and m.8027G > A in MT-CO2).ConclusionWe found a significant number of variants and heteroplasmy levels in the leprosy patients from our cohort, as well as six genes that may influence leprosy susceptibility, suggesting for the first time that the mitogenome might be involved with the leprosy process, distinction of clinical forms and severity. Thus, future studies are needed to help understand the genetic consequences of these variants.

Cytokines profile in pure neural leprosy.

Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its pathophisiology is still poorly understood. Describe the cytokines profile in patients with PNL. 30 Patients diagnosed with PNL in the Souza Araujo Outpatient Clinic and with cytokines evaluated were selected. They were evaluated by neurologists and diagnosed after a nerve biopsy. Serum levels of IL-1 β, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-ϒ, CXCL-10/IP-10 and TGF-β were evaluates at the moment of the diagnosis. Neural thickening was a common clinical finding in this groups of patients. Small and medium sensitive fibers signs and symptoms were present in 92% of the patients and motor involvement in 53%. 43% of patients presented neuropathic pain and no one had neuritis TGF-beta, IL-17, CCl-2 and IP-10. CCL-2 levels were associated with demyelinating patters and IP-10 and IL-1o were associated with axonal patterns at NCS. PNL patients' cytokine profile appears to be different of other clinical forms of leprosy, with the presence of cytokines described in both tuberculoid and lepromatous leprosy. High levels of CCl-2 may be related to the presence of silent neuritis as well as the presence of IL-10. PNL is unique a form of leprosy, therefore, understanding its immunological profiles essential to better understand the disease itself.

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions.

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

Molecular Characterization in 3D Structure of MicroRNA Expressed in Leprosy

Introduction: Hansen's disease, or leprosy is caused by Mycobacterium leprae, is a major public health problem in developing countries, and affecting the skin and peripheral nerves. However, M. leprae can also affect bone tissue, mucous membranes, liver, eyes, and testicles, producing a variety of clinical phenotypes. MicroRNAs (miRNAs) have been expressed in the various clinical forms of leprosy and could potentially be used for its diagnosis.&#x0D; Objective: In silico design of the molecular structure of miRNAs expressed in leprosy. Method: We performed a nucleotide sequence search of 17 miRNAs expressed in leprosy, designing in silico the molecular structure of the following miRNAs: miRNA-26a, miRNA-27a, miRNA-27b, miRNA-29c, miRNA-34c, miRNA-92a-1, miRNA-99a-2, miRNA-101-1, miRNA-101-2, miRNA-125b-1, miRNA-196b, miRNA-425-5p, miRNA-452, miRNA-455, miRNA-502, miRNA-539, and miRNA-660. We extracted the nucleotides were from the GenBank of National Center for Biotechnology Information genetic sequence database. We aligned the extracted sequences with the RNA Folding Form, and the three-dimensional molecular structure design was performed with the RNAComposer.&#x0D; Results: We demonstrate the nucleotide sequences, and molecular structure projection of miRNAs expressed in leprosy, and produces a tutorial on the molecular model of the 17 miRNAs expressed in leprosy through in silico projection processing of their molecular structures.&#x0D; Conclusion: We demonstrate in silico design of selected molecular structures of 17 miRNAs expressed in leprosy through computational biology.

Association between clinical forms of leprosy and contacts with the vaccination state with BCG in five endemic municipalities in the Brazilian Amazon

Introduction: The World Health Organization (WHO) strategy for leprosy control from 2021 to 2030 focuses on interrupting transmission, reducing autochthonous cases to zero, and using a safe and effective vaccine and chemoprophylaxis. In 2020, 127,396 new cases were registered in the world, 19,195 new cases in the Americas, and, of these, 17,979 cases in Brazil, about 93.66% of the total in the Americas. Brazil is classified as a country with a high burden of the disease, occupying the 2nd place in the world, behind only India (WHO, 2020). Análise do período de 2010-2015 em publicação recente9, apresenta as seguintes cidades no estado do Pará nas quais se observou maiores taxas de incidência (detecção): Marituba, Belém, Marabá, Parauapebas e Altamira [9]. Material and method: This is an analytical retrospective study carried out in a database - Epi-Info resulting from records of Surveillance and Seroprevalence actions in five endemic municipalities for leprosy located in the Southeast and West of Pará. The following variables were analyzed: age, sex, Clinical Classification, vaccination status with BCG, and the result of the search for IgM antibodies against PGL-1 of Mycobacterium leprae by the “In house” ELISA technique. Results: We evaluated 1551 records examined in the laboratory from 2014 to 2016, which were classified into 123 Multibacillary -MB patients (123/1551 = 7.93%); 71 Paucibacillary-PB patients (71/1551 = 4.57%); 451 Intradomicilliary Consanguineous Contacts - CCOSI (451/1551 = 29.07%) and 906 Non Consanguineous Contacts - CNCOS (906/1551 = 58.41%). 57 MB patients (13.47%), 13 PB patients (3.07%), 133 CCOSI (31.44%) and 220 CNCOS (52.00%) were positive for PGL-1. The correlation of the Classification with the vaccination status showed 57 MB patients without any BCG (57/125 = 45.6%) and only 3 patients with two doses of BCG (3/125 = 2.4%); 17 PB patients without any dose of BCG (17/69 = 24.63%); 80 CCOSI without any BCG (80/455 = 17.58%) and 171 CNCOS (171/906 = 18.87%). The odds ratio (OR) in the analysis between unvaccinated MB patients compared to CCOSI was statistically significant (OR = 14.25; p ˂ 0.0001). The study shows the importance of using the BCG vaccine in healthy contacts of patients with leprosy, as it shows the probability of unvaccinated individuals being 14.25 times more likely to become ill with Multibacillary forms compared to CCOSI. In addition, the BCG vaccine has been in use for 80 years and is the only vaccine that we can use in leprosy control programs. Conclusion: Although the leprosy epidemiological data analyzed recently (2010 - 2015) show a downward trend in the main indicators in Pará, such as the detection of new cases and prevalence, the endemic municipalities are still classified as hyperendemic for the population under 15 years of age and This proves that Surveillance is essential, as well as BCG vaccination according to the Ministry of Health Standards.

Evaluation of the integrity of the facial muscles in leprosy patients using surface electromyography: a cross-sectional study

Objective This study sought to evaluate facial muscle integrity in clinical forms of leprosy through surface electromyography. Methods For evaluation of facial muscle integrity, 19 healthy subjects and 71 patients diagnosed with leprosy and under treatment in a National leprosy reference center were recruited. The muscles investigated, through surface electromyography, were the frontalis, orbicularis oculi, zygomaticus, masseter, and orbicularis oris. The evaluated features were Root Mean Square (RMS) and Mean frequency (Fmean). The facial muscles were analyzed jointly and separately for each leprosy clinical form and healthy individuals. Results Regarding the Fmean, there was a difference noted between the values of healthy subjects and patients of all clinical forms, except for the LL form (p = 0.986). The highest frequency values were seen in TT and BL forms, which did not present a significant difference between each other (p = 0.757). Asymmetry of the facial muscles was detected in TT (RMS) and TT, BB, and LL forms from the Fmean. RMS and Fmean indicated motor neurogenic impairment in facial muscles of all leprosy patients, except the LL form. Conclusions Surface electromyography is shown to be an auxiliary tool for the diagnosis of facial motor disorders imperceptible to clinical examination, helping to prevent impairments, which is fundamental for the social inclusion of leprosy patients.

Leprosy Reactions and Neuropathic Pain in Pure Neural Leprosy in a Reference Center in Rio de Janeiro - Brazil.

IntroductionLeprosy reactions are complications that can occur before, during, or after multidrug therapy (MDT) and are considered a major cause of nerve damage. Neuritis is an inflammatory process that causes nerve function impairment associated with pain and tenderness along the nerve. Neuritis can be found in both type 1 and type 2 reactions and may also be the sole manifestation of a leprosy reaction. The objective of this study is to describe the incidence of leprosy reactions and its association with neuropathic pain in pure neural leprosy (PNL) patients.MethodsWe selected 52 patients diagnosed with PNL and 67 patients with other clinical forms of leprosy. During the MDT the patients visited the clinic monthly to take their supervised dose. The patients were instructed to return immediately if any new neurological deficit or skin lesions occurred during or after the MDT.ResultsOf the PNL patients, 23.1% had a leprosy reaction during or after the MDT, while this was 59.7% for patients with the other clinical forms of leprosy. There was an association between having PNL and not having any reaction during and after the MDT, as well as having PNL and having neuritis after the MDT.There was also an association between having previous neuritis and having neuropathic pain in the other clinical forms of leprosy group, although this association was not present in the PNL group.DiscussionOur data suggest that PNL is a different form of the disease, which is immunologically more stable. In addition, PNL patients have more neuritis than the classical leprosy skin reactions. In PNL there was no association between acute neuritis and neuropathic pain, suggesting that these patients may have had silent neuritis. Understanding and identifying neuritis is essential to reduce disability and the impact on public health.

Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects.

BACKGROUND Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation.OBJECTIVES To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects.METHODS The study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed.RESULTS The GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-β1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test.CONCLUSION These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy.

Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load.

Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.

Expression of annexin-A1 in blood and tissue leukocytes of leprosy patients.

INTRODUCTION In leprosy, immune system mediators that regulate the infectious process act in a complex manner and can lead to several clinical outcomes. To understand the behavior of these mediators we quantified the expression of annexin-A1 (ANXA1) in the peripheral blood and plasma as well as tissue leukocytes in all clinical forms of leprosy and compared with healthy controls. METHODS Seventy healthy controls and 70 patients with leprosy, tuberculoid (TT) (n = 13), borderline tuberculoid (BT) (n = 15), borderline borderline (BB) (n = 13), borderline lepromatous (BL) (n = 15), and lepromatous leprosy (LL) (n = 14), were selected. Phenotyping of the lymphocyte cells and the intracellular expression of ANXA1 in leukocytes was performed by immunofluorescence. Plasma protein levels were determined by enzyme-linked immunosorbent assay. RESULTS Histiocytes and CD4+ and CD8+ T cells in the skin of BL and LL patients had higher ANXA1 expression. ANXA1 expression was also high in circulating polymorphonuclear, monocytes, and CD4+ and CD8+ T cells in the blood of LL patients compared to those of TT, BT, BB, and BL patients, and these levels were similar to those in healthy controls. Plasma ANXA1 levels indicate an increase in paracrine release in patients with LL. CONCLUSIONS The data indicate that ANXA1 expression is enhanced in the leukocytes and plasma of patients with LL, and may contribute to the inhibition of leukocyte action, leading to inadequate functioning of the immune system and thus contributing to the spread of M. leprae infection.

Potential for serodiagnosis of Indonesian leprosy patients by detecting antibodies against LID-1

Leprosy is caused by Mycobacterium leprae infection and remains a major public health problem in many areas of the world. The Leprosy IDRI Diagnostic (LID)-1 antigen has demonstrated potential to improve the diagnostic capacity of local health centers and aid the development of strategies for the eventual control and elimination of leprosy from endemic areas. The diagnostic capacity of LID-1 has not yet, however, been studied in Indonesia. Objective: To determine the proportion of Indonesian leprosy patients that have circulating antibodies against LID-1. Sera from thirtyfive leprosy patients from Surabaya, Indonesia were evaluated using an Enzyme Linked Immunosorbent Assay (ELISA) detecting IgG antibodies against the LID-1 antigen. Anti-LID-1 antibody levels correlated with both the clinical form of leprosy and the bacterial index (BI). LID-1-specific IgG responses were higher in multibacillary (MB) than in paucibacillary (PB) leprosy patients. Our data indicate that the detection and measurement of serum IgG against LID-1 could be an effective tool for use in control programs in various states and municipalities in Indonesia.

Evaluation of the cutaneous sensation of the face in patients with different clinical forms of leprosy.

BackgroundLeprosy can be considered to be the most common peripheral neuropathy of infectious etiology and constitutes a public health problem. The standard routine examination for assessing sensory impairment in leprosy neuropathy basically evaluates hands, feet and eyes. However, evaluation of facial cutaneous sensation is not routinely performed.ObjectivesThe aim of this study was to evaluate facial cutaneous sensation in patients with different clinical forms of leprosy and compare the findings with those from healthy individuals.Methodology19 healthy controls and 71 leprosy patients who were being treated at a national reference center for leprosy in Brazil underwent facial sensation assessment using the Semmes-Weinstein monofilament test. This test was applied over the facial areas corresponding to the ophthalmic, maxillary and mandibular distal branches of the trigeminal nerve.ResultsThe predominant clinical form in terms of changes to facial cutaneous sensation was lepromatous leprosy (LL), followed by the borderline-borderline (BB), and borderline-lepromatous (BL) forms, in comparison with healthy individuals. The distal branches most affected were the zygomatic (28.2%; 20/71), buccal (23.9%; 17/71) and nasal (22.5%; 16/71). There was asymmetrical sensory impairment of the face in 62.5% (20/32) of the cases.ConclusionThe face is just as impaired in leprosy as are the feet, hands and eyes, but facial impairment is underdiagnosed. Our evaluation on the different sensory branches and evidence of asymmetrical impairment of the face confirm the classically described pattern of leprosy neuropathy, i.e. consisting of asymmetrical and predominantly sensory peripheral neuropathy.

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.

Protein profile of leprosy patients with plantar ulcers from the Eastern Amazon region

BackgroundStudies investigating the nutritional status of patients with leprosy and plantar ulcers are sparse. Therefore, the objective of this study was to describe the protein profile of leprosy patients with plantar ulcers from the Eastern Amazon region.MethodsA case record form was created for 75 patients with leprosy (31 with plantar ulcers and 44 without plantar ulcers) with the following data: sociodemographic characteristics, clinical form of leprosy, presence or absence of plantar ulcers, and nutritional assessment using anthropometry consisting of the measurement of body mass index, arm circumference, arm muscle circumference, and triceps skinfold. Levels of blood albumin, transferrin, and C-reactive protein (CRP) were also measured. Data regarding protein intake were obtained using a Food Frequency Questionnaire.ResultsPlantar ulcers occurred more frequently in male patients (67.7%), patients aged 40–49 years (mean ± SD: 47.3 ± 8.0 years), and patients receiving 300 or 600 USD (71.0%). The mean weight and height of patients were 71.6 ± 11.4 kg and 1.62 ± 0.1 m, respectively. High levels of CRP were detected in 51.6% of leprosy patients with plantar ulcers and only 9.1% of patients without plantar ulcers (P < 0.001). Nutritional depletion of transferrin was observed in 14.3% of patients with paucibacillary leprosy and 44.3% of patients with multibacillary leprosy (P = 0.0447). Most patients had normal levels of serum albumin (74.2% with plantar ulcers and 77.3% without plantar ulcers).ConclusionsMost leprosy patients with plantar ulcers have normal levels of serum albumin and transferrin and high CRP levels, which indicates the presence of an inflammatory process. Our findings suggest the need to monitor patients with leprosy to prevent the occurrence of plantar ulcers and to provide adequate treatment for patients with existing plantar ulcers.

Analysis of clinical data and T helper 1/T helper 2 responses in patients with different clinical forms of leprosy.

Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.

QPCR detection of Mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms

Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease.

Thermographic analysis and autonomic response in the hands of patients with leprosy.

BackgroundLow temperatures and slow blood flow may result from peripheral neuropathy caused by leprosy, and the simple detection of cold fingers could already be a preliminary classification for these patients.ObjectiveTo investigate whether infrared thermography would be able to measure this change in temperature in the hands of people with leprosy.MethodThe study assessed 17 leprosy patients who were under treatment at the National Reference Center for Sanitary Dermatology and Leprosy, Uberlândia/MG, and 15 people without leprosy for the control group. The infrared camera FLIR A325 and Therma CAM Researcher Professional 2.9 software were used to measure the temperature. The room was air-conditioned, maintaining the temperature at 25°C; the distance between the camera and the limb was 70 cm. The vasomotor reflex of patients was tested by a cold stress on the palm.ResultsThe study showed a significant interaction between the clinical form of leprosy and temperature, where the control group and the borderline-borderline form revealed a higher initial temperature, while borderline-lepromatous and lepromatous leprosy showed a lower temperature. Regarding vasomotor reflex, lepromatous leprosy patients were unable to recover the initial temperature after cold stress, while those with the borderline-tuberculoid form not only recovered but exceeded the initial temperature.ConclusionThermography proved a potential tool to assist in the early detection of neuropathies, helping in the prevention of major nerve damage and the installation of deformities and disabilities that are characteristic of leprosy.

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients.

Leprosy is mainly transmitted among family members who share genetic and ambient factors. The clinical form of leprosy in the index case and kinship could be risk factors for leprosy transmission. High antibody levels in household contacts (HC) in the absence of neural or skin lesions may characterize latent infection. This study aimed to evaluate the association between seropositivity for anti-phenolic glycolipid-I immunoglobulin M antibodies (APGL-I) in HC and the clinical classification of the index case and to analyze the association between APGL-I positivity with other factors such as age, kinship, and gender. We performed a survey among 320 HC of 120 leprosy patients who were evaluated and followed-up in a leprosy outpatient clinic of a university hospital. All HC underwent complete skin examination, peripheral nerve palpation, skin sensory tests, and serologic tests for the detection and quantification of APGL-I. The overall seropositivity rate was 20%, and was greatly affected by kinship. APGL-I seropositivity was higher in siblings (41%), followed by parents (28%), spouses (26%), other (19%), and offspring (14%). Independent risk factors for seropositivity were being siblings (OR 3.3) and being a HC of an index case with indeterminate leprosy (OR 5.3). APGL-I seropositivity was associated with index cases with a bacillary index of 4 (88%; p<.001). Seropositivity among HC was not significantly associated with their gender and age. There was no statistical difference in the seropositivity rates of HC of index patients with paucibacillary and multibacillary leprosy. Strict evaluation and follow-up of HC with positive results for APGL-I is recommended. Special attention should be paid during the screening of siblings of the index cases, HC of patients with a high bacillary index, and HC of patients with indeterminate leprosy.

Clinical features of relapse after multidrug therapy for leprosy in China

Although the World Health Organization (WHO) has defined relapse in leprosy, it is often difficult to confirm a relapse, especially in paucibacillary (PB) patients. To study features of relapse cases in order to determine the information needed to allow better management of relapses in the leprosy control programme. A retrospective survey by questionnaire was carried out at national level at the end of 2012. There were 40 relapsed patients on register. The clinical form of leprosy was TT5, BT4, BB5, BL13 and LL13. Twenty-eight patients had had a positive skin smear test at the start of MDT, with a BI ranging from 0.83 to 6.0. At the time of completing MDT, the skin smear test remained positive in seven patients. After completion of MDT, other family members of 13 patients were identified as new leprosy patients. All relapse cases showed one or more active skin lesions. There were 33 patients with a positive skin smear test at the time of relapse. A total of 23 patients had a biopsy at the time of relapse, including seven patients with a negative skin smear test. The histological features of relapsed BB-LL patients included granulomas containing macrophages or epithelioid cells with sparse lymphocytes and acid-fast bacilli. The histological features of seven patients with negative skin smears showed epithelioid cell granulomas with dense lymphocytes surrounding the granuloma, but without distinct edema in the dermis. The average interval from completion of MDT to the diagnosis of relapse was 168.5 ± 92.6 months with a range of 21-322 months. During the study, nine patients were tested for rifampicin resistance, but none showed any mutation. Leprosy relapse after MDT usually occurred late and all relapse cases had new active skin lesions. Most patients relapsed with a positive skin smear after previously reaching negative BI status. Relapse with a negative skin smear test should be confirmed very cautiously.