Psychometric assessment of the EMIC Stigma Scale for Brazilians affected by leprosy.

BACKGROUND: The Stigma Scale of the Explanatory Model Interview Catalogue (EMIC-SS) is a useful option to investigate leprosy-related stigma, but its psychometric qualities are unknown in Brazil. This study investigated the factor structure, the convergent and known-groups validity, and the reliability of the EMIC-SS for Brazilians affected by leprosy. METHODOLOGY: The Brazilian Portuguese version of the EMIC-SS was validated in 180 persons affected by leprosy at a Reference Center in Rio de Janeiro. Confirmatory factorial analysis (CFA) and Cronbach alpha were used to assess the EMIC-SS internal consistency. The Construct validity was tested using Spearman Correlation, Kruskal-Wallis, and Mann-Whitney tests comparing with the Participation Scale, Rosenberg Self-esteem Scale, Beck Depression Inventory, and a Sociodemographic Questionnaire. Test-retest reliability was evaluated with intra-class correlation (ICC). MAIN FINDINGS: CFA confirmed the one- and two-dimensional models of the scale after retaining 12 of the 15 EMIC-SS items. The 12-item EMIC-SS was consistent (α = 0.78) and reproducible (ICC = 0.751, 95% Confidence Interval = 0.657-0.822, p < 0.0001). A significant correlation was observed between the EMIC-SS and the other scales confirming convergent validity. The EMIC-SS and its factors were able to differentiate several hypothesized groups (age, change of occupation, monthly family income, communicating others about the disease, and perception of difficulty to follow treatment) confirming the scale known-groups validity, both in its one and two-dimensional models. CONCLUSIONS/SIGNIFICANCE: Our study found support for the construct validity and reliability of the EMIC-SS as a measure of stigma experienced by people affected by leprosy in Brazil. However, future studies are necessary in other samples and populations with stigmatizing conditions to determine the optimal factor structure and to strengthen the indications of the validated scale.

Epidemiological profile and severity of erythema nodosum leprosum in Brazil: a cross-sectional study.

BACKGROUND: Leprosy can cause acute reactions, which may be type 1 (reverse reaction) or type 2 (erythema nodosum leprosum - ENL). ENL has been classified as mild, moderate, or severe. In order to standardize the classification, the Erythema Nodosum Leprosum International Study (ENLIST) Group has developed an objective scale, the ENLIST ENL Severity Scale (EESS), which was the first validated severity scale of ENL in the world. The goal of the study was to describe the sociodemographic and clinical characteristics of patients with ENL attending a tertiary hospital in Piauí, Brazil, classifying them according to the EESS. METHODS: A descriptive cross-sectional observational study was conducted on 26 patients recruited sequentially from May 2017 to February 2018. Their data were statistically analyzed and compared against each other through a structured questionnaire. RESULTS: According to the score obtained in the scale, the patients were divided into two groups: mild ENL and moderate/severe ENL. The extent and number of nodules were related to the severity of the cases, and these data were statistically significant. The majority of the patients were male, between the ages of 31 and 49 years old, with low educational level, and residents in the urban area. CONCLUSIONS: This was the first study to use EESS in Brazil. This scale is easy to apply and allows for the enhancement of treatment protocols. The study also showed a correlation between the number and extension of nodules and the severity of the condition.

The cell fate regulator NUPR1 is induced by Mycobacterium leprae via type I interferon in human leprosy.

The initial interaction between a microbial pathogen and the host immune response influences the outcome of the battle between the host and the foreign invader. Leprosy, caused by the obligate intracellular pathogen Mycobacterium leprae, provides a model to study relevant human immune responses. Previous studies have adopted a targeted approach to investigate host response to M. leprae infection, focusing on the induction of specific molecules and pathways. By measuring the host transcriptome triggered by M. leprae infection of human macrophages, we were able to detect a host gene signature 24-48 hours after infection characterized by specific innate immune pathways involving the cell fate mechanisms autophagy and apoptosis. The top upstream regulator in the M. leprae-induced gene signature was NUPR1, which is found in the M. leprae-induced cell fate pathways. The induction of NUPR1 by M. leprae was dependent on the production of the type I interferon (IFN), IFN-ß. Furthermore, NUPR1 mRNA and protein were upregulated in the skin lesions from patients with the multibacillary form of leprosy. Together, these data indicate that M. leprae induces a cell fate program which includes NUPR1 as part of the host response in the progressive form of leprosy.

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis.

Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single nucleotide polymorphisms (SNPs) in host immune related genes have been consistently suggested as participants in susceptibility towards disease. Interleukin-10 (IL-10) is a crucial immunomodulatory cytokine in mycobacterial pathogenesis and especially the -819C>T SNP (rs1800871) has been tested in several case-control studies indicating association with leprosy risk, although a recent consensus estimate is still missing. In this study, we evaluated the association of the -819C>T SNP and leprosy in two new Brazilian family-based populations. Then, we performed meta-analysis for this polymorphism summarizing published studies including these Brazilian family-based groups. Finally, we also retrieved published studies for other distal and proximal IL10 polymorphisms: -3575 T>A (rs1800890), -2849 G>A (rs6703630), -2763 C>A (rs6693899), -1082 G>A (rs1800896) and -592 C>A (rs1800872). Results from meta-analysis supported a significant susceptibility association for the -819T allele, with pooled Odds Ratio of 1.22 (CI = 1.11-1.34) and P-value = 3x10(-5) confirming previous data. This result remained unaltered after inclusion of the Brazilian family-based groups (OR = 1.2, CI = 1.10-1.31, P-value = 2x10(-5)). Also, meta-analysis confirmed association of -592 A allele and leprosy outcome (OR = 1.24, CI = 1.03-1.50, P-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r(2) = 1.0 between the -592C>A and -819C>T SNPs. We found no evidence of association for the other IL10 polymorphisms analyzed for leprosy outcome. Our results reinforce the role of the -819C>T as a tag SNP (rs1800871) and its association with leprosy susceptibility.

Schwann cells producing matrix metalloproteinases under Mycobacterium leprae stimulation may play a role in the outcome of leprous neuropathy.

Matrix metalloproteinases (MMPs) mediate demyelination and breakdown of the blood-nerve barrier in peripheral neuropathies. Matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 gene expression and secretion were studied in cells of the human Schwann cell line ST88-14 stimulated with Mycobacterium leprae and tumor necrosis factor (TNF) and in nerve biopsies from patients with neural leprosy (n = 21) and nonleprous controls (n = 3). Mycobacterium leprae and TNF induced upregulation of MMP-2 and MMP-9 and increased secretion of these enzymes in cultured ST88-14 cells. The effects of TNF and M. leprae were synergistic, and anti-TNF antibody blockage partially inhibited this synergistic effect. Nerves with inflammatory infiltrates and fibrosis displayed higher TNF, MMP-2, and MMP-9 mRNA than controls. Leprous nerve biopsies with no inflammatory alterations also exhibited higher MMP-2 and MMP-9; tissue inhibitor of metalloproteinase 1 was significantly higher in biopsies with fibrosis and inflammation. Immunohistochemical double labeling of the nerves demonstrated that the MMPs were mainly expressed by macrophages and Schwann cells. The biopsies with endoneurial inflammatory infiltrates and epithelioid granulomas had the highest levels of MMP-2 and MMP-9 mRNA detected. Together, these results suggest that M. leprae and TNF may directly induce Schwann cells to upregulate and secrete MMPs regardless of the extent of inflammation in leprous neuropathy.

Leprosy reaction as a manifestation of immune reconstitution inflammatory syndrome: a case series of a Brazilian cohort.

Several case reports have demonstrated that the immune reconstitution inflammatory syndrome induces reversal reaction in HIV and leprosy-coinfected patients. The present study describes 10 cases of immune reconstitution inflammatory-associated reversal reaction. The patients evolved satisfactorily despite presenting a more severe form of the disease and the fact that three required an additional use of corticoids. The present study, the largest case series published to date, demonstrates that leprosy reaction is a manifestation of immune reconstitution.

[Hansen's disease in the laboratory]. / A hanseniase no laboratório.

A physical doctor with a PhD in Pathology, Euzenir Nunes Sarno studies the immunology factors of Hansen's disease, one of the oldest chronic infections and that is an exclusively human disease. Staff member of an ambulatory that has become a reference on the disease in Brazil with 220 to 250 new patients per year, Euzenir emphasizes that the fact one cannot cultivate Mycobacterium leprae brings about some everlasting questions in relation to the transmission of and the sensitivity to the disease. There are also many epidemiology questions that remain unanswered. Estimates show that, among those who have contact with multi-bacilli patients, 90% are infected but only about 8% get sick. The high infection rate of those who live with multi-bacilli patients but never fall sick shows that just a small number of individuals are sensitive to Mycobacterium leprae. This is one of the questions immunology has not been able to answer. Why do some people resist to it and some don't? The figures are even lower when compared to those who are in contact with patients that are paucibacillus-infected, i.e. a manifestation of the disease with few bacilli. Hansen's disease is known as a skin malady. But, according to the specialist, its first damage is to the nerve, when the area becomes insensitive. Besides damaging the sensitive skin nerves, the disease can lead to motor disability and irreversible deformities, which sometimes lead to the amputation of limbs and protruded parts of the body. Mycobacterium leprae was one of the first pathogenic bacteria whose genome sequence has been entirely mapped. Only now we have the capacity to have more precise assessments. The disease is not inherited, and only in 1986 health services in Brazil began to take the responsibility for both the disease and its patients. During the twenty-year military dictatorship the country underwent, the health system was dismantled. In 1991, the one-year treatment with three drugs - Dapsone, Rifanpicine and Clofazimine- was introduced in our country. Just 30% of the cases get to negative results after the treatment. according to the interviewee, whereas tuberculosis is a highly virulent multi-bacilli disease, leprosy bacillus is not virulent, is a 'lazy' germ at the end of its evolutional process. One third of its genome does not work.