Leprosy: a glossary.

Leprosy continues to afflict residents from a number of countries in Africa, South America, and southeast Asia, despite the marked reduction in the number of cases of leprosy worldwide, after the introduction of the multidrug regimens as recommended by the World Health Organization (WHO-MDT). With the increasing immigration of individuals from risk areas to Europe and the United States, knowledge of the basic concepts of leprosy would be helpful to clinicians caring for immigrants in nonendemic areas. We present a comprehensive, updated, and critical glossary of the most relevant terms related to leprosy.

[Present leprosy situation in the world in 2011].

The epidemiological situation of leprosy is reported by the health division of each country to WHO. The reported data is collected by WHO and is immediately run on the Weekly Epidemiological Record. On this latest edition, data from the beginning of 2010 was reported. The Enhanced global strategy for further reducing the disease burden due to leprosy (plan period: 2011-2015) emphasizes reducing grade-2 disabilities among new cases. The burden of leprosy continues to decline globally as a result of sustained efforts carried out by national leprosy programmes along with continued support from both national and international partners. Improving the management of complications through the development of an effective referral service and increased community awareness about the disease will ensure that cases present for diagnosis at an early stage and will help reduce the disease burden further.

[Understanding current practice of clinical medicine in the tropics (II). Bacterial and viral diseases. Malnutrition]. / Aspectos básicos en la práctica actual de la medicina clínica en el trópico (II). Enfermedades bacterianas y virales. Malnutrición.

In recent years, a significant number of physicians want to spend part of their medical training in health facilities in developing countries. In this setting, clinical skills are extremely important due to the limited available diagnostic resources. Bacterial diseases are common, but bacterial cultures are rarely accessible. In Africa, tuberculosis affects over 200 cases per 100,000 persons, and more than 22 million people live with HIV infection; both diseases are a serious public health problem. Malnutrition is endemic in many countries in Africa and is compounded by the continuous humanitarian and food crisis. In this paper, basic concepts of epidemiology, clinical features, diagnosis and treatment of major diseases that can be found in a rural health post in the tropics are discussed.

Immunogenicity of Mycobacterium leprae unique antigens in leprosy endemic populations in Asia and Africa.

Ongoing transmission of leprosy is evident from the stable disease incidence in high burden areas. Tools for early detection of Mycobacterium leprae (M. leprae) infection, particularly in sub-clinically infected individuals, are urgently required to reduce transmission. Following the sequencing of the M. leprae genome, many M. leprae-unique candidate proteins have been identified, several of which have been tested for induction of M. leprae specific T cell responses in different leprosy endemic areas. In this study, 21 M. leprae-unique proteins and 10 peptide pools covering the complete sequence of five M. leprae-unique proteins (ML0576, ML1989, ML1990, ML2283, and ML2567) were evaluated in 160 individuals in Nepal and Ethiopia. These included: tuberculoid and borderline tuberculoid (TT/BT), borderline borderline and borderline lepromatous (BB/BL) leprosy patients; healthy household contacts (HHC); tuberculosis (TB) patients and endemic controls (EC). Immunogenicity of the proteins was determined by IFN-gamma secretion via stimulation of PBMC in 6 days lymphocyte stimulation tests (LST) or in whole blood assays (WBA). In LST, BB/BL patients (40%) responded to ML0573 and ML1601 whereas ML1604 was most immunogenic in TT/BT (35%) and HHC (36%). Additionally, significant numbers of EC displayed IFN-gamma production in response to ML0573 (54%), ML1601 (50%) and ML1604 (54%). TB patients on the other hand, hardly responded to any of the proteins except for ML1989. Comparison of IFN-gamma responses to ML0121, ML0141 and ML0188 for TT/BT patients showed specific increase in diluted 6 days WBA compared to the undiluted 24 hours WBA, whereas EC showed a reduced response in the diluted WBA, which may indicate detection of disease-specific responses in the 6 days WBA. In summary, identification of multiple M. leprae proteins inducing M. leprae-specific T cell responses in groups at high risk of developing leprosy may contribute to improve early detection for M. leprae infection.

Buruli ulcer (Mycobacterium ulcerans infection).

Mycobacterium ulcerans is an emerging infection that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). Bone lesions may include reactive osteitis or osteomyelitis beneath skin lesions, or metastatic osteomyelitis from lymphohematogenous spread of M. ulcerans. Pathogenesis is related to a necrotizing and immunosuppressive toxin produced by M. ulcerans, called mycolactone. The incidence of BU is highest in children up to 15 years old, and is a major public health problem in endemic countries due to disabling scarring and destruction of bone. Most patients live in West Africa, but the disease has been confirmed in at least 30 countries. Treatment options for BU are antibiotics and surgery. BCG vaccination provides short-term protection against M. ulcerans infection and prevents osteomyelitis. HIV infection may increase risk for BU, and renders BU highly aggressive. Unlike leprosy and tuberculosis, BU is related to environmental factors and is thus considered non-communicable. The most plausible mode of transmission is by skin trauma at sites contaminated by M. ulcerans. The reemergence of BU around 1980 may be attributable to environmental factors such as deforestation, artificial topographic alterations and increased manual agriculture of wetlands. The first cultivation of M. ulcerans from nature was reported in 2008.

On the origin of leprosy.

Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.

On the origin of leprosy

Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.

Trends in leprosy case detection worldwide since 1985.

Trends in case detection and case detection rate (CDR) since 1985 are described at regional and national levels. Annual case detection by WHO Region was available for 1994-2000. Using different sources, complete time series for case detection were constructed for 1985-1998 for a group of 33 endemic countries cumulatively (top 33), and for 14 individual countries (top 14). Population statistics were used to derive CDRs. India contributed 79% to global case detection in 1998. Africa, the Americas and South-East Asia each contributed about 30% when India is excluded. During 1994-2000, case detection did not decrease in these three WHO Regions. The 33 countries contributed 99% and 98% to global case detection in 1994 and 1998, respectively. Cumulative case detection for the top 33 minus India gradually increased, overall almost doubling. The contribution of the top 14 to case detection of the top 33 hardly changed over time, equalling 96% in 1998 (81% when India is excluded). In terms of annual case detection, Brazil was always ranked second after India; it accounted for 27% of 1998 case detection in the top 33 except India. In 1998, seven of the top 14 countries--including India and Brazil--had CDRs above 2 per 10,000. The CDR did not exceed 1 per 10,000 for the other half. Decreasing tendencies in CDR, either for the whole period or in the 1990s, are observed for four of the top 14 countries (Guinea and three Western Pacific countries: China, Vietnam and the Philippines). In conclusion, there is no general decline in case detection to date, and several important countries still have high CDRs. Prevalence is an irrelevant indicator for monitoring epidemiological changes in leprosy. Trends in the transmission and incidence of leprosy are still completely unclear, necessitating further research. The target to eliminate leprosy as a public health problem, defined as a prevalence of less than 1 per 10,000, is therefore also an inadequate yardstick for decision making on leprosy control.

[Eradication of leprosy and public health. Vaccination and multidrug therapy]. / Perspektywy eliminacji tradu w swiecie. Szczepienia ochronne a leczenie etiotropowe.

Leprosy is a disease, which still affects large populations in the developing countries particularly in Africa, Asia and Latin America. For the last 15 years significant advances have been made towards leprosy elimination. The most effective strategy for leprosy control is an early identification of cases and an effective treatment with multidrug therapy (MDT). The vaccination against leprosy plays only an additional role. There are two possible approaches to develop vaccine against leprosy. One is to produce a vaccine based on organisms related to M. leprae, such as: BCG, ICRC bacillus, Mycobacterium w, Mycobacterium vaccae, Mycobacterium habana. However, these organisms related to M. leprae are not very promising in experimental animal studies. In 1970s a new vaccine was prepared based on killed M. leprae. This vaccine, tested alone and together with BCG revealed little impact on increasing vaccine efficacy. The success in cloning and expressing the M. leprae genome in E. coli created the possibility of moving towards a second generation vaccine using peptide antigens. Up till now only MDT has essential impact on decline of global leprosy prevalence. Out of 122 endemic countries in 1985, 107 countries have reached elimination of leprosy at country level. At the end of 2000 leprosy was a public health problem only in 15 countries (prevalence rate > 1/10.000). Currently leprosy remains a problem mainly in 6 major endemic countries. Among these, India alone accounts for 64% of prevalence and 78% of detection worldwide.

Is soil an alternative source of leprosy infection?

Leprosy is believed to be transmitted only through human contacts. However, many anomalous observations had gradually accumulated which had weakened such beliefs. These are: only 1/3 rd cases of leprosy give a definite history of being transmitted from other known cases; life-long spouses, in whom only one has leprosy, seldom lead to leprosy to others; while MDT applied intensively in most leprosy endemic countries, could successfully reduce incidence of leprosy, however, simultaneously new cases arise unabated. Besides, a close look at animal leprosies also suggested a mode of transmission other than human-type contact. Thus, a search for alternative hypothesis led to the findings that leprosy bacillus (LB) could be a soil chemoautotroph and could facultatively live both in the human body and the soil which could serve as an alternative source of infection. Evaluation of accumulated evidences points to this possibility.

Relapses after fixed duration multiple drug therapy: the AMFES cohort.

Relapse rates after multiple-drug therapy (MDT) have been low, although there remains a concern about the possibility of late relapse in those with an initially high bacterial load. In all, 502 patients in the AMFES cohort completed fixed-duration MDT and are included in this report. There have been no confirmed relapses in the AMFES cohort, in a follow-up period of up to 8 years after completion of treatment, even in the 57 cases with an initial average bacillary index of > or = 4.0, 20 of whom have been followed for more than 5 years after ceasing MDT. Methods of diagnosing a relapse are discussed.