Cost-Effectiveness of Interventions to Prevent Disability in Leprosy: A Systematic Review

Background: Prevention of disability (POD) is one of the key objectives of leprosy programmes. Recently, coverage and access have been identified as the priority issues in POD. Assessing the cost-effectiveness of POD interventions is highly relevant to understanding the barriers and opportunities to achieving universal coverage and access with limited resources. The purpose of this study was to systematically review the quality of existing cost-effectiveness evidence and discuss implications for future research and strategies to prevent disability in leprosy and other disabling conditions. Methodology/Principal Findings: We searched electronic databases (NHS EED, MEDLINE, EMBASE, and LILACS) and databases of ongoing trials (www.controlled-trials.com/mrct/, www.who.int/trialsearch). We checked reference lists and contacted experts for further relevant studies. We included studies that reported both cost and effectiveness outcomes of two or more alternative interventions to prevent disability in leprosy. We assessed the quality of the identified studies using a standard checklist for critical appraisal of economic evaluations of health care programmes. We found 66 citations to potentially relevant studies and three met our criteria. Two were randomised controlled trials (footwear, management of neuritis) and one was a generic model-based study (cost per DALY). Generally, the studies were small in size, reported inadequately all relevant costs, uncertainties in estimates, and issues of concern and were based on limited data sources. No cost-effectiveness data on self-care, which is a key strategy in POD, was found. Conclusion/Significance: Evidence for cost-effectiveness of POD interventions for leprosy is scarce. High quality research is needed to identify POD interventions that offer value for money where resources are very scarce, and to develop strategies aimed at available, affordable and sustainable quality POD services for leprosy. The findings are relevant for other chronically disabling conditions, such as lymphatic filariasis, Buruli ulcer and diabetes in developing countries

Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

Leprosy affects skin and peripheral nerves. Although we have antibiotics to treat the mycobacterial infection, the accompanying inflammation is a major part of the disease process. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called reactions. These are associated with worsening of nerve damage. However, diagnosing these reactions is not straightforward. They can be diagnosed clinically by examination or by microscopic examination of the skin biopsies. We studied a cohort of 303 newly diagnosed leprosy patients in India and compared the diagnosis rates by clinical examination and microscopy and found that the microscopic diagnosis has higher rates of diagnosis for both types of reaction. This suggests that clinicians and pathologists have different thresholds for diagnosing reactions. More work is needed to optimise both clinical and pathological diagnosis. In this cohort 43% of patients had Borderline Tuberculoid leprosy, an immunologically active type, and 20% of the biopsies showed only minimal inflammation, perhaps these patients had very early disease or self-healing. The public health implication of this work is that leprosy centres need to be supported by pathologists to help with the clinical management of difficult cases

Preventing Nerve Function Impairment in Leprosy: Validation and Updating of a Prediction Rule

Leprosy is caused by a bacterium that attacks the peripheral nerves. This may cause nerve function impairment (NFI), resulting in handicaps and disabilities. Therefore, prediction and prevention of NFI is extremely important in the management of leprosy. In 2000, a prediction rule for NFI was published, but circumstances have changed since the study was performed in the 1990s: the leprosy detection delay has shortened and the definition of NFI has changed. The original rule used ‘leprosy classification’ and ‘NFI present at diagnosis’ to predict future NFI. In the current patient population we studied an adjusted rule based on ‘leprosy classification’ and ‘presence of antibodies’. This adjusted rule predicted NFI more often than the original rule. With the adjusted rule it is now also possible to assess NFI risk before the first nerve damage event takes place. This may help doctors and health workers to improve surveillance for people at high risk. Early detection and treatment can then prevent permanent disabilities

Cost-Effectiveness of a Chemoprophylactic Intervention with Single Dose Rifampicin in Contacts of New Leprosy Patients

In 2008, 249,007 new leprosy patients were detected in the world. It therefore remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy. The study is based on a large trial including 21,711 contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to contacts and followed them up for four years. The main outcome measure was the development of clinical leprosy. The cost effectiveness was expressed in US dollars per prevented leprosy case. Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total $6,009 was invested and 38 leprosy cases were prevented after 2 years, costing$158 per prevented leprosy case. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world

Hybridization but No Evidence for Backcrossing and Introgression in a Sympatric Population of Great Reed Warblers and Clamorous Reed Warblers

Hybridization is observed frequently in birds, but often it is not known whether the hybrids are fertile and if backcrossing occurs. The breeding ranges of the great reed warbler (Acrocephalus arundinaceus) and the clamorous reed warbler (A. stentoreus) overlap in southern Kazakhstan and a previous study has documented hybridization in a sympatric population. In the present study, we first present a large set of novel microsatellite loci isolated and characterised in great reed warblers. Secondly, we evaluate whether hybridization in the sympatric breeding population has been followed by backcrossing and introgression

Female sexual preferences toward conspecific and hybrid male mating calls in two species of polygynous deer, Cervus elaphus and C. nippon

The behavioral processes at the basis of hybridization and introgression are understudied in terrestrial mammals. We use a unique model to test the role of sexual signals as a reproductive barrier to introgression by investigating behavioral responses to male sexual calls in estrous females of two naturally allopatric but reproductively compatible deer species, red deer and sika deer. Previous studies demonstrated asymmetries in acoustic species discrimination between these species: most but not all female red deer prefer conspecific over sika deer male calls while female sika deer exhibit no preference differences. Here, we extend this examination of acoustic species discrimination to the role of male sexual calls in introgression between parent species and hybrids. Using two-speaker playback experiments, we compared the preference responses of estrous female red and sika deer to male sexual calls from conspecifics versus red × sika hybrids. These playbacks simulate early secondary contact between previously allopatric species after hybridization has occurred. Based on previous conspecific versus heterospecific playbacks, we predicted that most female red deer would prefer conspecific calls while female sika deer would show no difference in their preference behaviors toward conspecific and hybrid calls. However, results show that previous asymmetries did not persist as neither species exhibited more preferences for conspecific over hybrid calls. Thus, vocal behavior is not likely to deter introgression between these species during the early stages of sympatry. On a wider scale, weak discrimination against hybrid sexual signals could substantially contribute to this important evolutionary process in mammals and other taxa