Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia.

BACKGROUND: Erythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL. METHODS AND RESULTS: Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin. CONCLUSIONS: This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients' assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid-sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale

A leprosy clinical severity scale for erythema nodosum leprosum: An international, multicentre validation study of the ENLIST ENL Severity Scale.

OBJECTIVES: We wished to validate our recently devised 16-item ENLIST ENL Severity Scale, a clinical tool for measuring the severity of the serious leprosy associated complication of erythema nodosum leprosum (ENL). We also wished to assess the responsiveness of the ENLIST ENL Severity Scale in detecting clinical change in patients with ENL. METHODS: Participants, recruited from seven centres in six leprosy endemic countries, were assessed using the ENLIST ENL Severity Scale by two researchers, one of whom categorised the severity of ENL. At a subsequent visit a further assessment using the scale was made and both participant and physician rated the change in ENL using the subjective categories of "Much better", "somewhat better", "somewhat worse" and "much worse" compared with "No change" or "about the same". RESULTS: 447 participants were assessed with the ENLIST ENL Severity Scale. The Cronbach alpha of the scale and each item was calculated to determine the internal consistency of the scale. The ENLIST ENL Severity Scale had good internal consistency and this improved following removal of six items to give a Cronbach's alpha of 0.77. The cut off between mild ENL and more severe disease was 9 determined using ROC curves. The minimal important difference of the scale was determined to be 5 using both participant and physician ratings of change. CONCLUSIONS: The 10-item ENLIST ENL Severity Scale is the first valid, reliable and responsive measure of ENL severity and improves our ability to assess and compare patients and their treatments in this severe and difficult to manage complication of leprosy. The ENLIST ENL Severity Scale will assist physicians in the monitoring and treatment of patients with ENL. The ENLIST ENL Severity Scale is easy to apply and will be useful as an outcome measure in treatment studies and enable the standardisation of other clinical and laboratory ENL research

Serum Metabolomics Reveals Higher Levels of Polyunsaturated Fatty Acids in Lepromatous Leprosy: Potential Markers for Susceptibility and Pathogenesis

Leprosy is an infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae. M. leprae infects the skin and nerves, leading to disfigurement and nerve damage, with the severity of the disease varying widely. We believe there are multiple factors (genetic, bacterial, nutritional and environmental), which may explain the differences in clinical manifestations of the disease. We studied the metabolites in the serum of infected patients to search for specific molecules that may contribute to variations in the severity of disease seen in leprosy. We found that there were variations in levels of certain lipids in the patients with different bacterial loads. In particular, we found that three polyunsaturated fatty acids (PUFAs) involved in the inhibition of inflammation were more abundant in the serum of patients with higher bacterial loads. However, we do not know whether these PUFAs originated from the host or the bacteria. The variations in the metabolite profile that we observed provide a foundation for future research into the explanations of how leprosy causes disease

Combination chemoprophylaxis and immunoprophylaxis in reducing the incidence of leprosy

Malcolm S Duthie,1 Marivic F Balagon2 1Infectious Disease Research Institute, Seattle, WA, USA; 2Cebu Skin Clinic, Leonard Wood Memorial Center for Leprosy Research, Cebu City, the Philippines Abstract: Leprosy is a complex infectious disease caused by Mycobacterium leprae that is a leading cause of nontraumatic peripheral neuropathy. Current control strategies, with a goal of early diagnosis and treatment in the form of multidrug therapy, have maintained new case reports at ~225,000 per year. Diagnostic capabilities are limited and even with revisions to multidrug therapy regimen, treatment can still require up to a year of daily drug intake. Although alternate chemotherapies or adjunct immune therapies that could provide shorter or simpler treatment regimen appear possible, only a limited number of trials have been conducted. More proactive strategies appear necessary in the drive to elimination. As a prevention strategy, most chemoprophylaxis campaigns to date have provided about a 2-year protective window. Vaccination, in the form of a single bacillus Calmette–Guérin (BCG) immunization, generally provides ~50% reduction in leprosy cases. Adapting control strategies to provide both chemoprophylaxis and immunoprophylaxis has distinct appeal, with chemoprophylaxis theoretically buttressed by vaccination to generate immediate protection that can be sustained in the long term. We also discuss simple assays measuring biomarkers as surrogates for disease development or replacements for invasive, but not particularly sensitive, direct measures of M. leprae infection. Such assays could facilitate the clinical trials required to develop these new chemoprophylaxis, immunoprophylaxis strategies, and transition into wider use. Keywords: mycobacteria, treatment, antibiotics, T-cell, vaccine, prevention Hansen's diseas

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

Strategic profiling for behaviour visualization of malicious node in MANETs using game theory

In Mobile Adhoc Network (MANET), one of the precarious problems is of identifying the malicious nodes. The identification and later mitigation of the same becomes an immensely difficult task especially when selfish / erroneous nodes exist along with normal collaborative nodes in the Regular camp. The presence of selfish nodes is potentially harmful as similar behaviour can be imitated by malicious nodes which are the point of concern of many security aspects. The paper accentuates the use of game theory and probability theory considering selfish nodes in the regular node camp while modelling the Regular versus Malicious node game and thereby enhancing the prior mathematical schema of strategical decision making to accommodate for the same. The framework effectively represent the various unpredictable actions of node cooperation, node declination, node attacks, as well as node reporting that can model the strategic profiling of various mobile nodes. A significant focus is given on Perfect Bayesian Equilibrium (PBE) strategy which forms as the basis of all the result analysis. The enhancement is shown in terms of 63% lesser false positives which favors higher overall network utility (modelled as utility of regular nodes in the game) with selfish / erroneous nodes existing in the network when collating the proposed schema with prior work

Diversity and composition of riparian vegetation across forest and agro-ecosystem landscapes of Cabadbaran River, Agusan del Norte, Philippines

The Cabadbaran River Irrigation System (CabRIS) supports about 3,212 hectares of farmland for irrigation. Unfortunately, the local irrigation office reported an insufficient water supply for irrigation to serve the entire service area in the past cropping seasons. The water yield has been dwindling; hence, an irrigation system management plan will address the water resource crisis. As a component of the project "Cabadbaran River Irrigation System Management Plan for Irrigation Water Resources (2022-2026)", the biophysical team carried out a floristic assessment for the entire watershed. The study used the quadrat-transect sampling method to assess and characterise the structure and species composition of the riparian areas of the main Cabadbaran River, Cabadbaran City, Agusan del Norte, Philippines. Results recorded about 109 morpho-species belonging to 46 families and 88 genera from the sampling sites. Nineteen species were listed either on the Philippine Red List or the IUCN Red List of Threatened Species. The plant diversity assessment revealed that biodiversity in riparian forests in the watershed was low to very low due to the massive rampant disturbance in the area. The riparian ecosystem of the Cabadbaran River represents a fragile ecosystem that is threatened by increasing demands on the regional water supply and the conversion of lands into tree plantations and agriculture. Addressing these driving forces causing biodiversity loss will impart a significant challenge for irrigation and land managers in the region

Diversity and composition of riparian vegetation across forest and agro-ecosystem landscapes of Cabadbaran River, Agusan del Norte, Philippines

The Cabadbaran River Irrigation System (CabRIS) supports about 3,212 hectares of farmland for irrigation. Unfortunately, the local irrigation office reported that only a small percentage of its entire service area was irrigated during the past cropping seasons. The water yield has been dwindling; hence an irrigation system management plan will address the water resource crisis. As a project component, the team carried out a floristic assessment for the entire watershed. The study used the quadrat-transect sampling method to assess and characterize the structure and species composition of the riparian areas of the main Cabadbaran River, Cabadbaran City, Agusan del Norte, Philippines. Results recorded about 109 morpho-species belonging to 46 families and 88 genera from the sampling sites. Nineteen species were listed either on the Philippine Red List and or on the IUCN Red List of Threatened Species. The result of the plant diversity assessment revealed that biodiversity in riparian forests in the watershed was low to very low due to the massive rampant disturbance in the area. The riparian ecosystem of the Cabadbaran River represents a fragile ecosystem that is threatened by increasing demands on the regional water supply and the conversion of lands into tree plantations and agriculture. Addressing these driving forces causing biodiversity loss will impart a significant challenge for irrigation and land managers in the region