BackgroundThe clinical management of leprosy Type 1 (T1R) and Type 2 (T2R) reactions pose challenges mainly because they can cause severe nerve injury and disability. No laboratory test or marker is available for the diagnosis or prognosis of leprosy reactions. This study simultaneously screened plasma factors to identify circulating biomarkers associated with leprosy T1R and T2R among patients recruited in Goiania, Central Brazil.MethodsA nested case-control study evaluated T1R (n = 10) and TR2 (n = 10) compared to leprosy patients without reactions (n = 29), matched by sex and age-group (+/- 5 years) and histopathological classification. Multiplex bead based technique provided profiles of 27 plasma factors including 16 pro inflammatory cytokines: tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), interleukin (IL)- IL12p70, IL2, IL17, IL1 β, IL6, IL15, IL5, IL8, macrophage inflammatory protein (MIP)-1 alpha (MIP1α), 1 beta (MIP1β), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractrant protein 1 (MCP1), CC-chemokine 11 (CCL11/Eotaxin), CXC-chemokine 10 (CXCL10/IP10); 4 anti inflammatory interleukins: IL4, IL10, IL13, IL1Rα and 7 growth factors: IL7, IL9, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF).ResultsElevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction. IL6 (p = 0.05), IL7 (p = 0.039), and PDGF-BB (p = 0.041) were elevated in T2R. RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples.ConclusionPotential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2. Additional studies on these biomarkers may help understand the immunopathologic mechanisms of leprosy reactions and indicate their usefulness for the diagnosis and for the clinical management of these events.

To detect areas with increased case-detection rates, we used spatial scan statistics to identify 5 of 10 clusters of leprosy in the Amazon region of Brazil. Despite increasing economic development, population growth, and road infrastructure, leprosy is endemic to this region, which is a source of case exportation to other parts of Brazil.

6; IC95%: 3,5;7,7) em comparação aos homens (AAPC = 3,0; IC95%: 0,5;5,6) 5;9; 0,0), comparados às mulheres 4;7;1). A proporção de casos em abandono de tratamento no período foi de 5,5%, com tendência de redução mais significativa entre mulheres 9;7; -1,1) do que em homens 7;4;0). Recidiva foi verificada em 3,8% de todas as entradas do período; as mulheres apresentaram tendência de redução significativa 2;3;0) e os homens, de crescimento significativo (AAPC = 4,9; IC95%: 2,9;6,8 . A proporção de cura na coorte 2003-2014 foi de 85%, com tendência de redução mais acentuada nos homens Hanseníase; Estudos de Séries Temporais; Gênero e SaúdeEste é um artigo publicado em acesso aberto (Open Access) sob a licença Creative Commons Attribution, que permite uso, distribuição e reprodução em qualquer meio, sem restrições, desde que o trabalho original seja corretamente citado.Souza EA et al.

Leprosy is a neglected cause of death in Brazil since the disease is preventable, and a cost-effective treatment is available. Sustainable control measures should include appropriate management and systematic monitoring of leprosy-related complications, such as severe leprosy reactions and adverse effects to multidrug therapy.

Serology using a species-specific antigen for Mycobacterium leprae, PGL-I, could be a marker for the bacterial load of patients with leprosy. Various studies have identified the potential use of serology in the classification of patients for treatment purposes, case monitoring, identification of the risk of relapse and selection of household contacts with a higher risk of contracting the disease. A systematic review of the literature was conducted and 26 articles were included in this comparative analysis. The results of the use of PGL-I serology in different situations, its limitations and possible applications were evaluated. Studies show the efficacy of PGL-I serology in the classification of patients, treatment monitoring and as a predictive test for leprosy reactions. To improve early diagnosis and follow-up of the population at greatest risk of developing leprosy, the methodologies used in the past have yet to show a favorable cost-benefit ratio, although studies indicate that the use of the test might positively influence leprosy control programs. With simple and robust techniques, the use of PGL-I serology is viable.

h Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P ‫؍‬ 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary. There is no doubt about the efficiency of the currently used multidrug therapy (MDT) scheme for treatment of leprosy, as demonstrated by the strong decrease in disease prevalence since its implementation and the low number of reported relapse cases (18). However, there has been a scarcity of in-depth studies of relapse occurrences in recent decades (27). As is known, differentiating diagnosis of relapse and reactional states poses some difficulties in the field, being responsible for under-or overdiagnosis of both disease stages. This is important because undiagnosed relapse cases could contribute to continuing disease transmission. In addition, hardly any data on the contribution of emergence of drug-resistant strains of Mycobacterium leprae to leprosy relapses exist.Diaminodiphenylsulfone (DDS), also called dapsone, was the first drug to be effective against leprosy worldwide, and the first cases of resistance to dapsone were detected in 1964 and involved two single nucleotide polymorphisms (SNPs) in the gene folP1, located in codons 53 and 55 (8, 9, 14, 29). Rifampin is the key component of the standard multidrug regimen used for treatment of leprosy, and it has been shown that PCR-based DNA sequence analysis of the rpoB gene of M. leprae was in full concordance with rifampin susceptibility testing in the mouse footpad system (17, 30). In addition to dapsone and rifampin, ofloxacin is also used for leprosy treatment and is a quinolone with an action mechanism based on interaction with DNA gyrase (2); SNPs in gyrA and gyrB confer resistance or hypersensitivity to quinolones (15). Although there is not yet an official definition of multidrug resistance (MDR) in leprosy, in parallel with tuberculosis, we adopt this terminology when we encounter resistance to rifampin and one other drug of the standard M...

Resumo: FUNDAMENTOS -A hanseníase é doença infectocontagiosa crônica causada pelo Micobacterium leprae. Caracteriza-se por acometimento dermatoneurológico, variando em espectro entre dois pólos estáveis. Apesar de curável, ainda representa relevante problema de saúde pública, sendo o Brasil o segundo país mais endêmico do mundo. Sua maior morbidade associa-se aos estados reacionais e ao acometimento neural, podendo causar incapacidades físicas permanentes que comprometem significativamente a qualidade de vida dos pacientes, com auto-estigmatização e vergonha. OBJETIVO -Avaliar o grau de comprometimento da qualidade de vida nos pacientes com hanseníase. MÉTODOS -Estudo observacional com correlação entre variáveis clínicas de gravidade da doença e questionário de avaliação da qualidade de vida: Dermatology Life Quality Index. RESULTADOS -Dos 40 pacientes avaliados, a maioria apresentou comprometimento da qualidade de vida de grave a muito grave segundo score obtido no Dermatology Life Quality Index. As variáveis analisadas individualmente também mostraram correlação de gravidade com o número de pontos obtido. CONCLUSÃO -A hanseníase causa sofrimento que ultrapassa a dor e o mal-estar estritamente vinculados ao prejuízo físico, com grande impacto social e psicológico, justificando tanto avanços para abordagem multidisciplinar ao paciente quanto a necessidade de ações de saúde que visem ao controle da doença. Palavras-chave: Doenças endêmicas; Hanseníase; Qualidade de vida; Questionários Abstract: BACKGROUND -Hansen's disease is a chronic infecto-contagious illness caused by

Leprosy is an infectious disease caused by Mycobacterium leprae. Tumor necrosis factor (TNF) plays a key role in the host response. Some association studies have implicated the single nucleotide polymorphism TNF -308G>A in leprosy susceptibility, but these results are still controversial. We first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308A allele (odds ratio [OR] = 0.77; P = .005). Next, results of a meta-analysis reinforced this association after inclusion of our new data (OR = 0.74; P = .04). Furthermore, a subgroup analysis including only Brazilian studies suggested that the association is specific to this population (OR = 0.63; P = .005). Finally, functional analyses using whole blood cultures showed that patients carrying the -308A allele produced higher TNF levels after lipopolysaccharide (LPS) (6 hours) and M. leprae (3 hours) stimulation. These results reinforce the association between TNF and leprosy and suggest the -308A allele as a marker of disease resistance, especially among Brazilians.