No abstract

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.

BACKGROUNDS -ultibacillary patients are the major source of infection in leprosy. Nevertheless, the risk is higher in household contacts between multibacillary patients than paucibacillary patients and in the general population. Household contacts are in close genetic relationship with the index case-patient. OBJECTIVE: To evaluate epidemiological data of the following variables: age, gender, education level, genetic proximity, and type of contact with the index case-patient (household or not) in 107 families with leprosy. METHODS: Home visits were conducted to clinically examine family members. The medical charts of index case-patients and co-prevalent cases were reviewed. RESULTS: The controlled analysis of variables such as type of contact and genetic proximity revealed that household contacts and first-degree kinship are independently associated with a higher chance of contracting the disease. CONCLUSION: Household contacts are often genetically closer to the index case-patient. To investigate the independent relevance of these risks in leprosy surveillance contact studies has been a challenge. Our results confirm literature data that show the influence of genetics in the susceptibility to leprosy per se. Keywords: Epidemiology; Genetics; Leprosy; Leprosy/epidemiology Resumo: FUNDAMENTOS -Os pacientes multibacilares (MB) são a principal fonte de infecção na hanseníase e esse risco é maior nos contatos domiciliares dos pacientes MB do que nos contatos dos paucibacilares (PB) e na população em geral. Entretanto, os contatos domiciliares são os mais próximos do caso-índice (CI), em termos genéticos. OBJETIVO: Analisar dados epidemiológicos das variáveis: sexo, idade, anos de estudo, grau de parentesco com o CI e tipo de contato residencial (intradomiciliar ou peridomiciliar) com o CI em 107 famílias de hanseníase. MÉTODOS: Foram realizadas visitas domiciliares para exame clínico dos familiares. Os prontuários dos CIs e de seus coprevalentes (contatos familiares que também tiveram hanseníase) foram revistos. RESULTADOS: A análise controlada das variáveis tipo de contato e grau de parentesco revelou que o contato domiciliar e o parentesco de primeiro grau estão independentemente associados a uma probabilidade maior de adoecer. CONCLUSÃO: Os contatos domiciliares, em geral, são os mais próximos do caso, em termos genéticos, e aferir a magnitude desses riscos separadamente tem sido um desafio nos estudos de vigilância de contatos em hanseníase. Os resultados deste estudo confirmam os dados da literatura, demonstrando a influência genética no desfecho da hanseníase per se.

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 r2 = 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.

Treatment with antithyroid drugs may be accompanied by side effects. We present a patient diagnosed with Grave's Disease who developed extensive vasculitis in the lower limbs during methimazole use. After suspension of the methimazole and the introduction of prednisone in immunesupressor doses the cutaneous lesions started to involute.