Prevalence of disability among leprosy patients and effectiveness of standard predonisolone treatment for leprosy reaction at field level in some place of Myanmar are shown in this paper as results of joint leprosy research collaboration. WHO disability grading was measured for all newly registered leprosy patients through 2007 in 5 selected townships of Ayeyarwaddy Division, with the results of G0 = 66.3%, GI = 18.9%, GII = 14.7%(N = 95). The cross-sectional disability survey at selected 9 townships in Mandalay, Sagaing and Magway Division for all registered patients who had completed WHO/MDT done by JICA project in 2003/4 showed G0 = 62.5%, GI = 2.4%, GII = 35.1%(N = 10,528). From these two data, it is supposed that considerable number of patients with G1 at registered time developed worsening of disability from G1 to G2. Proportion of G0 also reduced a little bit in patients who completed WHO/MDT. Early detection and proper treatment of leprosy reaction are one of the main issues of prevention of disability. Effectiveness of leprosy reaction services were evaluated at Mandalay Special Skin Clinic, where WHO fixed regimen of prednisolone were given as routine service. 100 cases were evaluated who developed leprosy reactions from 1st December 2007 to 31st December 2008 and identified severe reaction who needed oral prednisolone treatment. Evaluation criteria of "effective" was defined as "no more signs and symptoms of reactions were present after treatment. And "less effective" was defined as "more than one of signs and symptoms were still remained after treatment". Over all "effective" was 36 (36%) and "less effective" was 64 (64%). It was also found that rates of improvement of nerve functions, either in sensory or in motor, were little after the standard treatment.

BCG (bacille Calmette-Guérin) vaccines are at once among the least satisfactory and yet the most widely used of all vaccines today. Their variable efficacy against tuberculosis and leprosy is still not understood and points to a fundamental unsolved problem in vaccine immunology. The extensive use of BCG vaccines means that there are few BCG-free populations in the world that would be suitable for trials of future antimycobacterial vaccines. These facts have implications with regard to strategies for the development and testing of new vaccines against mycobacterial diseases.

There is a longstanding debate over the implications of natural and vaccine-induced delayed type hypertensivity for protective immunity to mycobacterial infections. The identification of correlates of vaccine-induced protective immunity should help explain the inconsistent behaviour of BCG vaccines in different populations and assist in efforts to devise improved vaccines. More than 70,000 subjects in Karonga District, northern Malawi were skin tested with soluble antigens of the tubercle and leprosy bacilli, and then followed up for five years for tuberculosis and leprosy incidence. Incidence rate ratios were calculated to compare subjects with different levels of prior skin test sensitivity, after controlling for the effects of age, sex and previous BCG vaccination. BCG vaccination protected against leprosy without persistent delayed-type hypersensitivity to tuberculin or to soluble antigens of the leprosy bacillus. In subjects who had not received BCG, hypersensitivity to tuberculin or to antigens of the leprosy bacillus was associated with strong protection against leprosy. In BCG-vaccinated and unvaccinated subjects, there was a J-shaped relation between hypersensitivity to tuberculin and subsequent rates of tuberculosis, with lowest rates associated with low grade sensitivity (induration 1-10 mm). This study shows that delayed-type hypersensitivity to mycobacterial antigens has different implications for tuberculosis and leprosy: low-level hypersensitivity (probably attributable to environmental mycobacteria) is associated with protection, but persistent vaccine-associated hypersensitivity to mycobacterial antigens is not a correlate of vaccine-derived protection against mycobacterial diseases.

The scope of the tuberculosis (TB) epidemic in the world today is enormous, with about 30 million active cases. Current research into preventing the spread of TB is focused on development of new drugs to inactivate Mycobacterium tuberculosis, the causative agent of TB, as well as on identifying the critical steps of host defense to infection with Mycobacteria, which might also yield therapeutic targets. Our infection genomics approach toward the latter strategy has been to isolate and characterize a mouse gene, Bcg (Nramp1), which controls natural susceptibility to infection with Mycobacteria, as well as Salmonella and Leishmania. Through comparative genomics, we have identified the homologous human NRAMP1 gene, alleles of which are now being used for tests of linkage with TB and leprosy.

The pathogens responsible for leprosy, tuberculosis and the leishmaniases can induce different classes of immunity, but protection is provided only by a cell-mediated response. Here, Peter Bretscher proposes a strategy to achieve an immunological imprint that ensures a stable cell-mediated response upon natural infection.

Notwithstanding the elimination efforts, leprosy control programs face the problem of many leprosy patients remaining undetected. Leprosy control focuses on early diagnosis through screening of household contacts, although this high-risk group generates only a small proportion of all incident cases. For the remaining incident cases, leprosy control programs have to rely on self-reporting of patients. We explored the extent to which other contact groups contribute to incident leprosy. We examined retrospectively incident leprosy over 25 years in a high-endemic village of 2283 inhabitants in Sulawesi, Indonesia, by systematically reviewing data obtained from the local program and actively gathering data through interviews and a house-to-house survey. We investigated the contact status in the past of every incident case. In addition to household contact, we distinguished neighbor and social contacts. Of the 101 incident cases over a 25-year period, 79 (78%) could be associated to contact with another leprosy patient. Twenty-eight (28%) of these 101 cases were identified as household contacts, 36 (36%) as neighbors, and the remaining 15 (15%) as social contacts. Three patients had not had a traceable previous contact with another leprosy patient, and no information could be gathered from 19 patients. The median span of time from the registration of the primary case to that of the secondary case was 3 years; 95% of the secondary cases were detected within 6 years after the primary case. The estimated risk for leprosy was about nine times higher in households of patients and four times higher in direct neighboring houses of patients compared to households that had had no such contact with patients. The highest risk of leprosy was associated with households of multibacillary patients. The risk of leprosy for households of paucibacillary patients was similar to the risk of leprosy for direct neighboring houses of multibacillary patients, indicating that both the type of leprosy of the primary case and the distance to the primary case are important contributing factors for the risk of leprosy. Contact with a leprosy patient is the major determinant in incident leprosy; the type of contact is not limited to household relationships but also includes neighbor and social relationships. This finding can be translated into a valuable and sustainable tool for leprosy control programs and elimination campaigns by focusing case detection and health promotion activities not only on household contacts but also on at least the neighbors of leprosy cases.

In an attempt to find a vaccine that gives greater and more consistent protection against leprosy than BCG vaccine, we compared BCG with and without killed Mycobacterium leprae in Venezuela. Close contacts of prevalent leprosy cases were selected as the trial population since they are at greatest risk of leprosy. Since 1983, 29,113 contacts have been randomly allocated vaccination with BCG alone or BCG plus 6 x 10(8) irradiated, autoclaved M leprae purified from the tissues of infected armadillos. We excluded contacts with signs of leprosy at screening and a proportion of those whose skin-test responses to M leprae soluble antigen (MLSA) were 10 mm or more (positive reactions). By July, 1991, 59 postvaccination cases of leprosy had been confirmed in 150,026 person-years of follow-up through annual clinical examinations of the trial population (31 BCG, 28 BCG/M leprae). In the subgroup for which we thought an effect of vaccination was most likely (onset more than a year after vaccination, negative MLSA skin-test response before vaccination), leprosy developed in 11 BCG recipients and 9 BCG/M leprae recipients; there were 18% fewer cases (upper 95% confidence limit [CL] 70%) in the BCG/M leprae than in the BCG alone group. For all cases with onset more than a year after vaccination irrespective of MLSA reaction the relative efficacy was 0%(upper 95% CL 54%; 15 cases in each vaccine group). Retrospective analysis of data on the number of BCG scars found on each contact screened suggested that BCG alone confers substantial protection against leprosy (vaccine efficacy 56%, 95% CL 27-74%) and there was a suggestion that several doses of BCG offered additional protection. There is no evidence in the first 5 years of follow-up of this trial that BCG plus M leprae offers substantially better protection against leprosy than does BCG alone, but the confidence interval on the relative efficacy estimate is wide.

Can leprosy be eliminated? This paper considers the question against the background of the WHO programme to eliminate leprosy. In 1991 the World Health Assembly set a target of eliminating leprosy as a public health problem by 2000. Elimination was defined as reaching a prevalence of < 1 case per 10 000 people. The elimination programme has been successful in delivering highly effective antibiotic therapy worldwide. However, despite this advance, new-case detection rates remain stable in countries with the highest rates of endemic leprosy, such as Brazil and India. This suggests that infection has not been adequately controlled by antibiotics alone. Leprosy is perhaps more appropriately classed as a chronic stable disease than as an acute infectious disease responsive to elimination strategies. In many countries activities to control and treat leprosy are being integrated into the general health-care system. This reduces the stigma associated with leprosy. However, leprosy causes long-term immunological complications, disability and deformity. The health-care activities of treating and preventing disabilities need to be provided in an integrated setting. Detecting new cases and monitoring disability caused by leprosy will be a challenge. One solution is to implement long-term surveillance in selected countries with the highest rates of endemic disease so that an accurate estimate of the burden of leprosy can be determined. It is also critical that broad-based research into this challenging disease continues until the problems are truly solved.

More than 36000 individuals living in rural Malawi were skin tested with antigens derived from 12 different species of environmental mycobacteria. Most were simultaneously tested with RT23 tuberculin, and all were followed up for both tuberculosis and leprosy incidence. Skin test results indicated widespread sensitivity to the environmental antigens, in particular to Mycobacterium scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with evidence of exposure to 'fast growers'(i.e. with induration to antigens from fast growers which exceeded their sensitivity to tuberculin), but not those exposed to 'slow growers', were at reduced risk of contracting both tuberculosis and leprosy, compared to individuals whose indurations to the environmental antigen were less than that to tuberculin. This evidence for cross protection from natural exposure to certain environmental mycobacteria may explain geographic distributions of mycobacterial disease and has important implications for the mechanisms and measurement of protection by mycobacterial vaccines.