Association of MICA and HLA­B alleles with leprosy in two endemic populations in Brazil

Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case­control and a family­based study in two endemic populations in Brazil. MICA and HLA­B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR­SSOP­Luminex­based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi­square or Fisher's exact test together with a multivariate analysis. Family­based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002­HLA­B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA­A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA­B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA­B markers rs2596498 and rs2507992, and high LD (R2 = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA­B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele(AU).

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme

Background: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. Methods The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. Findings Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. Interpretation Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established(AU).

Neurophysiological comparative response to clinical and surgical treatment of the ulnar neuropathy in leprosy / Padrões neurofisiológicos da resposta tardia ao tratamento clínico e cirúrgico da neuropatia ulnar na hanseníase

Leprosy neuropathy may develop into subacute and chronic inflammatory scenarios, called reactions, which may cause entrapments in the anatomic tunnels. Objective: This study describes the late nerve conduction findings in patients with ulnar neuropathy at the elbow that were submitted to clinical and surgery treatments. Methods: A total of 27 nerves of 21 patients with borderline leprosy during type 1 (reversal) reaction were selected in a non- competing retrospective cohort for three years. The nerves with treated clinically active neuropathy (Group A1) were randomized for inclusion of surgical treatment (Group A2) after one month of clinical treatment without clear signs of clinical and neurophysiological improvement. Fifteen nerves were randomly chosen for surgery while 12 were clinically treated, after steroids treatment without expected response. Nerve conduction was measured before and after treatment on four occasions. Results: The authors observed significant improvement in the following variables in the surgically treated nerves: compound motor action potential amplitude (CMAP) at elbow and above elbow and conduction velocity (CV) along the forearm. Conclusion: The improvement of CMAP amplitudes and conduction velocity (CV) along the forearm express the late effect of nerve decompression. Persistence of temporal dispersion (TD) along the elbow was related to the new reaction or to incomplete surgical solution. However, moderate reduction in CV along the elbow, without TD, was considered an indication of na expected partial remyelination. Previous gradation of the nerve lesion based on the CMAP amplitude was related to the most severe results

A neuropatia de hanseníase pode desenvolver quadros inflamatórios subagudos e crônicos denominados reações, os quais podem evoluir para compressões nos túneis anatômicos. Objetivo: Descrever os achados de condução nervosa (CN) tardios em pacientes com neuropatia ulnar no cotovelo submetidos aos tratamentos clínico e cirúrgico. Método: Vinte e sete nervos de 21 pacientes foram selecionados em uma coorte retrospectiva não-concorrente por um a três anos, sendo formados dois grupos. Após o tratamento clínico sem sinais inequívocos de melhora os nervos foram randomizados para manter o tratamento clinico (Grupo A1) ou adicionar a descompressão do nervo (Grupo A2). Resultados: Os autores observaram melhora significativa nas seguintes variáveis no Grupo A2, tratado com a adição da descompressão cirúrgica, amplitude do potencial de ação motor composto (PAMC) no cotovelo e acima do cotovelo e velocidade de condução (VC) ao longo do antebraço. Conclusão: O ganho em amplitudes dos PAMCs no cotovelo e acima do cotovelo e da velocidade de condução (VC) ao longo do antebraço são a expressão do efeito tardio da descompressão do nervo ulnar. A persistência de dispersão temporal (DT) através do cotovelo foi relacionada a nova reação ou solução cirúrgica incompleta. Entretanto, a persistência de redução moderada da VC através do cotovelo sem a DT foi discutida e considerada como remielinização parcial esperada. A graduação previa da lesão do nervo baseada na amplitude dos PAMCs apresentou relação direta aos resultados menos favoráveis