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Serum beta-glucuronidase in subtypes of leprosy.

Serum beta-glucuronidase activity was estimated using phenolphthalein mono-beta-glucuronic acid as substrate in 176 individuals including 72 lepromatous leprosy patients, 24 patients of borderline leprosy, 42 of borderline tuberculoid and 38 healthy controls. Of these, 35 patients (20 with lepromatous leprosy, 5 with borderline leprosy and 10 with borderline tuberculoid) were untreated. The enzyme levels were increased significantly in all types of leprosy, the highest levels being seen in treated lepromatous leprosy patients (105.0 SU). There was also a significant difference in the enzyme activity between untreated patients and those on combined dapsone and rifampicin therapy, in all three types of leprosy. Among untreated patients, the maximum value observed in lepromatous leprosy was 93.4 SU. The lowest enzyme level in healthy control was 19.5 SU and the maximum was 54.0 SU. The results suggest that in leprosy patients, especially in those on daily multidrug regimens, there is an extensive damage of leucocytes and liver cells where the enzyme is largely present.

Female↗

Immunological response to homologous and heterologous phenolic glycolipid antigens in tuberculosis and leprosy.

The occurrence of IgM antibodies immunoreacting in an ELISA test with five phenolic-glycolipids (GPL) antigens (PGL-Tb 1, from M. tuberculosis; PGL-I, from M. leprae; PGK-K-I, from M. kansasii; Mycoside G, from M. marinum; and Mycoside B, from M. bovis), was examined in the sera of 46 tuberculous patients, 48 multibacillary leprosy patients, 40 paucibacillary leprosy patients and in 134 healthy controls. The sensitivity (97.9) and the specificity (91.8) observed in tuberculous patients with the homologous antigen PGL-Tb 1 underlined the interest of this antigen for case finding in tuberculosis epidemiology. The sensitivity and the specificity observed in multibacillary leprosy patients, respectively 91.7 and 91.8, and in paucibacillary leprosy patients, respectively, 35.0 and 91.7, confirmed the limited value of homologous antigen PGL-I for the serological case finding of leprosy patients in endemic areas with a strong incidence of paucibacillary leprosy forms. The data obtained with the heterologous PGL antigens in tuberculosis and multibacillary leprosy serology were higher than those observed in healthy controls and in paucibacillary leprosy patients. However the ELISA using the heterologous antigens was not useful in diagnosis of active tuberculosis or multibacillary leprosy forms. Healthy controls showed low immunoreactivity against PGL antigens, with the exception of mycoside B.

Adolescent↗

Evaluation of leprosy epidemiology in 12 countries of the Americas, 1980-1983.

To assess the leprosy situation prevailing in 12 countries of Latin America and the Caribbean in 1980-1983, the authors reviewed data on eight indicators--four relating specifically to leprosy cases and four to general health conditions. On the basis of scores derived from these indicators, the 12 countries were classified into three groups wherein the leprosy endemic appeared to be declining, stationary, or increasing. Countries of the first group, where the leprosy endemic appeared to be receding, exhibited generally favorable leprosy-specific indicators and general health indicators, and the findings generally agreed with those of prior leprosy prevalence surveys. Similarly, those in the third group, where the endemic seemed to be increasing, showed generally unfavorable leprosy-specific indicators and general health indicators plus general agreement with prior leprosy prevalence surveys. In contrast, the results obtained for the three countries where the leprosy endemic seemed "stationary" differed substantially from one country to the next--but in all cases the "stationary" situation appeared to depend less upon a stable equilibrium than upon interaction of opposing trends.

Adult↗

Identification of cat leprosy bacillus grown in mice.

Cat leprosy bacilli passaged in mice could be isolated on 1% Ogawa yolk medium. The isolated cat leprosy bacilli which were cultivated successively four times on 1% Ogawa yolk medium produced a leproma in mice. All characteristics of the isolated cat leprosy bacillus were the same as isolated murine leprosy bacillus, as follows: slow grower, light yellowish-white rough colony, production of much coproporphyrin on the medium, heat-resistant catalase negative, heat-resistant phosphatase negative, arylsulfatase negative, niacin negative, hydrolysis of Tween 80 negative, urease negative, nicotinamidase positive, pyrazinamidase positive, cytochrome b1 at 560 nm positive, cytochrome a2 at 630 nm positive, and cytochrome c at 550 nm negative. Cats are susceptible to both cat and murine leprosy bacilli; the bacilli produced a leproma in a newborn cat at 3 to 4 months and in an adult cat at 2 months after inoculation. Many globi of acid-fast bacilli (AFB) were observed in the histopathological sections and the smear preparations of the newborn cat's lepromas, especially in the necrotic areas of the lepromas. Many AFB and polymorphonuclear leukocytes were seen in the histopathological sections and the smear preparations of the adult cat's lepromas. These lepromas formed ulcers by autolysis and healed or absorbed without ulcer formation over the course of months. Large lepromas remained for a long time without ulcer formation and caseation in some cats. Secondary infections with cat and murine leprosy bacilli were done respectively to the right and left femoral subcutaneous regions of newborn cats carrying primary lepromas. After one month, granulomas in which many AFB were observed were produced in both infection sites. Cats are susceptible to infection with cat and murine leprosy bacilli; however, the bacilli did not invade progressively to internal organs or other subcutaneous areas. Cat leprosy bacilli which were passaged in the mouse are identical to murine leprosy bacilli.

Animals↗

Comparability among histopathologists in the diagnosis and classification of lesions suspected of leprosy in Malawi.

Identical slides from 200 biopsies obtained from individuals suspected of having leprosy during the course of an epidemiological survey in Northern Malawi were examined sequentially and independently by three histopathologists, using a standard protocol to report their findings. Their results are compared among themselves and with a standardized clinical assessment of each subject. There was more agreement among the histopathologists as to classification of leprosy cases than there was on the diagnosis of leprosy. The proportion of biopsies considered to show definite evidence of leprosy varied from 39% to 58% among the histopathologists. An appreciable additional proportion of biopsies (11.5% to 38.5% for the three histopathologists) was considered to show evidence suggestive but not pathognomonic of leprosy. Although there was, in general, good agreement on classification, the proportion of biopsies considered to show evidence of indeterminate leprosy varied from 1.5% to 21.5% among the three histopathologists. This suggests that some of the reported differences in the prevalence and proportion of indeterminate leprosy in different populations is due to terminology alone. A follow-up meeting of the study participants revealed that many of the differences in diagnosis certainty were due to difficulties in interpreting evidence of nerve involvement. It is recommended that greater attention be paid to the difficulties of diagnosing leprosy on histopathological as well as clinical grounds. A revised standard protocol for reporting histopathological evidence of leprosy is presented.

Biopsy↗

Hepatitis B surface antigen (HBsAg) in leprosy patients of Calcutta: its prevalence and subtypes.

Hight incidence of hepatitis B surface antigen (HBsAg) in lepromatous leprosy patients have been reported by many workers. This paper reports on a study undertaken over a period of more than two years to determine the prevalence of HBsAg and its major antigenic subtypes amongst the various clinical types of leprosy and apparently healthy individuals of Calcutta population. The overall incidence of HBsAg in lepromatous leprosy is found to be 3.8% (9 out of 234) in our study. The incidence of HBsAg in tuberculoid leprosy and non leprosy control cases were almost identical, 2.5% (11 out of 431) and 2.7% (14 out of 519) respectively. The incidence of HBsAg in lepromatous leprosy in the present study was apparently higher than tuberculoid or non leprosy cases, although statistically not significant. Hence the association between HBsAg and lepromatous leprosy could not be established in our study. None of the major antigenic subtypes of HBsAg could be related to any particular type of leprosy. The subtypes 'ad', 'ay' and 'ar' were present at varying proportions in all the groups tested. The antigenic subtype 'ay' was found to be prevalent in Calcutta population in higher proportions.

Adolescent↗

Community leaders involvement in leprosy health education.

As an alternative approach, 310 community leaders consisting of village political leaders, school teachers, Govt. staff, members of socio-welfare and religious agencies, graduate students and traders from 21 villages of Chingleput district of Tamilnadu (India) were interviewed to explore the possibilities of their involvement in leprosy health education community. Though majority (76%) of respondents were not fully aware about various aspects of leprosy and showed negative reactions (51%) towards leprosy patients; almost all realised the importance of educating community about leprosy for its early control, for which a large majority (88%) of them had expressed their willingness to participate in leprosy health education and control programme by devoting an average of 4.4 +/- 5.4 hours per week. A good number (54%) of them had also been educating people about leprosy in one or the other way. The leaders who had been exposed to leprosy health education especially in recent past, were significantly better equipped with knowledge about leprosy and its control and were much more willing to participate in NLCP, than others. Study concluded that if the community leaders are approached, educate and motivated properly, they would certainly involve themselves to provide a valuable strength to our leprosy health education and control programme.

Health Education↗

Spatial patterns of leprosy in an urban area of central Brazil.

Reported is the spatial variation of leprosy in an urban area of Brazil and its correlation with socioeconomic indicators. From November 1991 to October 1992 a total of 752 newly diagnosed leprosy patients who were attending all outpatient clinics in Goiânia city, central Brazil, were identified. A database o leprosy cases was set up linking patients' addresses to 64 urban districts. Leprosy cases were detected in 86% of the districts and three risk strata were identified. The highest-risk area for leprosy was in the outskirts of the city and detection rates increased on moving from more developed to poorer areas. The risk of detecting leprosy cases was 5.3-fold greater (95% CI: 3.8-7.4) in the outskirts of the town than in the central zone. Discussed are the methodological issues related to leprosy case ascertainment, completeness and reliability of information, and the interpretation of the spatial distribution of leprosy per unit area. Highlighted also are the lack of leprosy control activities in primary health care units and the usefulness of geographical analysis in planning health services.

Adolescent↗

[5 leprosy cases in the 20th century in Switzerland].

Leprosy had a great impact on everyday life during the Middle Ages, which is reflected in many works of art and also in some preserved buildings. Worldwide, leprosy is still an unsolved problem; this fact has led the World Health Organization to develop a specific strategy to fight the disease. For physicians in Europe, leprosy has lost its significance. In the archives of the Swiss Canton of Valais leprosy in the 20th century is documented by photographs and written records. It is deplorable to see how a young woman can become crippled, lose her eyesight and die within a couple of years. Probably a pocket of leprosy persisted since the Middle Ages in this remote mountain area. The limited contagiousness of the disease is astonishing, since only a few of the closest family members and inhabitants of the some house were infected, while others remained healthy. The social situation of these patients at the beginning of this century was pitiable. The federal laws on epidemics of 1886 did not mention leprosy, as no one seemed to believe in its existence in Switzerland. Even after the cases of leprosy in the Canton of Valais were revealed, the reaction of the political authorities was reserved. An engaged effort by the involved physicians was necessary to establish the appropriate hygienic measures. In the literature of the time there were regular reports of cases in people who emigrated from the endemic areas. Today, in Switzerland one case of leprosy is discovered per year; thus, leprosy is still a disease which physicians must cope with.

History, 19th Century↗

Leprosy today.

Leprosy is a disease common to developing countries. It is relatively rare in Europe. There are an estimated 5.5 million patients in the world, of which two-thirds are found in South East Asia. Currently, 3.1 million are registered for treatment. Mycobacterium leprae, the causative organism of leprosy, is an intracellular acid-fast organism not cultivable in vitro. The disease is transmitted from man to man mainly through inhalation. The disease occurs in several types depending upon the immunological status of the individual. They are generally grouped into two main categories, multibacillary and paucibacillary. The diagnosis of leprosy, which is generally not difficult, is based on characteristic skin lesions, sensory loss, thickening of the nerve trunks and the presence of acid fast organisms in the skin smears. Complications in leprosy include reversal reaction and erythema nodosum leprosum. Currently, the treatment of leprosy is based on the administration of a combination of drugs, referred to as multidrug therapy, which for multibacillary leprosy is treatment with rifampicin, clofazimine and dapsone and for paucibacillary treatment with rifampicin and dapsone. The treatment of complications such as reversal reaction and erythema nodosum leprosum essentially involves the use of prednisolone. Multidrug therapy has been found to be highly effective in curing leprosy and in preventing relapse, although the duration of treatment is still considered long. The optimistic situation in leprosy treatment has led to WHO establishing a target of eliminating leprosy as a public health problem by the year 2000, defining elimination as attaining a level of prevalence below one case per 10,000 population.(ABSTRACT TRUNCATED AT 250 WORDS)

Developing Countries↗

Strategies for improvement of management of ocular complications in leprosy.

Responsibility for eye care of leprosy-affected persons should be shared between leprosy and eye care staff. Leprosy and PHC staff should be responsible for: treatment of reversal reactions in the face, and of recent lagophthalmos, with prednisolone, conservative treatment of mild lagophthalmos, referral of patients with severe lagophthalmos and/or exposure keratitis, unless there is sufficient expertise within the programme, recognition of the acute red eye and treatment of acute conjunctivitis, referral of all other conditions of acute red eye, unless there is sufficient expertise within the programme, recognition of severe visual impairment and referral as needed, recognition of the need for reading glasses in patients aged over 40 years, in rehabilitation services, encouraging medical colleges, Control of Blindness Societies, and staff of general eye care facilities, to actively take part in the treatment of eye complications in patients affected by leprosy, and encouraging charitable organizations to provide special eye care programmes for patients affected by leprosy, in particular for those who are disabled and are living in leprosy settlements. Eye care services (a visiting ophthalmologist or paramedical ophthalmic assistant to the specialized leprosy centres for consultation is an appropriate alternative and may sometimes be even more feasible) should take the responsibility for: eyelid surgery in patients with large lid gaps (> 6 mm), or, signs of exposure keratitis, and treatment and follow-up of acute iritis, corneal ulcers, foreign bodies, and other causes of 'the acute red eye', in cooperation with the leprosy service or PHC staff. The eye care services should offer 'positive discrimination' in the treatment of cataract-blind leprosy patients, realizing the great difficulties that these patients have in avoiding injuries or taking care of injuries once they have occurred, especially in the case of limbs that have lost protective sensation.

Blindness↗

WHO Expert Committee on Leprosy.

Considerable progress has been made in the fight against leprosy during the past 10-15 years, following the introduction of multidrug therapy (MDT) regimens and the establishment of the goal of eliminating leprosy as a public health problem by the year 2000. Current estimates indicate that there are about 1.15 million cases of leprosy in the world, compared with 10-12 million cases in the mid-1980s. This report presents the conclusions of a WHO Expert Committee convened to review the global leprosy situation and the technology available for eliminating the disease, to identify the remaining obstacles to reaching the goal of eliminating leprosy as a public health problem, and to make appropriate recommendations for the future on technical and operational matters. The current status of leprosy elimination is discussed, and the various antileprosy drugs are reviewed, including the most recently available drugs. On the basis of field trials and clinical studies, the Committee concludes that a single dose of a combination of rifampicin, ofloxacin and minocycline is an acceptable and cost-effective alternative regimen for the treatment of single-lesion paucibacillary leprosy, and that the duration of the current MDT regimen for multibacillary leprosy could possibly be shortened to 12 months. The Committee points out the need for improved management of reactions and neuritis and prevention of leprosy-related disabilities and impairments, and recommends that antileprosy activities should become an integral part of general health services and should involve communities to the fullest extent possible.

Persons with Disabilities↗

Reflections on some aspects of leprosy among children in Brazil and in other countries.

The authors discuss the classification, clinical aspects, lepromin reactivity, and epidemiologic features of leprosy among children. The most frequent characteristics of each form of leprosy are described. Lepromatous leprosy is less frequent among children in countries of low endemicity and more frequent, even in the most advanced forms, in hyperendemic regions. Borderline forms are rare. In a large number of cases the initial manifestations are those of the indeterminate form and, in an even larger number of cases, of the tuberculoid pole. The evolution from indeterminate to the tuberculoid pole very frequently occurs in a few months or within less than one year. With respect to epidemiology, the authors consider the general frequency of leprosy among children and the frequency of each form of leprosy among children and adults. Data from surveys carried out in Brazil and other countries are presented. Children have a potential for the rapid development of immunoresistance and consequently of lepromin-positivity, and therefore only a few of them eventually develop lepromatous leprosy. This explains the low indices of lepromatous leprosy (approximately 5%) even in hyperendemic areas. Finally, they discuss the factors that may be responsible for the clinical manifestations of leprosy and their characteristics among children.

Adolescent↗

Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: preliminary results.

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.

BCG Vaccine↗

Human leukocyte antigen and leprosy: study in northern Louisiana and review.

We examined the relationship of human leukocyte antigen (HLA) phenotype to leprosy in six sporadic cases in northern Louisiana and in the world literature through pooling of the results of several studies. We found that HLA antigens DR2 and DQwl were associated with leprosy in the six cases in northern Louisiana (relative risks, 4.57 for DR2 and 4.53 for DQwl), but the results are not statistically significant. We pooled the Louisiana study and other population studies of HLA and leprosy. The results of the pooling show DR2 and DQwl to be associated with leprosy (relative risks, 2.65 for DR2 and 2.73 for DQwl), and these associations are highly statistically significant (P less than 1 x 10(-8) for DR2 and P = 3.6 x 10(-8) for DQwl). Further, we pooled studies of lepromatous leprosy patients vs. controls and studies of tuberculoid leprosy patients vs. controls and found that DR2 and DQwl are associated with both the lepromatous and the tuberculoid forms of leprosy and that these associations are statistically significant. We consider the associations of DR2 and DQwl in these population studies to be evidence for an HLA-associated genetic influence on susceptibility to leprosy.

Adult↗

Treatment of leprosy: science or politics?

OBJECTIVE: To review the history of the treatment of leprosy and leprosy reactions after World War II. METHODS: Treatments based on experience and clinical evidence are compared with those advised by the WHO in their quest to eliminate leprosy by the year 2000, later extended to 2005. RESULTS: Leprosy is not eliminated. Analyses of data on reaction treatment suggest that the treatment regimens for leprosy reactions as advised by the WHO may lead to more impairment among leprosy patients than the 'old' established regimes. CONCLUSION: WHO policies to eliminate leprosy may have jeopardized the proper treatment of leprosy for years to come.

Attitude to Health↗

The mycobacterial secreted antigen 85 complex possesses epitopes that are differentially expressed in human leprosy lesions and Mycobacterium leprae-infected armadillo tissues.

The granulomatous skin lesions in leprosy are thought to be initiated by the immune response to certain antigens of the causative agent, Mycobacterium leprae. The antigen 85 complex is one of the major targets in the immune response to M. leprae infection. In the present study, a panel of previously characterized monoclonal antibodies (MAbs) (3A8, Rb2, A4g4, A2h11, Pe12, and A3c12) reacting with different epitopes of the 85 complex proteins of Mycobacterium tuberculosis and M. leprae was employed in a comparative immunohistological analysis to demonstrate the in situ expression of 85 complex antigenic epitopes in leprosy lesions across the clinical spectrum and in M. leprae-infected armadillo liver tissues. These MAbs showed a heterogeneous staining pattern in a given leprosy lesion. In highly bacilliferous borderline and lepromatous leprosy lesions, MAbs Rb2, A4g4, A2h11, and Pe12 stained clear rod-shaped M. leprae bacilli within macrophages, and the degree of staining correlated with the bacillary index of the lesion. On the other hand, MAbs 3A8 and A3c12 staining was mostly seen as a diffuse staining pattern within interstitial spaces and on the membranes of the infiltrated cells but not the bacilli. In paucibacillary borderline and tuberculoid leprosy lesions, only 3A8, Rb2, and A3c12 showed distinct staining in association with infiltrates in the granuloma. None of these MAbs showed any detectable reaction with control nonleprosy skin lesions, while MAb A3c12 positively stained the granulomas of both leprosy and control specimens. In situ reactivity of these MAbs with M. leprae-infected armadillo liver tissues also showed a heterogeneous staining pattern. Interestingly, a clear difference in expression of these epitopes was observed between armadillo tissues and human leprosy lesions. By immunogold ultracytochemistry, we further showed the differential localization of these MAb-reactive epitopes on the cell surface, in the cytosol, and at the vicinity of M. leprae within Kupffer cells of armadillo liver tissues. Our results indicate that these antigenic epitopes of the antigen 85 complex are differentially expressed in leprosy lesions and infected armadillo tissues and that they could be target determinants in the immunopathological responses during M. leprae infection.

Animals↗

Indeterminate leprosy: a seroimmunological and histochemical evaluation.

An effort was made to differentiate indeterminate (IND) leprosy from other types of the paucibacillary (PB) group of leprosy and to identify among indeterminate leprosy cases those which may evolve to multibacillary (MB) leprosy, using serological, immunological and histochemical parameters. A total of 92 untreated, histologically classified (TT-19, BT-30, IND-32) patients, including 11 cases diagnosed as nonspecific dermatitis (NSD), which were clinically strongly suspected to be leprotic, were screened for antibodies against PGL-I, 35-kDa and LAM antigens. Lepromin tests and antigen demonstration in tissue by indirect immunoperoxidase staining were also carried out. Though a qualitative analysis did not differentiate, a quantitative analysis in terms of a cumulative index (CI) showed a higher antibody level amongst the indeterminate group of patients than the other groups included in PB leprosy. Also, the lepromin negative indeterminate group patients showed a higher CI than the lepromin positive cases, indicating that perhaps these may be the cases which may develop into MB leprosy. Thus, the semiquantification of antibody levels in the form of a CI may be a useful parameter to predict the possible evolution of a given case of indeterminate leprosy. Interestingly 64% of NSD cases had either antigen or antibody which indicated that they were probably cases of leprosy.

Antigens, Bacterial↗