Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, ...arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with "severe" ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies.
Cebu has been one of the most leprosy endemic areas in the Philippines. Despite the high coverage rates of multiple drug therapy (MDT) and high BCG-vaccine coverage in children, leprosy control ...authorities believe that leprosy transmission and incidence (as evidence by continuing new case detection in both adults and children) have not declined as expected, once leprosy had been eliminated. In response to the concerns communicated by the authorities regarding ongoing leprosy transmission in Cebu, this study aims to examine the evidence for the hypothesized ongoing transmission, both in children and adults. Furthermore, it will be assessed which groups and areas are experiencing a continuing risk of leprosy infection; this can form a starting point for more targeted approaches to leprosy control.
Case records from 2000-2010 were retrospectively collected from the Leonard Wood Memorial Clinic archives, and all other clinics on the island where leprosy was treated. Between 2000 and 2010, 3288 leprosy cases were detected. The overall five year case notification rate (CNR) dropped significantly from 47.35 (2001-2005) to 29.21 cases (2006-2010) per 100.000 population. Smaller CNRs were reported for children; however the decline in child-CNR over the same period was minimal. Furthermore, no increase in median age of notification in children or adults was found between 2000 and 2010. Population-adjusted clustering of leprosy cases was mainly detected in urban and peri-urban areas.
Although the overall CNR declined significantly, CNR seems to be rather static in lower risk populations and areas. Cases are mainly found in urban areas, however CNRs in these areas decline at a much faster rate than in the lower endemic rural areas. A similar situation was found when comparing adults and children: CNRs observed in children were lower than in adults, but further decline (and elimination) of these childhood CNRs was found to be difficult. Moreover, the median age of notification in children has remained stable, suggesting transmission is still on-going. It is unclear why many years of good MDT-coverage and a gradual decline in CNR have not been accompanied by evidence of reduced transmission, especially beyond a certain threshold level of case notification. We believe that a new approach to leprosy control is required to tackle transmission more directly. The most promising approach may involve chemoprophylaxis and/or immunoprophylaxis interventions, targeted at high risk (urban) areas and groups such as household contacts, followed by a different approach once decline in CNR starts to level off. Identified clusters and trends can form the starting point for implementing this approach.
Background Diagnosis of leprosy currently requires individuals suspecting themselves to be affected to present for expert clinical exams. Clinic attendance can be impacted by a variety of logistical ...and psychological factors, but rapid diagnostic tests (RDT) could potentially be used as a screening tool to provide triaged referrals. Methods In 2015, 200 newly diagnosed, predominantly multibacillary (MB), leprosy patients attending Cebu Skin Clinic, Philippines, were interviewed with regard to their perception of how leprosy had impacted their lives and their level of acceptance of an immunologic, lateral flow-based RDT as a tool for leprosy control. Six hundred household contacts (HC) of some index cases were also asked to respond to a questionnaire. Each participant provided responses from multiple choice options and the same surveys were repeated on a regular basis to a sub-set of the cohort over the ensuing 4 years. Results At the time of diagnosis many patients (73.0%) and their HC (66.5%) reported that their lives had already been adversely affected by leprosy. RDT were perceived positively by both groups with the majority (87% patients and 71% HC) considering the tool as 'very important'. No patients, and only 0.8% HHC, considered that tests would be of no benefit. In general, patients preferred an extensive RDT monitoring schedule following their diagnosis and indicated a preference that testing be confined among HHC rather than being extended to their larger community. Annual follow-up of a sub-set of participants (131 patients and 170 HC) indicated a retained enthusiasm for testing and, importantly, a marked decrease in those that would not like testing among community contacts, with an increase from 58.5% to 89.4% indicating that they would like testing among their respective HC. Importantly, the perceived impact of leprosy on the lives of both patients and HC declined during the monitoring period that occurred concomitantly with a progressive increase in the number of HC stating that they would definitely submit to testing. Conclusion Our data demonstrate an enthusiasm for regular use of RDT among these particular patients and their HC.Due to their ease of use and point of care applicability RDT could be accepted within high-risk target populations to provide an entry point to inform the early detection of leprosy. Keywords: Leprosy, diagnosis, mycobacteria, beliefs
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.
To quantify the impact of the diagnosis of leprosy and of visible impairments in people affected by leprosy.
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.
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.
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.
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. Keywords: Clofazimine, ENL, type 2 reaction, adverse effects, steroid-sparing, guidelines
Despite control efforts, leprosy persists as a significant health concern in many regions. Diagnosis is achieved by a combination of clinical, histopathological, and bacteriological examinations, ...each of which presents a barrier to expeditious diagnosis, particularly by non-experts. Immunological investigations in research laboratories have clearly indicated that antibody detection tests could aid the diagnosis of leprosy. In this study, we detected circulating antibodies with two rapid diagnostic tests (RDT) involving immunochromatographic lateral flow platforms and one rapid ELISA system. Leprosy patients were identified with a high degree of sensitivity in each assay (over 80 % in all; over 90 % among cases with bacterial indices >1+), although critical differences were observed in specificity. While the specificity of CTK OnSite Leprosy Ab Rapid Test and InBios Leprosy Detect™ fast ELISA were high (96.4 and 93.7 % in the general population, respectively), there was a marked reduction in OrangeLife NDO-LID® RDT (only 25.0 %). As anticipated, seropositivity rates were marginally higher in contacts of leprosy patients than in endemic controls. Although we observed a slight drop in test band intensity when blood, rather than serum, was used to develop OnSite Leprosy Ab Rapid Tests, the sensitivity and specificity of these tests was unaffected. When we contrasted test performance with clinical and bacteriological information, we found that RDT and ELISA results positively correlated with the bacteriological index. These data indicate that these assays could be a ready replacement of invasive, insensitive, and time consuming skin slit smear procedures that additionally require expert microscopic examinations. We propose that, due to their speed and point of care applicability, the RDT could be used as an initial entry point to the diagnostic protocols, with confirmation of results attained in a highly quantitative manner following serum transfer to a reference laboratory.
PDF
