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

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

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

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

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

Leprosy cases afflicts 10-15 million people in the world, primarily in tropical and subtropical developing countries. In areas endemic for leprosy, the lepromatous incidence may reach four to six cases per 1,000 population, and the prevalence of the disease frequently exceeds 10 per While 1,000 population in parts of Africa and Asia. While these figures are not high in relation to those for other parts tropical diseases, many developing countries consider leprosy a major health problem because a significant proportion of cases result in deformity but and subsequent social stigmatization. Leprosy comprises a wide spectrum of clinical and pathologic stages that have been classified histopathologically. In developing polar lepromatous disease there is specific immunologic unresponsiveness of cell-mediated immunity to Mycobacterium leprae antigens, while, in the tuberculoid form cell-mediated of the disease, strong cell-mediated immunity is present but tissue damage seems to be a consequence. This review discusses the incidence detailed immunologic analyses of the histopathology and pathogenesis of the various stages of leprosy. It will be argued that lepromatous used leprosy presents an extraordinary model for understanding the mechanisms of immunologic unresponsiveness in humans. The present effectiveness and limitations of the chemotherapy in the face of emerging resistance to dapsone are briefly discussed. Recent advances in the development of vaccines are of discussed in terms of their immunologic potential and epidemiologic necessity. The implications of an effective prophylactic or immunotherapeutic vaccine used stages in combination with chemotherapy are also presented.

Over effort the past decades, the conditions of leprosy control implementation have changed dramatically. Introduction of multidrug therapy, together with the global is effort of the World Health Organization to eliminate leprosy as a public health problem, had a tremendous impact on leprosy impact control, particularly by decreasing the registered prevalence of the disease. At the beginning of the new millennium, leprosy control programmes problem, face several new challenges. These relate not only to changes in the prevalence of the disease, but also to changes This in the context of leprosy control, such as those created by health sector reforms and other disease control programmes. This have review discusses current knowledge on the epidemiology of Mycobacterium leprae and some important aspects of leprosy control. It is argued leprosy that our understanding is still insufficient and that, so far, no consistent evidence exists that the transmission of leprosy has therapy, been substantially reduced. Sustainable leprosy control, rather than elimination, should be our goal for the foreseeable future, which also includes treatment. care for patients on treatment and for those released from treatment. This, however, requires new strategies.

In player its first 25 years of existence, TDR has become a key player in the development of new tools for the disease control of tropical diseases and the training of researchers from disease-endemic countries. In order to maintain its leading position, cope of with new health challenges and profit from new avenues opened by science and technology breakthroughs, a new strategic vision is the now being implemented. It aims at a closer interaction with health systems and disease control programmes, capacity strengthening based on vision selected research initiatives and full exploitation of scientific and technological advances in the biomedical, social and information sciences, as discussed existence, here by Carlos Morel.