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PubMed1996

[Initial manifestation of tuberculoid leprosy in pregnancy. Guidelines for diagnosis and therapy].

Pregnancy has long been associated with the first presentation of clinical leprosy or aggravation of the existing disease. In Germany leprosy has been diagnosed in 107 patients since 1980. A 27-year-old Singhalese female, gravida 2 at 14 weeks' gestation was admitted with well defined, elevated, erythematous lesions on her cheeks and nose. Clinical examination revealed central anaesthesia in the lesions. No further signs of leprosy in the skin, the mucosae and the peripheral nerves were found. Fite-Faraco staining of the skin biopsy showed sporadic acid-fast bacilli and confirmed an active subpolar tuberculoid leprosy (TTs). Outpatient treatment was immediately initiated with oral rifampin 600 mg monthly and dapsone 100 mg daily. During the 4-month treatment cycle the skin lesions vanished completely. Additional leprosy reactions did not occur and the medication was well tolerated. However, in the 32nd gestational week the patient was readmitted with premature labour and 3 weeks later Caesarean section was performed because of cardiotocographic pathology. Polymerase chain reaction (PCR) for M. leprae of placental tissue was negative. Antibodies against phenolic glycolipid 1 (PGL 1) of M. leprae (IgM-Elisa and Dot-Elisa) from cord blood, maternal and newborn blood were not found. On the fifth postpartal day the healthy mother and her baby were discharged. In conclusion, leprosy in pregnancy can be treated safely and successfully by combined drug therapy.

Adult↗
PubMedDate not supplied

Delineating disease: self-management of leprosy identities in South India.

The national and international agencies working to eliminate leprosy are also dominant in setting the boundaries of official discourse on the issue. Within these boundaries the disease is commonly represented as a medical problem with negative social consequences, and it is believed that both problem and consequences will be resolved if leprosy is eliminated and its victims treated and (if necessary) reintegrated within their social groups. For those affected by leprosy the issues are frequently different, elimination in some respects representing a problem as much as a solution. Against this background, which I describe with reference to a group of leprosy-affected people in South India and their position vis- -vis leprosy organizations, I explore some of the contexts in which leprosy patients actively manage their own situations, often in defiance of prevailing development orthodoxies. I conclude that closer observation and analysis of the strategies patients use to manage their disease status have important policy implications.

Anthropology, Cultural↗
PubMed1989

Nongranulomatous involvement of the bone marrow in lepromatous leprosy.

Bone marrow involvement in lepromatous leprosy has been characterized histologically by a proliferation of foamy histiocytes containing lepra bacilli, the so-called Virchow cells. The authors have studied three patients with biopsy-proven lepromatous leprosy in whom Fite stain, performed on histologic sections of bone marrow aspirates, demonstrated numerous bacilli lying free in the interstitium in the absence of Virchow cells or focal collections of foamy macrophages. Two of the patients had a recent diagnosis of lepromatous leprosy by skin biopsy; the third patient had a 33-year history of lepromatous leprosy that had been treated. Bone marrow aspirates were performed in all three patients for evaluation of anemia. The findings indicate that the bone marrow may act as a reservoir for viable organisms in the absence of a host response in treated and untreated patients with lepromatous leprosy. The persistence of viable organisms in the bone marrow in patients with lepromatous leprosy may account for the high rate of relapse and/or recrudescence of the disease following cessation of specific therapy. Bone marrow examination with the Fite modification of the acid-fast stain is therefore indicated in such patients to evaluate bone marrow involvement and the efficacy of treatment.

Adult↗
PubMedDate not supplied

Selective primary health care: strategies for control of disease in the developing world. V. Leprosy.

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

BCG Vaccine↗
PubMed1997

A case-control study of the effectiveness of BCG vaccine for preventing leprosy in Yangon, Myanmar.

BACKGROUND: Five randomized trials, a follow-up study, and six case-control investigations of BCG vaccine's effectiveness (VE) for preventing leprosy have been conducted internationally, with widely varying estimates of VE. Because of the difficulty of generalizing from disparate results, local estimates of VE are needed for health planning purposes and are currently particularly relevant, given the World Health Organization's (WHO) goal to eliminate leprosy by the year 2000. METHODS: We conducted a case-control study in Yangon, Myanmar. Residents of Yangon between the ages of 6 years and 24 years who were listed in the National Leprosy Registry as being on active treatment for leprosy between December 1992 and April 1993 were eligible to participate in the study as cases. Control subjects were matched to the cases on age, sex, and neighbourhood. RESULTS: One or more doses of BCG were associated with a VE of 66%. The results show a significant trend of increasing VE with increasing number of BCG doses (one dose, VE = 55%; two doses, VE = 68%; three doses, VE = 87%). One dose of BCG vaccine appeared to provide protection substantially higher than that found in an earlier vaccine trial in Myanmar, but consistent with results from case-control studies in other countries. CONCLUSIONS: These data suggest that BCG reduces the risk of leprosy in Myanmar, and that BCG vaccination of infants, along with early case-finding and treatment, should be considered an important part of the leprosy intervention strategy.

Adolescent↗
PubMed1998

Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test for infection with the leprosy bacillus.

BACKGROUND: Mycobacterium leprae (M. leprae) soluble antigen (MLSA) reagents have been developed with the aim of finding a reagent, comparable to tuberculin, which could identify individuals infected with the leprosy bacillus. They have yet to be evaluated fully in human populations. METHODS: More than 15000 individuals living in a leprosy endemic area of northern Malawi were skin tested with one of five batches of MLSA prepared using two different protocols. The main difference in preparation was the introduction of a high G centrifugation step in the preparation of the last three ('second-generation') batches. RESULTS: The prevalence of skin-test positivity (delayed-type hypersensitivity (DTH)) and association with the presence of a BCG scar were greater for first (batches A6, A22) than second (batches AB53, CD5, CD19) generation reagents. The association of positivity with M. leprae infection was investigated by comparing results among known (household) contacts of leprosy cases, and among newly diagnosed leprosy patients with those in the general population. While positivity to 'first-generation' antigens appeared to be associated with M. leprae infection, positivity to later antigens was unrelated either to exposure to leprosy cases or presence of leprosy disease. There were geographical differences in the prevalence of DTH to the various batches, probably reflecting exposure to various mycobacteria in the environment. CONCLUSIONS: Our results suggest that the 'second-generation' batches have lost antigens that can detect M. leprae infections, but that they retain one or more antigens which are shared between M. leprae and environmental mycobacteria. Natural exposure to these both sensitizes individuals and provides natural protection against M. leprae infection or disease. Identification of antigens present in these groups of skin test reagents may assist in production of improved skin test reagents.

Adolescent↗
PubMed2002

Disappearance of leprosy from Norway: an exploration of critical factors using an epidemiological modelling approach.

BACKGROUND: By the middle of the 19th century, leprosy was a serious public health problem in Norway. By 1920, new cases only rarely occurred. This study aims to explain the disappearance of leprosy from Norway. METHODS: Data from the National Leprosy Registry of Norway and population censuses were used. The patient data include year of birth, onset of disease, registration, hospital admission, death, and emigration. The Norwegian data were analysed using epidemiological models of disease transmission and control. RESULTS: The time trend in leprosy new case detection in Norway can be reproduced adequately. The shift in new case detection towards older ages which occurred over time is accounted for by assuming that infected individuals may have a very long incubation period. The decline cannot be explained fully by the Norwegian policy of isolation of patients: an autonomous decrease in transmission, reflecting improvements in for instance living conditions, must also be assumed. The estimated contribution of the isolation policy to the decline in new case detection very much depends on assumptions made on build-up of contagiousness during the incubation period and waning of transmission opportunities due to rapid transmission to close contacts. CONCLUSION: The impact of isolation on interruption of transmission remains uncertain. This uncertainty also applies to contemporary leprosy control that mainly relies on chemotherapy treatment. Further research is needed to establish the impact of leprosy interventions on transmission.

Adolescent↗
PubMed2004

Inequality and leprosy in Northeast Brazil: an ecological study.

BACKGROUND: Leprosy is an important public health problem in many developing countries and many features of its determinants are still obscure. METHODS: To investigate whether the incidence of leprosy is related to certain environmental and socioeconomic determinants, an ecological study was undertaken in 165 municipalities of the state of Ceará, Brazil. Social, economic, education, sanitation, demography, meteorology, and health data were collected. The dependent variable was the average incidence rate of leprosy from 1991 to 1999. Simple and multiple linear regressions were performed to assess the relationship between the dependent and the independent variables. RESULTS: The average incidence rate for all the municipalities for the 1991-1999 period, varied from 0.06 to 14.68 per 10000 persons per year. The level of inequality (beta = 1.67, P = 0.011), the mean years of study among the population >or=25 years old (beta = 1.35, P < 0.001), the population growth from 1991 to 1996 (beta = 0.02, P = 0.007), the percentage of children 7-14 years old that did not go to the school (beta = 0.02, P = 0.028), and the presence of a railroad in the municipality (beta = 0.45, P = 0.038) were found to be predictors of the incidence rate of leprosy in Ceará. CONCLUSION: Our findings fit the assumption that, in Ceará, leprosy is associated with a high level of poverty and uncontrolled urbanization. We put forward the hypothesis that urbanization increases not only social inequality eventually leading to strong polarization, but also excludes people from social and material opportunities. Apparently, such deprivations render them susceptible for leprosy.

Adolescent↗
PubMed1988

Comparison of synthetic antigens for detecting antibodies to phenolic glycolipid I in patients with leprosy and their household contacts.

Three synthetic antigens related to the natural antigen phenolic glycolipid I (PGL-I) were compared for their efficacy in detecting leprosy when used as antigens in an enzyme-linked immunosorbent assay (ELISA) for IgM antibody to PGL-I. Absorbance values for ELISAs using the three antigens correlated well (.79 less than r less than .99) and had a high rate of agreement (89.5% less than a less than 98.4%). Of three subjects (household contacts of patients with leprosy) who later developed the disease, one with lepromatous and one with indeterminate leprosy were seropositive by ELISAs using the three antigens before the clinical onset of disease; one who developed borderline tuberculoid leprosy was seronegative. The predictive value of a positive result for the test was very low (less than 2.4%) and the predictive value for a negative result was high (greater than 99.9%) because of the low prevalence of leprosy in French Polynesia (1.78 per 1000). The high sensitivity, specificity, and efficiency of the tests using the three antigens confirmed their great value for serodiagnosis of leprosy, especially the multibacillary form; the ELISA using NTP seems to be more specific and sensitive for detecting the paucibacillary form.

Antibodies, Bacterial↗
PubMed2002

Chromosomal aberration, micronucleus and Comet assays on peripheral blood lymphocytes of leprosy patients undergoing multidrug treatment.

To evaluate the genetic damage in leprosy patients, we carried out the alkaline Comet assay and chromosomal aberration (CA) and micronucleus (MN) tests in peripheral blood lymphocytes of 50 leprosy patients receiving multidrug treatment (MDT) and 50 healthy individuals. The Comet assay showed statistically higher mean values for length to width ratios of DNA mass (P < 0.01) and for mean frequencies of tailed cells (P < 0.001) in cells of leprosy patients than in those of controls. Similarly, the mean frequencies of micronucleated cells (per 1000 cytochalasin B-induced binucleated cells) were significantly greater (P < 0.001) in leprosy patients (19.92 +/- 2.564) than in controls (1.6 +/- 0.231). A statistically significant 10-fold increase in the frequency of CAs (11.16 +/- 0.411) was observed in leprosy patients compared with controls (1.28 +/- 0.242). In multiple regression analyses, when patients and controls were considered together, disease factor alone significantly influenced the genotoxicity markers. In the control group, age and alcohol consumption significantly influenced MN and length to width ratios and CA frequency, respectively. However, in MDT-treated leprosy patients none of the other confounding factors (sex, age, smoking and alcohol drinking) significantly affected the extent of genetic damage.

Adult↗
PubMed1998

Anti-neutrophil cytoplasmic autoantibodies in leprosy.

The objective was to evaluate the frequency of cytoplasmic and peripheral antineutrophil cytoplasmic antibodies (ANCA) in patients with leprosy, and to correlate the presence of ANCA with type and disease activity. Consecutive patients with leprosy were assessed clinically, and IgG ANCA were measured by indirect immunofluorescence. The presence of three of the following was used to assess disease activity: reactional state, fever, new cutaneous lesions, erythrocyte sedimentation rate and C-reactive protein. Sixty-four patients were studied and divided according to the Ridley-Jopling classification: of 38 patients with lepromatous leprosy, eight (21%) had perinuclear (p) ANCA and two (6%) had cytoplasmic ANCA. ANCA titres ranged from 1:20 to 1:320. Of six borderline leprosy patients, one (16%) had p-ANCA. All 20 tuberculoid leprosy patients and 65 healthy control subjects had negative ANCA. There was no correlation between ANCA titres and disease activity in positive patients. ANCA, mainly those with a perinuclear pattern, may be present in leprosy, especially in the lepromatous pole. This disease should be added to the spectrum of diseases with ANCA positivity.

Adult↗
PubMed2002

Building national medicine: leprosy and power in Colombia, 1870-1910.

As imperialist nations rediscovered leprosy in their colonial world in the late nineteenth century, Colombian physicians found endemic leprosy in their own country. The medical community was interested in constructing a national medicine to conform to 'universal' science. To medicalize leprosy, doctors provoked fears through exaggerating the number of leprosy sufferers to demonstrate that charity was incapable of dealing with the problem. The government approved laws of compulsory segregation of leprosy patients in the 1890s, while the 1897 international conference on leprosy held in Berlin gave international sanction to isolation. Lepers actively resisted segregation as a violation of their individual rights. Dr Juan de Dios Carrasquilla studied the disease, experimented with sero-therapy to cure it, and claimed that the flea was its agent of transmission. He combatted segregation and proposed instead a hygienic programme to improve environmental living conditions, but his approach was defeated. When the early twentieth century saw the consolidation of the Colombian state, modernization of the country became a national priority. The government started to take control of lazarettos, enforcing segregation of lepers, who were confined within an area circumscribed by a sanitary cordon. This strategy was a failure, since patients resisted segregation.

Colombia↗
PubMed1976

The histopathologic diagnosis of leprosy.

The objective of this paper is to encourage histopathologists to recognize and diagnose leprosy so that it can be treated effectively at the earliest stage possible, before irreversible deformities result. Recognition of the earliest form of leprosy-indeterminate-is emphasized. Histopathologic descriptions are made and illustrated for the principal types of leprosy. Emphasis is placed on (1) the need for dependable acid-fast staining of leprosy bacillus, (2) the non-specific infiltrate in indeterminate leprosy, and (3) the involvement of nerves in all types of leprosy.

Biopsy↗
PubMed1976

Recent advances in experimental leprosy.

Within the last 15 years we have learned to identify Mycobacterium leprae, determine its viability, screen the efficacy of antileprosy drugs, and monitor the bacilli for drug sensitivity. We have evidence that subclinical infections occur frequently among contacts of patients with leprosy and that the different manifestations of leprosy reflect differences in resistance to M leprae. We are developing hypotheses about the mechanism of these differences. We have experimentally transmitted lepromatous leprosy to normal armadillos, and from these we can obtain amounts of leprosy bacilli which fully substitute for harvests from in vitro cultures. Furthermore, if susceptibility of armadillos can be determined without infecting them and if we can breed them under controlled conditions, we would have an animal model for investigating fundamental and applied areas of leprosy which otherwise are intractable. How much our knowledge has advanced is illustrated by a project of the World Health Organization which calls for the preparation of pure, specific antigens from the now available abundance of leprosy bacilli, which might become valuable as diagnostic and epidemiologic tools and as immunoprophylactic and even immunotherapeutic weapons.

Animals↗
PubMed2005

Co-infection of Mycobacterium tuberculosis and Mycobacterium leprae in human archaeological samples: a possible explanation for the historical decline of leprosy.

Both leprosy and tuberculosis were prevalent in Europe during the first millennium but thereafter leprosy declined. It is not known why this occurred, but one suggestion is that cross-immunity protected tuberculosis patients from leprosy. To investigate any relationship between the two diseases, selected archaeological samples, dating from the Roman period to the thirteenth century, were examined for both Mycobacterium leprae and Mycobacterium tuberculosis DNA, using PCR. The work was carried out and verified in geographically separate and independent laboratories. Several specimens with palaeopathological signs of leprosy were found to contain DNA from both pathogens, indicating that these diseases coexisted in the past. We suggest that the immunological changes found in multi-bacillary leprosy, in association with the socio-economic impact on those suffering from the disease, led to increased mortality from tuberculosis and therefore to the historical decline in leprosy.

Bone and Bones↗
PubMed2004

Clinico-histopathological correlation of skin and nerve in leprosy.

The histopathological features of skin tissue sections in patients clinically diagnosed as leprosy were correlated with the histopathological features of nerve specimens obtained from the same patients. Fifty untreated leprosy patients attending the Outpatient Department of the Department of Dermatology and Sexually Transmitted Diseases of Smt. Sucheta Kriplani and Kalawati Saran Children's Hospitals, New Delhi, India were included in the study. On correlating the histological features of skin and nerve tissue sections, concordant findings were found in 24 out of the 50 patients (48%) but discordance between the histopathological features of skin and nerve tissue sections were found in 26 out of 50 cases (52%). Of these 26 cases, the nerve tissue histology when compared with the skin histology showed features lower down the disease spectrum in 17 (34%) cases. Seven of the 50 patients (14%) showed histological features of leprosy higher in the disease spectrum in the nerve tissue sections than in the skin biopsy sections. One patient clinically LL leprosy demonstrated histopathological features of Histoid leprosy in the skin sections and LL in the nerve sections. The remaining one patient had features of TT leprosy in the skin tissue sections while the nerve tissue histopathology showed non-specific changes. Histological features of the skin tissue sections were consistent with the clinical diagnosis in 33 out of 50 cases (66%). When the clinical groups were correlated with the histological features of the nerve tissue sections, concordance was found in 30 of the 50 cases (60%). On comparison of the histological features of skin and nerve tissue sections with the clinical diagnosis, concordance was still lower i.e., 19 out of 50 cases (38%). Thus the histological features of the skin tissue sections correlated more frequently with the clinical diagnosis than did those of the nerve sections. The importance of neural histology lies in the fact that it shows a higher BI and a lower histological grading in some cases and if not performed the lapse can result in inadequate treatment, drug resistance and even relapse.

Histocytochemistry↗
PubMed2005

Leprosy in a renal transplant recipient: a case report and literature review.

Leprosy is rarely seen in organ transplant patients; only ten cases of leprosy in organ transplant recipients have been reported. We herein report a Taiwanese renal transplant recipient concomitantly infected with borderline lepromatous leprosy. A 68-year-old male received renal transplantation at Guilin, China, in 2000, and then received immunosuppressive therapy with prednisolone, tacrolimus, and mycophenolate. Three years after transplantation, multiple erythematous tender nodules and plaques over the face and lower limbs developed. Biopsies and histopathological examination confirmed the diagnosis of leprosy. We treated the patient with a multidrug regimen including dapsone, clofazimine, and rifampine since November of 2003 with a good response. Unfortunately, he suffered from a cluster of complications after an accidental fall, finally leading to septic shock and death five months later. In summary, we report a rare case of new-onset leprosy after renal transplantation in Taiwan and suggest leprosy should be listed in the differential diagnosis of unusual skin manifestations in organ transplant patients.

Aged↗
PubMed2006

The expression of RAGE and EN-RAGE in leprosy.

BACKGROUND: Extracellular newly identified RAGE-binding protein (EN-RAGE) is a ligand of the receptor for advanced glycation endproducts (RAGE) and has been termed S100A12. The ligation of EN-RAGE with RAGE on the endothelium, mononuclear phagocytes and lymphocytes triggers cellular activation with the generation of the key proinflammatory mediators interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha. OBJECTIVES: The aim of this study was to investigate the presence of RAGE and EN-RAGE, their spatial localization and their coexpression in leprosy lesions. METHODS: Immunohistochemistry and confocal laser scanning microscopy were used to evaluate the expression of RAGE and EN-RAGE in leprosy. By enzyme-linked immunosorbent assay, RAGE and EN-RAGE were detected in the serum. RESULTS: (1) In the multibacillary (MB) and paucibacillary (PB) groups, the level of RAGE production was significantly higher than in patients with atypical mycobacterial infection or sarcoidosis (P < 0.01). In the MB group, the production of RAGE was higher than in the PB group (P < 0.01), and it was higher in patients without the lepra reaction than in patients with the lepra reaction (P < 0.05). (2) In MB, PB and atypical mycobacterial infection, the level of EN-RAGE production was significantly higher than in sarcoidosis (P < 0.01). (3) In the confocal laser scanning microscopic examination, the RAGE and EN-RAGE proteins were detected in lepromatous leprosy. These proteins are spatially colocalized along the cell surface, which is in agreement with their receptor-ligand interaction. (4) A comparable amount of EN-RAGE was detected in the serum of the MB and PB groups. Patients with the reaction showed a higher level of EN-RAGE than patients without the reaction in leprosy. CONCLUSIONS: Our data suggest that in leprosy, RAGE and EN-RAGE may be involved in the proinflammatory process rather than the antimycobacterial activity, especially during the lepra reaction. The blockade of the interaction of RAGE and EN-RAGE at the early stage of the inflammatory process may minimize the inflammatory response and consequent tissue damage or the sequelae of leprosy.

Enzyme-Linked Immunosorbent Assay↗