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Leprosy remains a health problem in several countries. Current management of patients with leprosy is complex and requires multidrug therapy. Nonetheless, antibiotic treatment is insufficient to prevent nerve disabilities and control Mycobacterium leprae. Successful infectious disease treatment demands an understanding of the host immune response against a pathogen. Immune-based therapy is an effective treatment option for malignancies and infectious diseases. A promising therapeutic approach to improve the clinical outcome of malignancies is the blockade of immune checkpoints. Immune checkpoints refer to a wide range of inhibitory or regulatory pathways that are critical for maintaining self-tolerance and modulating the immune response. Programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4, and lymphocyte-activation gene-3 are the most important immune check- point molecules. Several pathogens, including M. leprae, are supposed to utilize these mechanisms to evade the host immune response. Regulatory T cells and expression of co-inhibitory molecules on lymphocytes induce specific T-cell anergy/exhaustion, leading to disseminated and progressive disease. From this perspective, we outline how the co-inhibitory molecules PD-1, PD-L1, and Th1/Th17 versus Th2/Treg cells are balanced, how antigen-presenting cell maturation acts at different levels to inhibit T cells and modulate the development of leprosy, and how new interventions interfere with leprosy development. [ABSTRACT FROM AUTHOR]

Background: While prednisolone is commonly used to treat recent nerve function impairment (NFI) in leprosy patients, the optimal treatment duration has not yet been established. In this “Treatment of Early Neuropathy in Leprosy” (TENLEP) trial, we evaluated whether a 32-week prednisolone course is more effective than a 20-week course in restoring and improving nerve function. Methods: In this multi-centre, triple-blind, randomized controlled trial, leprosy patients who had recently developed clinical NFI (<6 months) were allocated to a prednisolone treatment regimen of either 20 weeks or 32 weeks. Prednisolone was started at either 45 or 60 mg/day, depending on the patient’s body weight, and was then tapered. Throughout follow up, NFI was assessed by voluntary muscle testing and monofilament testing. The primary outcome was the proportion of patients with improved or restored nerve function at week 78. As secondary outcomes, we analysed improvements between baseline and week 78 on the Reaction Severity Scale, the SALSA Scale and the Participation Scale. Serious Adverse Events and the need for additional prednisolone treatment were monitored and reported. Results: We included 868 patients in the study, 429 in the 20-week arm and 439 in the 32-week arm. At 78 weeks, the proportion of patients with improved or restored nerve function did not differ significantly between the groups: 78.1% in the 20-week arm and 77.5% in the 32-week arm (p = 0.821). Nor were there any differences in secondary outcomes, except for a significant higher proportion of Serious Adverse Events in the longer treatment arm. Conclusion: In our study, a 20-week course of prednisolone was as effective as a 32-week course in improving and restoring recent clinical NFI in leprosy patients. Twenty weeks is therefore the preferred initial treatment duration for leprosy neuropathy, after which likely only a minority of patients require further individualized treatment. [ABSTRACT FROM AUTHOR]

Background: Leprosy has a wide range of clinical and socio-economic consequences. India, Indonesia and Nepal contribute significantly to the global leprosy burden. After integration, the health systems are pivotal in leprosy service delivery. The Leprosy Post Exposure Prophylaxis (LPEP) program is ongoing to investigate the feasibility of providing single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) to the contacts of leprosy cases in various health systems. We aim to compare national leprosy control programs, and adapted LPEP strategies in India, Nepal and Indonesia. The purpose is to establish a baseline of the health system's situation and document the subsequent adjustment of LPEP, which will provide the context for interpreting the LPEP results in future.Methods: The study followed the multiple-case study design with single units of analysis. The data collection methods were direct observation, in-depth interviews and desk review. The study was divided into two phases, i.e. review of national leprosy programs and description of the LPEP program. The comparative analysis was performed using the WHO health system frameworks (2007).Results: In all countries leprosy services including contact tracing is integrated into the health systems. The LPEP program is fully integrated into the established national leprosy programs, with SDR and increased documentation, which need major additions to standard procedures. PEP administration was widely perceived as well manageable, but the additional LPEP data collection was reported to increase workload in the first year.Conclusions: The findings of our study led to the recommendation that field-based leprosy research programs should keep health systems in focus. The national leprosy programs are diverse in terms of organizational hierarchy, human resource quantity and capacity. We conclude that PEP can be integrated into different health systems without major structural and personal changes, but provisions are necessary for the additional monitoring requirements. [ABSTRACT FROM AUTHOR]

This paper considers the changing medical environment in the way leprosy was experienced from around the turn of the 20th century until the early 21st century. The differing understandings of the disease and corresponding treatments not only affected patients directly, but influenced attitudes towards the disease which in turn impacted upon leprosy sufferers. Forty interviews were conducted between 2004 and 2008 with people who had suffered leprosy in Fiji, New Caledonia, Tonga, Vanuatu and Samoa. These sources are used to describe the changing experiences of those living with leprosy and its consequences in the second half of the period under survey. [ABSTRACT FROM PUBLISHER]

Nitazoxanide (NTZ) is an anti-parasitic drug that also has activity against bacteria, including Mycobacterium tuberculosis. Our data using both radiorespirometry and live-dead staining in vitro demonstrate that NTZ similarly has bactericidal against M. leprae. Further, gavage of M. leprae-infected mice with NTZ at 25mg/kg provided anti-mycobacterial activity equivalent to rifampicin (RIF) at 10 mg/kg. This suggests that NTZ could be considered for leprosy treatment. [ABSTRACT FROM AUTHOR]

Previous studies suggest that coinfection of leprosy and human immunodeficiency virus (HIV) does not decrease the frequency and intensity of leprosy reactions. However, the immunological aspects of leprosy reactions in coinfected patients remain obscure, with a limited number of studies showing contradictory results. Observational study using tissue samples collected during leprosy reactions from 15 patients coinfected with leprosy and HIV and from 15 patients with leprosy alone. Patients were part of a prior larger cohort study of leprosy patients with and without HIV coinfection. Specific antibodies were used to detect IL-1β and IL-6 expression in skin biopsy tissue cells. IL-1β and IL-6 expression was similar between leprosy patients with and without HIV coinfection (p > 0.05). Coinfected and non-coinfected tissues showed similar levels of IL-1β and IL-6 expression for type 1 reactions. A trend towards increased levels of IL-1β and IL-6 expression was observed in tissue from coinfected patients (p = 0.0024). The expression of IL-1β and IL-6 during leprosy reactions did not differ significantly between tissues obtained from leprosy patients with and without HIV coinfection. Therefore, we conclude that HIV coinfection does not affect the immunological pattern of leprosy reactions. [ABSTRACT FROM AUTHOR]

When Hansen’s disease became treatable in Taiwan in the mid-20th century, a group of Hansen’s disease patients lost their sick role despite still having lingering symptoms that continued to evolve. While sociologists have explored in-depth situations in which the social role of the sick is ambiguous, few studies have investigated body experiences under liminality that requires sick people to find a new sick role. Living with lingering symptoms in a post–Hansen’s disease world, the Hansen’s disease patients I have studied face the conundrum of having to find an alternative sick role. Ethnographic fieldwork demonstrates how patients develop a specific set of body techniques that shape and are shaped by their membership in a patient community. Exploring the reinforcing projects of re-embodiment and sociality around Hansen’s disease, I argue that patients are able both to legitimate each other’s feelings of sickness and to use those feelings to manage their illness and, as such, to collectively acquire an alternative sick role. Adding to existing discussions of active patients, this article identifies the body mechanical as a way of practicing active patienthood organized around fixing, trials, mending and functionality. [ABSTRACT FROM AUTHOR]

Background: This study assessed trends of tuberculosis (TB) case notification rate (CNR) and treatment outcomes between 2011 and 2015 in Lagos State, Nigeria. Methods: A retrospective review of TB notification data to the Lagos State Tuberculosis and Leprosy Control Programme (LSTBLCP) between 1 January 2011 and 31 December 2015 was conducted. Results: A total of 44 516 TB cases were notified during the study period, representing 9.4% of the national figure. The male:female ratio was 1.3:1. About 53%, 44.1% and 2.7% of patients were smear positive, smear negative and extrapulmonary TB cases, respectively. TB notification increased by 12.2% between 2011 and 2013 and subsequently declined by 7.2% in 2015 relative to 2013. The TB CNR declined from 82.9 per 100 000 in 2013 to 72.1 per 100 000 in 2015. However, directly observed treatment short course (DOTS) and microscopy site expansion increased from 0.3 to 0.64 per 25 000 population and from 0.16 to 0.4 per 50 000 population, respectively, from 2011 to 2015. Similarly, there was a slight increase in treatment success rate, from 80.1% in 2011 to 82% in 2015. Conclusion: The CNR declined in Lagos State despite an increasing trend in DOTS and microscopy site expansions between 2013 and 2015. The LSTBLCPs need to re-engineer current strategies of active TB case findings in order to improve case notification in the state. [ABSTRACT FROM AUTHOR]

Background: Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using next generation sequencing and bioinformatics analysis of Mycobacterium leprae DNA present in human skin. Methodology: DNA was isolated by means of optimized extraction and enrichment methods from samples from three recurrent cases in leprosy patients participating in an open-label, randomized, controlled clinical trial of uniform MDT in Brazil (U-MDT/CT-BR). Genome-wide sequencing of M. leprae was performed and the resultant sequence assemblies analyzed in silico. Principal findings: In all three cases, no mutations responsible for resistance to rifampicin, dapsone and ofloxacin were found, thus eliminating drug resistance as a possible cause of disease recurrence. However, sequence differences were detected between the strains from the first and second disease episodes in all three patients. In one case, clear evidence was obtained for reinfection with an unrelated strain whereas in the other two cases, relapse appeared more probable. Conclusions/Significance: This is the first report of using M. leprae whole genome sequencing to reveal that treated and cured leprosy patients who remain in endemic areas can be reinfected by another strain. Next generation sequencing can be applied reliably to M. leprae DNA extracted from biopsies to discriminate between cases of relapse and reinfection, thereby providing a powerful tool for evaluating different outcomes of therapeutic regimens and for following disease transmission. [ABSTRACT FROM AUTHOR]

Background: Infectious agents can activate self-reactive T cells. In general, infections trigger various mechanisms, including a lack of auto-tolerance, induction of costimulatory molecules on antigen presenting cells, and molecular simulation, in addition to cross-reactions between microbial antigens and self-antigens. HIV and leprosy coinfections lead to self-immunity with the production of autoantibodies. However, not enough data on the immune behaviour associated with this coinfection are available. Therefore, this study focused on the detection of autoantibodies against cellular antigens (AACA) in individuals with HIV and leprosy coinfection in the Amazon region. Methods: Patients were distributed into four groups according to their infections: (i) coinfection with HIV and leprosy (n = 23), (ii) infection with leprosy (n = 33), (iii) infection with HIV/AIDS (n = 25), and (iv) healthy blood donor controls (n = 100). AACA were identified by indirect immunofluorescence and the samples were tested using a commercial diagnosis kit containing the antinuclear antibody HEp-2. Results: Morphologically, all stages of cell division were assessed in addition to the morphological features associated with the nuclear matrix, nucleolus, mitotic spindle, and cytoplasm. There was a high prevalence of AACA in the coinfection group (47.8%, n = 11) when compared with the control group of healthy blood donors (2.0%). The results showed predominantly cytoplasmic staining in all groups analysed, and no difference was observed between the presence or absence of AACA and the leprosy forms (paucibacillary and multibacillary) in the coinfection group. Conclusions: The results of this study show that despite the tendency of coinfected patients to have higher levels of autoantibodies, no correlation was observed between clinical and laboratorial variables and morbidity associated with HIV and leprosy coinfections or the levels of AACA in the serum of coinfected patients. These data are important to elucidate this complex relationship between HIV and leprosy and thus improve the follow-up of these patients. [ABSTRACT FROM AUTHOR]

Mycobacterium leprae (M. leprae) infection causes nerve damage and the condition worsens often during and long after treatment. Clearance of bacterial antigens including lipoarabinomannan (LAM) during and after treatment in leprosy patients is slow. We previously demonstrated that M. leprae LAM damages peripheral nerves by in situ generation of the membrane attack complex (MAC). Investigating the role of complement activation in skin lesions of leprosy patients might provide insight into the dynamics of in situ immune reactivity and the destructive pathology of M. leprae. In this study, we analyzed in skin lesions of leprosy patients, whether M. leprae antigen LAM deposition correlates with the deposition of complement activation products MAC and C3d on nerves and cells in the surrounding tissue. Skin biopsies of paucibacillary (n = 7), multibacillary leprosy patients (n = 7), and patients with erythema nodosum leprosum (ENL) (n = 6) or reversal reaction (RR) (n = 4) and controls (n = 5) were analyzed. The percentage of C3d, MAC and LAM deposition was significantly higher in the skin biopsies of multibacillary compared to paucibacillary patients (p = <0.05, p = <0.001 and p = <0.001 respectively), with a significant association between LAM and C3d or MAC in the skin biopsies of leprosy patients (r = 0.9578, p< 0.0001 and r = 0.8585, p<0.0001 respectively). In skin lesions of multibacillary patients, MAC deposition was found on axons and co-localizing with LAM. In skin lesions of paucibacillary patients, we found C3d positive T-cells in and surrounding granulomas, but hardly any MAC deposition. In addition, MAC immunoreactivity was increased in both ENL and RR skin lesions compared to non-reactional leprosy patients (p = <0.01 and p = <0.01 respectively). The present findings demonstrate that complement is deposited in skin lesions of leprosy patients, suggesting that inflammation driven by complement activation might contribute to nerve damage in the lesions of these patients. This should be regarded as an important factor in M. leprae nerve damage pathology. [ABSTRACT FROM AUTHOR]

The article focuses on adoption of several preventive measures against leprosy that leads to reduction in disease incidence. Topics discussed include provision of Bacillus Calmette-Guerin (BCG) vaccines among infants for controlling the disease; examination of Mycobacterium leprae pathogen responsible for disease transmission while treatment of the disease; and utilization of an antibiotics such as chemoprophylaxis for stimulation of an immune response.

Background: Reversal reaction (RR) is an acute reaction on chronic episode which often contributes to withdrawal of treatment and disability in leprosy patients. Previous study showed that mast cells in reactive tuberculoid lesions biopsy material had lower density than non reactive tuberculoid lesions. Granulomatous lesions in leprosy patients with high mast cells density were more likely to progress into severe reversal reaction. Objective: To examine mast cells level in reversal reaction patients (RR) and non-reactional leprosy patients (non-RR) Methods: Fiftysix leprosy patients consist of 28 with reversal reactions and 28 non-reactional leprosy were assessed for mast cells levels by immunohistochemistry staining. The mast cell numbers in both groups were analyzed using Independent T-test. Results: Mast cells were increased in the reversal group (p<0.05). Conclusion: Mast cells level is associated with reversal reaction of leprosy. [ABSTRACT FROM AUTHOR]

Background Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. Objectives To describe the pattern and prevalence of leprosy reactions in the postelimination stage. Methods A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. Results Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. Conclusion The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services. [ABSTRACT FROM AUTHOR]

Background: Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R. Methodology: Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome. Principal findings: 345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia. Conclusions: Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve damage do not improve. Future studies should test giving azathioprine in the treatment of nerve damage and giving a higher dose for 48 weeks to patients. These findings highlight the difficulty in switching off leprosy inflammation and the need for better treatments for reactions and nerve damage. There is also a research need to identify patients who have recurrences and optimize treatments for them. Patients with recurrences may benefit from combined treatment with steroids and azathioprine. We have also shown that significant numbers of patients treated with steroids develop adverse effects and this needs to be highlighted in leprosy programmes. Research is needed to identify patients who do not respond to steroid treatment and develop alternative treatments for them. Trial Registration: ClinicalTrials.gov This trial was registered with the Indian Council of Medical research clinical Trial register as a clinical trial Number— [ABSTRACT FROM AUTHOR]

Leprosy is a bacterial disease caused by M. leprae. Its clinical spectrum reflects the host’s immune response to the M. leprae and provide an ideal model to investigate the host pathogen interaction and immunological dysregulation. Tregs are high in leprosy patients and responsible for immune suppression of the host by producing IL-10 and TGF-β cytokines. In leprosy, plasticity of Tregs remain unstudied. This is the first study describing the conversion of Tregs into Th1-like and Th17-like cells using in vitro cytokine therapy in leprosy patients. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA), rIL-12 and rIL-23 for 48 h. Expression of FoxP3 in CD4 + CD25 + Tregs, intracellular cytokines IFN-γ, TGF-β, IL-10 and IL-17 in Tregs cells were evaluated by flow cytometry (FACS) after stimulation . rIL-12 treatment increases the levels of pStat4 in Tregs and IFN-γ production. In the presence of rIL-23, pStat3 + and IL-17A + cells increase. rIL-12 and r—IL-23 treatment downregulated the FoxP3 expression, IL-10 and TGF-β production by Tregs and enhances the expression of co-stimulatory molecules (CD80, CD86). In conclusion rIL-12 converts Tregs into IFN-γ producing cells through STAT-4 signaling while rIL-23 converts Tregs into IL-17 producing cells through STAT-3 signaling in leprosy patients. This study may helpful to provide a new avenue to overcome the immunosuprression in leprosy patients using in vitro cytokine. [ABSTRACT FROM AUTHOR]

Nerve function impairment (NFI) in leprosy may occur and progress despite multidrug therapy alone or in combination with corticosteroids. We observed improvement in neuritis when minocycline was administered in patients with type 2 lepra reaction. This prompted us to investigate the role of minocycline in recent onset NFI, especially in corticosteroid unresponsive leprosy patients. Leprosy patients with recent onset clinical NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3 months to these patients. The primary outcome was the proportion of patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI. Secondary outcomes included any improvement in nerve tenderness and pain. In this pilot study, 11 patients were recruited. The progression of NFI was halted in all; with 9 out of 11 patients (81.82%) showing ?restored? or ?improved? sensory or motor nerve functions, on assessment with MFT and VMT. No serious adverse effects due to minocycline were observed. Our pilot study demonstrates the efficacy and safety of minocycline in recent onset NFI in leprosy patients. However, larger and long term comparative trials are needed to validate the efficacy of minocycline in leprosy neuropathy. [ABSTRACT FROM AUTHOR]

Aim: to analyze the meaning of leprosy for 28 women who were diagnosed with this disease and under medical supervision in an infectology service located in Petrolina, Pernambuco, Brazil. Method: the data were collected through individual interviews and its processing happened in virtue of content analysis technique. Results: the verbal reports revealed that the disease caused changes in daily life in familiar, professional and economic aspects. The disease also affected the body image that women had about themselves, which indicated that prejudice is still present in social and familial relations. Multidrug therapy was seen as something positive, but it caused much discomfort and some women did not feel really cured at the end of the treatment. Conclusion: Leprosy affects the lives of women in different aspects and economically disadvantaged people are more vulnerable to the disease. [ABSTRACT FROM AUTHOR]

Introduction: With a sustained effort, India achieved the goal of elimination of leprosy in December, 2005 (PR- 0.95/10,000). Since 2001, MDT services in India were integrated with the general health services, thus posing various operational challenges in programme management. With a view to maximize the effectiveness of health education programme, it needs to assess current status of perception and practices of the family members taking care of the patients of the most stigmatized disease so as to adopt appropriate changes accordingly. Aim(s)/Objective(s): To assess perception & attitude about leprosy among family members in both high & low endemic districts. Materials and Method: 25% of leprosy patients getting MDT in 25% blocks of 3 high prevalent & all patients in 25% blocks in 3 low prevalent districts of West Bengal, were initially selected by multi-stage random sampling technique, then family members taking care of the patients, were interviewed. Statistical Analysis: Proportions in respect of different attributes calculated & chi-square used as a test of significance. Results: Total 246 family members of the leprosy patients, 143 from high prevalent & 103 from low prevalent districts were interviewed. 95.5% & 60.1% of family members respectively have heard about leprosy & MDT. Correct knowledge about cause (38.5% vs 32% ), clinical presentation, curability (90% vs 84.5%), infectiousness of the disease(59.4% vs 31%), complication (67.1% vs 52.4%) were found more among family members of high prevalent districts than low prevalent one. 13.59% & 4.2% family members in high & low prevalent districts had belief that leprosy occurred as a result of divine curse. Discrimination towards leprosy patients were found more in low prevalent than high prevalent districts. Conclusions: Knowledge & attitude towards leprosy were found to be better among family members in high prevalent as compared to that of low prevalent districts. [ABSTRACT FROM AUTHOR]

Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients ( n = 113) and control subjects ( n = 117) from the region with the highest incidence for the disease in México. The odds of developing leprosy and lepromatous subtype were 2.12- and 2.74-fold higher in carriers of HLA-A*28, and 2.48- and 4.14-fold higher for leprosy and dimorphic subtype in carriers of DQB1*06. Interestingly, DQB1*07 was overrepresented in healthy individuals, compared to patients with leprosy (OR = 0.08) and the lepromatous subtype (OR = 0.06). These results suggest that HLA-A*28 is a marker for predisposition to leprosy and the lepromatous subtype and DQB1*06 to leprosy and the dimorphic subtype, while DQB1*07 might be a resistance marker in this Mestizo population. [ABSTRACT FROM AUTHOR]

To identify the use of alternative system of medicine other than MDT by leprosy patients. Material and Method : 251 study subjects were selected randomly attending the Skin & VD OPD of S. S. Hospital of IMS, BHU, Varanasi. Questions related to alternative system of medicine were administered to leprosy patients aged 15 years or above by the interviewer himself. Result : MDT was initial treatment of 41.8% of the patients. Homeopathy (36.3%) was the most popular treatment among the alternative system of medicine. About three fourth of patients went for more than one treatment. Conclusion : Homeopaths are hurdle in the success of NLEP. There is need to improve the compliance to MDT. [ABSTRACT FROM AUTHOR]

Background: Detection of Mycobacterium leprae in slit skin smear (SSS) is a gold standard technique for the leprosy diagnosis. Over recent years, molecular diagnosis by using PCR has been increasingly used as an alternative for its diagnosis due to its higher sensitivity. This study was carried out for comparative evaluation of PCR and SSS microscopy in a cohort of new leprosy cases diagnosed in B. P. Koirala Institute of health Sciences, Dharan, Nepal. Methodology/Principal Findings: In this prospective crossectional study, 50 new clinically diagnosed cases of leprosy were included. DNA was extracted from SSS and PCR was carried out to amplify 129 bp sequence of M. leprae repetitive element. Sensitivity of SSS and PCR was 18% and 72% respectively. Improvement of 54% case detection by PCR clearly showed its advantage over SSS. Furthermore, PCR could confirm the leprosy diagnosis in 66% of AFB negative cases indicating its superiority over SSS. In the paucibacillary (PB) patients, whose BI was zero; sensitivity of PCR was 44%, whereas it was 78% in the multibacillary patients. Conclusions/Significance: Our study showed PCR to be more sensitive than SSS microscopy in diagnosing leprosy. Moreover, it explored the characteristic feature of PCR which detected higher level of early stage(PB) cases tested negative by SSS. Being an expensive technique, PCR may not be feasible in all the cases, however, it would be useful in diagnosis of early cases of leprosy as opposed to SSS. [ABSTRACT FROM AUTHOR]

Background: The predictive value of the serology to detection of IgM against the Mycobacterium leprae-derived phenolic glycolipid-I/PGL-I to identify leprosy patients who are at higher risk of developing reactions remains controversial. Whether baseline results of the ML Flow test can predict leprosy reactions was investigated among a cohort of patients enrolled in The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR). Methods: This was a descriptive study focusing on the main clinical manifestations of leprosy patients enrolled in the U-MDT/CT-BR from March 2007 to February 2012 at two Brazilian leprosy reference centers. For research purposes, 753 leprosy patients were categorized according to a modified Ridley-Jopling (R&J) classification and according to the development of leprosy reactions (reversal reaction/RR and erythema nodosum leprosum/ENL), and whether they had a positive or negative bacillary index/BI. Results: More than half of the patients (55.5%) reported leprosy reaction: 18.3% (138/753) had a RR and 5.4% (41/753) had ENL. Leprosy reactions were more frequent in the first year following diagnosis, as seen in 27% (205/753) of patients, while 19% (142/753) developed reactions during subsequent follow-up. Similar frequencies of leprosy reactions and other clinical manifestations were observed in paucibacillary (PB) and multibacillary (MB) leprosy patients treated with U-MDT and regular MDT (R-MDT) (P = 0.43 and P = 0.61, respectively). Compared with PB patients, leprosy reactions were significantly more frequent in MB patients with a high BI, and more patients developed RR than ENL. However, RR and neuritis were also reported in patients with a negative BI. At baseline, the highest rate of ML Flow positivity was observed in patients with a positive BI, especially those who developed ENL, followed by patients who had neuritis and RR. Among reaction-free patients, 81.9% were ML Flow positive, however, the differences were not statistically significant compared to reactional patients (P = 0.45). Conclusions: MB and PB patients treated with R-MDT and U-MDT showed similar frequencies of RR and other clinical manifestations. Positive ML Flow tests were associated with MB leprosy and BI positivity. However, ML Flow test results at baseline showed limited sensitivity and specificity for predicting the development of leprosy reactions. [ABSTRACT FROM AUTHOR]

Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed. [ABSTRACT FROM AUTHOR]

Background & objectives: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. Methods: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. Results: A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. Interpretation & conclusions: We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [ABSTRACT FROM AUTHOR]

Background: Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. Methodology/Principal Findings: To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone–mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. Conclusions/Significance: The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans. [ABSTRACT FROM AUTHOR]

Leprosy is caused by Mycobacterium leprae infection and remains a major public health problem in many areas of the world. Challenges to its timely diagnosis result in delay in treatment, which is usually associated with severe disability. Although phenolic glycolipid (PGL)-I has been reported as auxiliary diagnostic tool, currently there is no serological assay routinely used in leprosy diagnosis. The aim of this study was to evaluate the effectiveness of two related reagents, LID-1 and LID-NDO, for the detection of M. leprae infection. Sera from 98 leprosy patients, 365 household contacts (HHC) and 98 endemic controls from Rio Grande do Norte, Brazil, were evaluated. A subgroup of the HHC living in a hyperendemic area was followed for 7–10 years. Antigen-specific antibody responses were highest in multibacillary (MB) at the lepromatous pole (LL/BL) and lowest in paucibacillary (PB) at the tuberculoid pole (TT/BT). A positive correlation for both anti-LID-1 and anti-LID-NDO antibodies was found with bacterial burden (LID-1, r = 0.84, p<0.001; LID-NDO, r = 0.82, p<0.001), with higher sensitivity than bacilloscopy. According to Receiver Operating Curve, LID-1 and LID-NDO performed similarly. The sensitivity for MB cases was 89% for LID-1 and 95% for LID-NDO; the specificity was 96% for LID-1 and 88% for LID-NDO. Of the 332 HHC that were followed, 12 (3.6%) were diagnosed with leprosy in a median time of 31 (3–79) months after recruitment. A linear generalized model using LID-1 or LID-NDO as a predictor estimated that 8.3% and 10.4% of the HHC would become a leprosy case, respectively. Together, our findings support a role for the LID-1 and LID-NDO antigens in diagnosing MB leprosy and identifying people at greater risk of developing clinical disease. These assays have the potential to improve the diagnostic capacity at local health centers and aid development of strategies for the eventual control and elimination of leprosy from endemic areas. [ABSTRACT FROM AUTHOR]

Statistically speaking, Malawi has achieved the World Health Organisation's target for the elimination of leprosy (<1 case per 10 000 people), yet the disease is still considered a leading cause of long term physical disability. In this case study the authors discuss the presentation of a 39-year-old gentleman to a district hospital in Malawi with multibacillary, lepromatous leprosy. The condition was initially managed in the community as an ‘allergy' which suggests that local barriers currently hinder the detection of leprosy in this developing primary care system. Leprosy is a multi-system disease and this gentleman demonstrated evidence of lepromatous orchitis. Promoting an awareness of these systemic manifestations will increase the the detection of complications and circumvent long term morbidity. Efforts to optimise systems of detection, management and public and professional education are essential to drive eradication in these at-risk populations. At an international level, we must strive to fulfil the objectives outlined by the ‘Enhanced Global Strategy for Further Reducing the Disease Burden due to Leprosy for 2011–2015'. At a national level, local research should delineate community factors that impede the eradication of leprosy. Developing new diagnostic and epidemiologic tools, more efficacious chemoprophylactic regimens and vaccination for endemic regions would facilitate these efforts. [ABSTRACT FROM AUTHOR]

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We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V). After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed. [ABSTRACT FROM AUTHOR]

The benefits of an integrated approach in the future of leprosy control in India are discussed, by involving professionals from different systems of medicine and coordinated by dermatologists working in the field of community dermatology. The low level of education amongst traditional healers has led to misdiagnosis and inappropriate treatment, thus emphasizing the importance of health education for patients, families and local practitioners to enable prompt and appropriate treatment. The Indian systems of medicine though supportive do not have the required rehabilitation services. Traditional health practitioners demonstrated an improved knowledge of leprosy on completion of training, and were able to detect and refer suspect cases with only early signs of disease. [ABSTRACT FROM AUTHOR]

Inadequate education and treatment access make Hansen's disease a global problem. Carville, LA, was an internationally renowned USDHHS Hansen's disease medical/treatment facility that found a cure. The purpose was to verify and summarize 28 archived oral histories of patients/staff from the National Hansen's Disease Museum and record more. The procedure analyzed, classified, chronologized, and summarized unpublished oral histories validated by Garraghan's historical methods. The verified category results were the stigma (contagion; fear; disfigurement) and human rights' discriminations (quarantine law; pseudonyms; no marriage). The is is a unique historical manuscript of patient/staff life at the last U.S. leprosarium for posterity and education. [ABSTRACT FROM AUTHOR]

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Background: Leprosy often heals with residual skin lesions after completion of treatment. WHO recommends fixed duration multidrug therapy (MDT) irrespective of whether lesions clear or persist after treatment. Patients with residual lesions are often unsatisfied and may undergo repeat biopsy and re-treatment. This study was conducted to compare the clinicohistopathological features in paucibacillary leprosy before and after MDT from September 2012 to February 2014. Methods: Sixty-one untreated cases of paucibacillary leprosy were investigated and given standard WHO paucibacillary-MDT for 6 months. Scoring of clinical activity was done; histopathological activity was graded according to granuloma fraction. Forty-four patients who completed the treatment were subjected to posttreatment biopsy. Clinical response to therapy was graded as active, resolving and inactive and histopathological changes were compared in all patients. Results: Among the 44 patients, the lesions were inactive, resolving and active in 39% (17/44), 39% (17/44) and 23% (10/44) of patients, respectively. Histologically, disease was inactive, resolving and active in 30% (13/44), 9% (4/44) and 61% (27/44). But histomorphological features suggesting regression: loose granulomas (59%, 26/44); lymphocyte predominance (66%, 29/44); vacuolar change in epithelioid cell cytoplasm (59%, 26/44), were statistically significant in post-treatment compared to pre-treatment. Conclusions: Although histological resolution is slower than clinical resolution, qualitative histomorphological changes in correlation with clinical inactivity can offer a fair suggestion to the clinician to terminate therapy. [ABSTRACT FROM AUTHOR]

Leprosy, a relatively common chronic contagious disease having diverse modes of clinical presentation, can mimic a variety of unrelated diseases. For proper and adequate treatment, the diagnosis must be made accurately with subtyping which should be done with the help of bacillary index, histopathological features, and clinical correlation. This is extremely important in patient care as paucibacillary and multibacillary types have different modes of treatment. Our aim is to categorize leprosy into various types based on bacillary index, morphological findings both in slit skin smears, and biopsy along with clinical correlation. [ABSTRACT FROM AUTHOR]

Background: Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life. Results: Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36. Conclusions: This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed. [ABSTRACT FROM AUTHOR]

Background: 50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions. Methodology and Principle Findings: Quantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients. Conclusions: Patients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation. [ABSTRACT FROM AUTHOR]

Objective: to summarize the information produced about limitations and disabilities in post-treatment for leprosy. Method: integrative review conducted in May and June 2015 in CINAHL, LILACS, PubMed and Scopus databases, using the indexed descriptors: Leprosy, Patient Discharge and People with Disabilities and their counterparts in English and Spanish, together with the Boolean and operator. Results: we selected 15 studies, of which 26.6% are focused on evaluating the limitation of activities and social participation of the individual in post-treatment for leprosy and another 26.6% for the assessment of physical disabilities. Three categories were identified through thematic analysis: Profile of users in post-treatment for leprosy; Social impact; and post-treatment therapeutic possibilities and followup. Conclusion: studies have shown predominance of multibacillary cases with physical disabilities, limitations in activities and of social participation among users in post-treatment for leprosy, suggesting the need for the continuity of care after release from medication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article discusses a unique case of a miraculous fish therapy used for a variety of skin diseases, which seems to have been practised in the mid-fifth century at the shrine of St. Michael in the city of Germia (mod. Gümüşkonak). It aims to enhance our knowledge of Byzantine therapeutic approaches to ‘elephant disease’ and contribute to debates on modern fish spa therapy. [ABSTRACT FROM PUBLISHER]

The article offers information on levamisole, a synthetic antihelminthic drug that belongs to the class of imidazothiazole derivatives with potent immunomodulatory activity. Topics include the pharmacology, mechanism of action, and its various therapeutic uses in dermatology practice. Information is also provided on its use for treating warts, cutaneous leishmaniasis, and leprosy.

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. [ABSTRACT FROM AUTHOR]

Background: The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). Methods: The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. Principle Findings/Conclusions: Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts. [ABSTRACT FROM AUTHOR]

Chemotherapy of leprosy over the past 70 years has passed through several phases, from sulfones, to clofazimine, and to highly bactericidal drugs like rifampicin. The use particularly of the more potent drugs in effective combinations and the development of standard multidrug therapy regimens have made a huge difference in the successful treatment of leprosy as well as in reducing tremendously the prevalence of leprosy globally. A major contributing factor to development of better drugs and drug combinations has been the introduction of the mouse footpad model to evaluate the in vivo activity of drugs against Mycobacterium leprae . The World Health Organization has recommended multidrug therapy, which has been used to treat more than 15 million patients in the last 30 years and has set an excellent record with regard to its very high rate of cure, very low occurrence of relapse, and very rare occurrence of drug resistance. [ABSTRACT FROM AUTHOR]

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