Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy

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.

Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy.

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.

Transmission of dapsone-resistant leprosy detected by molecular epidemiological approaches.

Drug resistance surveillance identified six untreated leprosy patients in the Philippines with Mycobacterium leprae folP1 mutations which confer dapsone resistance. Five patients share a village of residence; four who carried the mutation, Thr53Val, were also linked by M. leprae variable-number tandem repeat (VNTR) strain types. In India, folP1 mutations were detected in two relapse patients with a history of dapsone treatment. Mutations were not found in the rifampin target gene rpoB. These findings indicate that dapsone resistance is being transmitted.

Relapse study in smear positive multibacillary (MB) leprosy after 1 year WHO-multi-drug therapy (MDT) in Cebu, Philippines.

OBJECTIVE: To determine the frequency, time interval to relapse and the possible risk factors for relapse in multibacillary (MB) leprosy after 1 year's treatment with the standard multi-drug therapy (MDT). MATERIALS AND METHODS: Smear positive MB patients treated with MDT for 1 year were enrolled in a prospective relapse study between 1999 and 2005 at the Leonard Wood Memorial Center for Leprosy Research (LWM). After treatment completion, at yearly intervals, patients underwent slit-skin smear examination and were clinically monitored for possible signs of relapse. RESULTS: 300 patients were recruited, and by 2009, follow-up totaled 1,913 patient years, with a mean of 6.4 years per patient. Only one case of relapse was detected, with an absolute relapse rate of 0.3% (0.52 per 1000 patient-years at risk (PYAR)); among a subset with pre-treatment bacterial indices (BI) of > or = 4 +, the rate was 0.6%. Relapse occurred 7 years after MDT. CONCLUSION: These data provide strong evidence of the long-term efficacy of the one year WHO-MDT for multibacillary (MB) leprosy patients, even in those with a high initial BI.

Impacts of the diagnosis of leprosy and of visible impairments amongst people affected by leprosy in Cebu, the Philippines.

PURPOSE: To quantify the impact of the diagnosis of leprosy and of visible impairments in people affected by leprosy. SUBJECTS AND METHODS: Three interview-based questionnaires designed to measure activity limitation, participation restriction, and general self-efficacy were used to collect data from three Groups. Group 1: leprosy affected people with visible impairment, Group 2: newly diagnosed leprosy patients with no visible impairment, Group 3: patients with other skin diseases symptomatic for more than 1 month. RESULTS: One hundred and eight subjects were recruited. The subjects with visible impairments (Group 1) had higher levels of participation restriction than those with skin disease (P0.012), and participation restriction was similar between subjects in Groups 2 and 3 (P0-305). The people in Group 1 (35 subjects) also reported significantly more activity limitation compared to the people in either Group 2 (35 subjects) or Group 3 (38 subjects) (P 0-001, respectively). The subjects in Group 2 had no significant activity limitation compared with those in Group 3 (P0.338). A multivariate analysis showed that severe visible impairment was a risk factor for activity limitation (odds ratio 5.68, 95% CI: 1.09-297, P0.039) and a low level of self-efficacy (Odds ratio 6.38, 95% CI: 1.06-38.3, P0-043) among people affected by leprosy. CONCLUSION: Visible impairments affected the activities and attitudes of people affected by leprosy. However, others without visible impairment, had activity limitations, participation restrictions and levels of general self-efficacy that were similar to patients with other skin diseases. Prevention of visible impairments should be considered a key intervention for stigma reduction.