ABSTRACT
A parte de ser un principio activo de la multiterapia (MDT) para la lepra, la clofazimina a mayores dosis se administra para tratar las reacciones de Tipo 2 (ENL) de la lepra. Todavía falta evidencia en los ensayos clínicos sobre las indicaciones, pauta óptima y ratio riesgo/beneficio para apoyar las directrices publicadas sobre su uso como medicamento antileprorreacción. La experiencia clínica indica que, en adultos, la dosis más alta (de 300 mg/ día) es segura durante períodos limitados de tiempo, pero se necesita precaución en individuos de poco peso corporal y en aquellos en tratamiento con otros medicamentos que puedan interaccionar. (AU)
Besides its role in multidrug therapy, clofazimine at higher doses is widely used for relief of Type 2 (ENL) reaction in leprosy. There is a lack of evidence from clinical trials regarding indications, optimum regimen and risk/benefit ratio to support published guidelines on its use as an anti-reaction drug. Clinical experience suggests that in adults it is safe at high doses (up to 300 mg/day) for limited periods of time but caution is needed with patients of low body weight and in those taking other drugs which may interact. (AU)
Subject(s)
Humans , Clofazimine/adverse effects , Clofazimine/administration & dosage , Leprosy , Guidelines as TopicABSTRACT
Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment efficacy in LPs and assess disease progression in those most at risk for developing this disease.