Multidrug therapy for leprosy can cure patients with lobomycosis in Acre State, Brazil: a proof of therapy study

Lobomycosis, also referred to as lacaziosis, is an endemic cutaneous and subcutaneous fungal disease that mainly affects Amazonian forest dwellers in Brazil. There is no disease control program in place in Brazil, and antifungal therapy failures are common, and the therapy is inaccessible to most patients. We performed a randomized, unblinded clinical trial testing the cure rate of multiple drug therapy (MDT) for leprosy with surgical excision, with or without itraconazole. A control arm consisted of patients who did not adhere to either therapeutic regimens but continued to be followed up. Multiple drug therapy consisted of monthly supervised doses of 600 mg rifampicin, 300 mg clofazimine, and 100 mg dapsone, in addition to daily doses of 50 mg clofazimine and 100 mg dapsone. The patients in the MDT plus itraconazole arm also received itraconazole 100 mg twice daily. We followed up 54 patients from the MDT group and 26 patients from the MDT plus itraconazole group for an average of 4 years and 9 months. The 23 controls were followed up for 6 months on average. The following endpoints were observed: 1) unchanged (no apparent improvement), 2) improved (reduction in lesion size and/or pruritus), and 3) cured (complete remission of the lesions, no viable fungi, and no relapse for 2 years after the end of the drug treatment). The results indicated a significantly greater likelihood of cure associated with the use of multidrug therapy for leprosy with or without itraconazole when compared with the control group. The addition of itraconazole to MDT was not associated with improved outcomes, suggesting that MDT alone is effective(AU).

Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Previous studies have demonstrated that the difference among clinical forms of leprosy can be associated with the immune response of patients, mainly by T helper (Th) and regulatory T cells (Tregs). Then, aiming at clarifying the immune response, the expression of cytokines related to Th1, Th2, Th17 and Tregs profiles were evaluated by qPCR in 87 skin biopsies from leprosy patients. Additionally, cytokines and anti-PGL-1 antibodies were determined in serum by ELISA. The results showed that the expression of various targets (mRNA) related to Th1, Th2, Th17 and Tregs were significantly modulated in leprosy when compared with healthy individuals, suggesting the presence of a mixed profile. In addition, the targets related to Th1 predominated in the tuberculoid pole and side and Th2 and Tregs predominated in the lepromatous pole and side; however, Th17 targets showed a mixed profile. Concerning reactional events, Tregs markers were decreased and IL-15 was increased in reversal reaction and IL-17F, CCL20 and IL-8 in erythema nodosum leprosum, when compared with the respective non-reactional leprosy patients. Additionally, ELISA analysis demonstrated that IL-22, IL-6, IL-10 and anti-PGL-1 antibody levels were significantly higher in the serum of patients when compared with healthy individuals, and IL-10 and anti-PGL-1 antibodies were also increased in the lepromatous pole and side. Together, these results indicate that Th1, Th2 and Th17 are involved in the determination of clinical forms of leprosy and suggest that decreased Tregs activity may be involved in the pathogenesis of reactional events.

Recidivas associadas à resistência a drogas na hanseníase / Relapse related to drug resistance in leprosy

A poliquimioterapia/Organização Mundial da Saúde foi implantada efetivamente no Brasil em 1991, contribuindo drasticamente para redução da taxa de prevalência e cura da hanseníase. No entanto, a sua comprovada eficácia não tem impedido a ocorrência de recidiva da doença. Falha no tratamento, persistência bacilar ou resistência a drogas são fatores que podem ou não estarem associados a ela. O objetivo deste estudo foi verificar a ocorrência de recidiva e associá-la com a presença de cepas resistentes do Mycobacterium leprae entre 28 indivíduos que apresentaram suspeita clínica de recidiva após tratamento por monoterapia sulfônica, esquema da Divisão Nacional de Dermatologia Sanitária ou poliquimioterapia. Biópsias das lesões de pacientes multibacilares, com diagnóstico clínico de recidiva, atendidos por demanda espontânea, foram coletadas para avaliar resistência a drogas por meio da técnica de inoculação em pata de camundongo. Dentre as amostras avaliadas 42,8% apresentaram bacilos sensíveis à dapsona e rifampicina e 10,7% apresentaram resistência à dapsona; não foram isolados bacilos resistentes à rifampicina. A emergência de bacilos resistentes, especialmente à rifampicina, é um alerta para os programas de controle da hanseníase. Monitorar a disseminação destas cepas é importante, pois elas apresentam um sério obstáculo para a eliminação da doença, principalmente em países onde a hanseníase ainda é endêmica.

The multidrugtherapy proposed by the World Health Organization has been effectively implemented in Brazil in 1991. It helped reduce the prevalence and achieve the cure of leprosy. However, its proven efficacy has not prevented the occurrence of relapses in some leprosy patients. Irregular treatment, bacillary persistence or resistance of Mycobacterium leprae to drugs are factors that may be associated with relapse. The objective of this study was assess the occurrence of relapse and associate it with the presence of Mycobacterium leprae resistant strains. In order to do that, 28 individuals who were clinically diagnosed as relapse after treatment with sulphone monotherapy, the National Division of Sanitary Dermatology scheme or multidrugtherapy. Biopsies from lesions of multibacillary patients attended by spontaneous demand were collected to verify resistance to drugs through the mouse foot pad inoculation technique. Among the samples evaluated 42.8% had bacilli susceptible to dapsone and rifampicin and 10.7% showed resistance to dapsone. No rifampicin resistant bacilli were isolated. The emergence of resistant strains, especially to rifampicin, is a threat to leprosy control programs, therefore, monitoring the spread of these strains is important because resistance pose a serious obstacle to the elimination of disease, particularly in countries where the disease is endemic.