Emergence and Transmission of Drug-/Multidrug-resistant Mycobacterium leprae in a Former Leprosy Colony in the Brazilian Amazon.

BACKGROUND: Leprosy has been treated with multidrug therapy, which has been distributed for free across the globe and regarded as highly efficient. However, the impossibility of growing Mycobacterium leprae in axenic media has historically impaired assessments of M. leprae resistance, a parameter only recently detectable through molecular methods. METHODS: A systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyperendemic, former leprosy colony located in the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB, and gyrA. A molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR). RESULTS: Mycobacterium leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new cases): 16 (43.24%) displayed drug-resistance variants. Multidrug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in 1 new case. Resistance to dapsone was present in 2 relapses and 1 new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae. CONCLUSIONS: A comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of the emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.

Eritema polimorfo hansênico ulcerado AB initio: uma apresentação atípica de hanseníase na faixa virchowiana / AB initio ulcerated erythema multiforme like type 2 reaction: an atypical presentation of leprosy in the lepromatous range

Paciente masculino, caucasiano, 49 anos, procedente do interior do estado de São Paulo, referiu estar em tratamento de hanseníase multibacilar há 2 meses, e que sua doença foi descoberta por meio de baciloscopia e biópsia de pele. Relatou que há 2 anos notou alteração de sensibilidade na parte distal lateral do pé esquerdo, associada a máculas eritematosas e hipocrômicas hipoestésicas no mesmo membro. Evoluiu com linfonodomegalia axilar e inguinal, placas eritematosas anulares bem delimitadas, disseminadas e dolorosas, algumas com ulceração central, além de nódulos dolorosos em membros, febre alta e mal estar geral. Internado em hospital geral, recebeu antibioticoterapia empírica, sem melhora do quadro, sendo então encaminhado para um infectologista que fez o diagnóstico de hanseníase na faixa virchowiana em reação. Iniciou tratamento com PQT-MB e prednisona, com melhora parcial das lesões, porém com desencadeamento de diabetes mellitus pelo corticoesteróide, e foi encaminhado para o Instituto Lauro de Souza Lima (ILSL). Na admissão, ao exame físico, além das placas, nódulos e discreta linfonodomegalia inguinal e axilar, o paciente não apresentava os sinais clássicos de hanseníase virchowiana, como infiltração difusa, madarose, desabamento nasal, perda de sensibilidade protetora em membros ou espessamento de nervos consistentes. O exame histopatológico do bordo de uma placa mostrou quadro de hanseníase na faixa virchowiana e reação Tipo 2 no derma superficial (eritema polimorfo hansênico), baciloscopia de 5+ (bacilos granulosos). A baciloscopia de pontos índices foi positiva em 6 pontos, 3 a 4 +, bacilos granulosos. A dosagem de IgM anti-PGL-1 (glicolipídeo fenólico 1) por ELISA foi de 0,241 e o teste ML-Flow (teste de fluxo lateral para o M. leprae) foi de 4+. O hemograma mostrou anemia importante (Ht=25%) e leucocitose com desvio a esquerda e granulações tóxicas, VHS 101mm. O exame bacteriológico colhido de uma lesão ulcerada revelou S. aureus coagulase...

A 49 years old white man comes from a city of the inner part of the state of São Paulo with the diagnosis of multibacillary leprosy under treatment for 2 months. He reported that 2 years before he noted loss of sensitivity on his left foot which was associated with several red and hypopigmented macules with disturbance of skin sensitivity. The disease evolved with axillary and inguinal lymphadenopathy, as well as tender sharp borders’ plaques and ill-defined nodules, some of then ulcerated, and high degree fever also occurred. He was then admitted into a general hospital, and empirical antibiotics were started, without improvement of symptoms. An evaluation by an infectologist was requested, and the diagnosis of reactional multibacillary leprosy was made after skin smears and skin biopsy were performed. Multibacillary multidrug therapy (MDT-MB) was started, as well as prednisone, with clinical improvement, but diabetes mellitus induced by prednisone occurred, and the patient was referred to the “Instituto Lauro de souza Lima” (ILSL). At admission, on the physical examination, other than the plaques, nodules and mild inguinal and axillary lymphadenopathy, the patient did not present classical findings of lepromatous leprosy, i.e., madarosis, difuse infiltration of skin, saddle nose, well-defined enlargement of periferal nerve trunks or even important disturbance of sensitivity on his limbs. Histopathologic examination of a skin biopsy collected from the border of a plaque showed leprosy on the lepromatous range with Type 2 reation, and the infiltrate was distributed mainly in the superficial dermis (erythema multiforme-like ENL), bacilloscopy 5+ (fragmented bacilli). Bacilloscopy of skin smears collected from index points was positive in all the 6 points, showing 3-4 +, with fragmented bacilli. ELISA for IgM anti-PGL-1 (phenolic glycolipid-1) was 0,241 and ML-Flow test (lateral flux test for M. leprae) was 4+. Hemogram showed severe anemia (Ht=26%)...