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PubMed2001

Renal lesions in leprosy: a retrospective study of 199 autopsies.

In the present work, 199 patients with leprosy who underwent autopsy between 1970 and 1986 were retrospectively studied to determine the prevalence, types, clinical characteristics, and etiologic factors of renal lesions (RLs) in leprosy. Patients were divided into two groups: 144 patients with RLs (RL+) and 55 patients without RLs (RL-). RLs observed in 72% of the autopsied patients were amyloidosis (AMY) in 61 patients (31%), glomerulonephritis (GN) in 29 patients (14%), nephrosclerosis (NPS) in 22 patients (11%), tubulointerstitial nephritis (TIN) in 18 patients (9%), granuloma in 2 patients (1%), and other lesions in 12 patients (6%). AMY occurred most frequently in patients with lepromatous leprosy (36%; nonlepromatous leprosy, 5%; P < 0.01), recurrent erythema nodosum leprosum (33%; P < 0.02), and trophic ulcers (27%; 0.05 < P < 0.10). Ninety-seven percent of AMY was found in patients with lepromatous leprosy, 88% showed recurrent trophic ulcers, and 76% presented with erythema nodosum leprosum. NPS was found in older patients with arterial hypertension, neoplastic diseases, infectious diseases, and vasculitis associated with GN. Most patients with AMY presented with proteinuria (95%) and renal failure (88%). The most frequent causes of death were renal failure in patients with AMY (57%), infectious diseases in patients with GN (41%) and TIN (45%), and cardiovascular diseases in patients with NPS (41%). No difference in survival rates was observed among RL- patients and those with AMY, GN, NPS, or TIN.

Aged↗
PubMed2006

Interventions to address the stigma associated with leprosy: a perspective on the issues.

This paper presents a perspective on stigma as an effect of leprosy. It identifies some of the strengths and weaknesses of current approaches to stigma reduction in leprosy and presents a rationale for considering alternative strategies. It is suggested that models used to explain health behavior in developed societies are inappropriate for explaining leprosy stigma or for developing strategies to address it. The author recommends due consideration of the alternative logic that characterizes cultural belief systems in countries where leprosy is a challenge. Criticism of the common practice of information dissemination as a strategy to address leprosy stigma is defended and the merits and limitations of an integrated health service in India is discussed. The author defends the suggestion that the principal objective of stigma interventions should be "normalization". An example of a Nepalese project based on empowerment theory is given to demonstrate how the transformation of identity from outcast to positive change agent, can effect "normalization".

Health Knowledge, Attitudes, Practice↗
PubMed2001

Update on leprosy in immigrants in the United States: status in the year 2000.

The World Health Organization established a goal in 1991 of "elimination of leprosy as a public health problem by the year 2000." Although prevalence rates of leprosy have decreased in many geographic areas, it is clear that in some countries where leprosy is endemic, such as Brazil and India, this goal will not be reached. Leprosy is rare in the United States, but 85% of detected cases are in immigrants in whom the disease may mimic many common dermatologic and neurological entities, leading to delay of diagnosis. The statuses of polymerase chain reaction analysis, serological testing, and vaccines are reviewed. Effective multidrug therapy and prevention of permanent damage to nerves by early recognition and treatment will help prevent residual disabilities. This update reviews what is known about the pathophysiology and treatment of leprosy. Increased awareness will lead to earlier recognition, diagnosis, and treatment.

Emigration and Immigration↗
PubMed2004

Differential interferon- gamma production characterizes the cytokine responses to Leishmania and Mycobacterium leprae antigens in concomitant mucocutaneous leishmaniasis and lepromatous leprosy.

BACKGROUND: Tegumentary leishmaniasis and leprosy display similar spectra of disease phenotypes, which are dependent on cell-mediated immunity to specific antigens. Diffuse cutaneous leishmaniasis and lepromatous leprosy represent the anergic end of the spectrum, whereas mucocutaneous leishmaniasis and tuberculoid leprosy are associated with marked antigen-specific cellular immune response. METHODS: We characterized and compared the cell-mediated response to Leishmania and Mycobacterium leprae antigens in a patient with an intriguing association of mucocutaneous leishmaniasis with lepromatous leprosy, which are at opposite ends of the immunopathological spectra of these diseases. This was done by performance of skin tests and by assessment of the cell proliferation and cytokine production of peripheral blood mononuclear cells (PBMCs). RESULTS: Strong skin-test reactions and PBMC proliferation were observed in response to Leishmania antigens but not to M. leprae antigens. The stimulation of PBMCs with Leishmania and M. leprae antigens induced comparable levels of tumor necrosis factor- alpha , interleukin-5, and interleukin-10. However, the interferon- gamma response to Leishmania antigens was remarkably high, and that to M. leprae antigens was almost nil. CONCLUSIONS: We found that concomitant leprosy and tegumentary leishmaniasis can produce opposite polar forms associated, respectively, with absent or exaggerated cell-mediated immune responses to each pathogen. This suggests that independent mechanisms influence the clinical outcome of each infection. Moreover, interferon- gamma appears to play a major role in the clinical expression of these intracellular infections.

Animals↗
PubMed1998

Susceptibility to leprosy is linked to the human NRAMP1 gene.

Leprosy is a debilitating infectious disease of human skin and nerves. Genetic factors of the host play an important role in the manifestation of disease susceptibility. The human NRAMP1 gene is a leprosy susceptibility candidate locus since its murine homologue Nramp1 (formerly Lsh/Ity/Bcg) controls innate resistance to Mycobacterium lepraemurium. In this study, 168 members of 20 multiplex leprosy families were genotyped for NRAMP1 alleles and 4 closely linked polymorphic markers. Highly informative haplotypes overlapping the NRAMP1 gene were constructed, and the haplotype segregation into leprosy-affected offspring was analyzed. It was observed that the segregation of NRAMP1 haplotypes into affected siblings was significantly nonrandom. This finding is consistent with the hypothesis that NRAMP1 itself is a leprosy susceptibility locus.

Alleles↗
PubMed1981

Glomerulonephritis in leprosy.

A renal biopsy from a patient with lepromatous leprosy but no history of erythrema nodosum leprosum (ENL) showed histologic, immunofluorescent, and ultrastructural features typical of immune-complex glomerulonephritis. A literature review found reports of 187 renal biopsies from leprosy patients, with glomerulonephritis in 31% of the cases, and a variety of other renal lesions. This accumulated evidence demonstrates that, contrary to widely held opinion, there is no association between glomerulonephritis and a history of ENL. Furthermore, it suggests that glomerulonephritis in leprosy patients has a similar incidence in lepromatous and non-lepromatous cases. These observations have an important bearing on concepts regarding the pathogenesis of immune complex glomerulonephritis in leprosy and the humoral immune mechanisms in patients with leprosy.

Antigen-Antibody Complex↗
PubMed1998

Correlation of quantitative tests of nerve and target organ dysfunction with skin immunohistology in leprosy.

Loss of nociception and hypohidrosis in skin are hallmarks of leprosy, attributed to early invasion by Mycobacterium leprae of Schwann cells related to unmyelinated nerve fibres. We have studied skin lesions and contralateral clinically unaffected skin in 28 patients across the leprosy spectrum with a range of selective quantitative sensory and autonomic tests, prior to biopsy of both sites. Unaffected sites showed normal skin innervation, when antibodies to the pan-neuronal marker PGP (protein gene product) 9.5 were used, with the exception of intraepidermal fibres which were not detected in the majority of cases. Elevation of thermal thresholds and reduced sensory axon-reflex flare responses in affected skin correlated with decreased nerve fibres in the subepidermis, e.g. axon-reflex flux units (means+/-SEM) for no detectable innervation; decreased innervation; and clinically unaffected skin, were 23+/-3.1; 41.2+/-7.3; and 84.5+/-4.0, respectively. Reduced nicotine-induced axon-reflex sweating was correlated with decreased innervation of sweat glands. Where methacholine-induced direct activation of sweat glands was affected, there was inflammatory infiltrate and loss of sweat gland structure. This study demonstrates a correlation between selective nerve dysfunction on clinical tests and morphological changes in skin, irrespective of the type of leprosy, and is the first to show that loss of sweating in leprosy may result either from decreased innervation and/or involvement of the sweat glands. The findings have implications for the selection and monitoring of patients with leprosy in clinical trials which aim to restore cutaneous function.

Autonomic Nervous System↗
PubMed2006

Socioeconomic, environmental, and behavioural risk factors for leprosy in North-east Brazil: results of a case-control study.

BACKGROUND: Brazil reports almost 80% of all leprosy cases in the Americas. This study aimed to identify socioeconomic, environmental, and behavioural factors associated with risk of leprosy occurrence in the endemic North-eastern region. METHODS: A case-control study in four municipalities. CASES: cases of leprosy diagnosed in the previous 2 years, with no other known, current, or past case of leprosy in the household or in the neighbourhood. CONTROLS: individuals presenting for reasons other than skin problems to the health unit where the case was diagnosed and who lived in the same municipality as the case with whom it was matched. For each case four controls were selected. A semi-structured questionnaire was used to collect demographic, socioeconomic, environmental, and behavioural data. A multivariate hierarchical analysis was performed according to a previously defined framework. RESULTS: 226 cases and 857 controls were examined. Low education level, ever having experienced food shortage, bathing weekly in open water bodies (creek, river and/or lake) 10 years previously, and a low frequency of changing bed linen or hammock (>or=biweekly) currently were all significantly associated with leprosy. Having a BCG vaccination scar was found to be a highly significant protective factor. CONCLUSIONS: Except for BCG vaccination, variables that remained significant in the hierarchical analysis are cultural or linked to poverty. They may act on different levels of the transmission of Mycobacterium leprae and/or the progress from infection to disease. These findings give credit to the hypothesis that person-to-person is not the only form of M. leprae transmission, and that indirect transmission might occur, and other reservoirs should exist outside the human body.

Adult↗
PubMed1979

HLA-linked genes and leprosy: a family study in Karigiri, South India.

The evidence for a genetic determination of susceptibility to leprosy is reviewed. To test the hypothesis that an HLA (histocompatibility leukocyte antigen)-linked gene is associated with such susceptibility, the association between the distribution of leprosy within a family and the segregation of HLA haplotypes was investigated among 72 families who lived in Karigiri, Tamil Nadu State, South India. A statistically significant association was found for families in which siblings had tuberculoid leprosy and in which neither parent had leprosy. The findings from the data of this study agree with those of two previous studies carried out among smaller populations is Surinam and Wardha, Maharashtra State, India. Such an agreement suggests that a genetic determinant which is linked to the major HLA locus on chromosome 6 and which is probably recessive affects susceptibility to tuberculoid leprosy in humans.

Alleles↗
PubMed1985

Leprosy in the United States, 1971-1981.

In the period 1971-1981, 1,835 cases of leprosy were reported in the United States; only 10% of these cases were indigenous. Since 1977, the number of new cases reported each year has risen because of an increase in imported cases of disease, a situation reflecting the increased number of refugees and immigrants who have entered the United States from areas endemic for leprosy. Forty-five of the 50 states reported cases. In only 25% of the imported cases were the patients known to have had leprosy at the time of immigration; the remaining 75% were diagnosed in this country. The highest rate of disease onset for this latter group occurred within 12 months after entry into the United States, but cases continued to be reported 10 years after entry. Active refugee resettlement programs have widely distributed persons with leprosy, contacts of diseased persons, and persons from endemic areas throughout the 50 states, a situation necessitating the development of expertise by medical professionals and public health officials in the diagnosis, treatment, and long-term follow-up of patients with leprosy.

Adolescent↗
PubMed1977

Leprosy and cancer: a retrospective cohort study in Hawaii.

We used data collected on a retrospective cohort of 1,123 leprosy patients living in Hawaii between 1940 and 1970, to test the hypotheses that patients with lepromatous leprosy, who have an impairment in their cellular immune response, would have an increased risk for cancer and that patients with tuberculoid leprosy, who are immunologically competent, would have a normal or even a reduced cancer risk from beneficial stimulation of their cellular immune system by exposure to the Mycobacterium leprae organisms. Based on the survival analysis method, the results of the study supported the predicted increase in cancer cases among the lepromatous leprosy patients (19 observed, 12.7 expected; risk ratio = 1.5) and the predicted decrease among the tuberculoid leprosy patients (14 observed, 17.8 expected; risk ratio = 0.8); in both groups, the findings were consistent across the five racial categories of the study. However, none of these differences between observed and expected cases was statistically significant at the 5% level. The study provided no support for the alternate hypothesis that chronic antigenic stimulation by the M. leprae organisms might lead to an increase in tumors of the lymphoreticular system.

Adolescent↗
PubMed1998

Beggars, metaphors, and stigma: a missing link in the social history of leprosy.

Students of leprosy stigma are at odds over its sources, intensity, and current presistence. On the basis of a study of leprosy in Thailand that combined an archival survey with anthropological field-work, the present article offers a different thesis on these issues from those that have been proposed thus far. The thesis suggests that prior to the discovery of a cure for the disease, its sufferers encountered ambivalent rather than severly stigmatizing reactions. Yet the public's selective exposure-mainly to beggars with the disease-paved the way to the perception of leprosy as the epitome of stigmatization and to its transformation into a metaphor for degradation. Progress in the medical treatment of the disease significantly improved patients' social acceptance but also allowed them to keep their illness a secret. Their consequent disappearance from the public eye turned the figurative use of leprosy in the spoken language into the main source of shaping its image. This development contributed to the irrefutability and perpetuation of the negative image, and even to its intensification to the extent of utter divorce from concrete reality. After expounding this thesis, the paper discusses its potential contribution to resolving the disputes over the roots, severity, and persistence of leprosy stigma on the international level.

History, 20th Century↗
PubMed1997

Decreased survival of HTLV-I carriers in leprosy patients from the Democratic Republic of the Congo: a historical prospective study.

In this historical prospective study using sera stored for 22 years, we investigated the effect of HTLV-I infection on survival in a population of leprosy patients in the Democratic Republic of the Congo (formerly Zaire). We also determined the distribution of HTLV-I by subpopulation, age, and gender. Stored sera taken from a population of leprosy patients and controls in 1969 were tested for HTLV-I. Follow-up survival data on these patients were obtained in 1991. The sera collected in 1969 from 520 individuals was used to determine the prevalence of HTLV-I. Included in this number were 328 patients resident in the sanatorium. Survival and other data were available for 327 of these. A multivariate survival analysis using a logistic regression model was performed to evaluate the influence of HTLV-I status, age, type of leprosy, gender, duration of hospitalization, and ethnic group on survival. The overall prevalence of HTLV-I among the 520 individuals in the prevalence study was 34%, with 37.4% in the leprosy group and 25.2% in the control group (p < 0.01). Multivariate analysis using logistic regression showed that females of the Mongo and Ngombe ethnic group taken together were significantly more likely to be infected than the other groups (OR = 3.67, 95% CI: 2.14 to 6.30). A comparison of the death rates directly standardized for age and sex showed that the rate was significantly higher for HTLV-I positive (5.5/100 person-years of observation) compared with HTLV-I negative (3.6/100 person-years of observation). A survival analysis using the Cox model showed a risk ratio of 1.4 (CI: 1.04 to 1.89) for those infected with HTLV-I. An increase in the death rate was associated with HTLV-I infection in leprosy inpatients. The decreased survival associated with HTLV-I infection may result from an increased susceptibility to a variety of diseases.

Adolescent↗
PubMed2006

Detection of antibodies against Mycobacterium leprae culture filtrate protein-10 in leprosy patients.

The prevalence of IgG antibodies against Mycobacterium leprae recombinant culture filtrate protein-10 (rCFP-10) was investigated in serum samples from 56 leprosy patients, 15 tuberculosis (TB) patients, 14 other skin-diseased patients and 20 healthy subjects. On classifying the patients into bacterial index (BI)-positive and BI-negative groups, the assay showed 83.3 % (15/18) sensitivity for detection of BI-positive leprosy patients. On the other hand, the sensitivity for detection of BI-negative patients was 18.4 % (7/38). None of the 15 TB patients and 14 other skin-diseased patients was positive; however, only one out of 20 healthy individuals was positive, indicating that antibody response to culture filtrate protein-10 (CFP-10) was highly specific (98.0 %; 48/49). Statistically, the performance of the CFP-10-based assay was found to be comparable (P>0.05) with that of an anti-phenolic glycolipid-I (PGL-I) antibody-detecting assay. Thus, M. leprae CFP-10 is potentially a specific antigen for measuring antibody response in BI-positive leprosy patients. Being a secreted antigen, CFP-10 may act as a marker for the viability of M. leprae inside the host, and hence its serological potential is worth exploring for application in monitoring the response of patients with BI-positive leprosy (a highly infectious form) during the course of chemotherapy. When comparing the bacteriological and serological results, an agreement of 82.1 % showed that seropositivity to M. leprae CFP-10 corresponded well with bacteriological criteria. Hence, CFP-10 seems to be a suitable antigen for classification of leprosy patients into BI-positive and BI-negative groups.

Ambulatory Care Facilities↗
PubMed1999

A clinical and bacteriological examination of Mycobacterium leprae in the epidermis and cutaneous appendages of patients with multibacillary leprosy.

In the specimens examined at Ryukyu University Hospital, acid-fast bacilli (AFB) were observed in the epidermis, cutaneous appendages and endothelial cells of capillaries. These specimens were taken from non-ulcerating skin lesions of patients with multibacillary leprosies such as LL and borderline lepromatous leprosy (BL). Of the 211 specimens examined, 23 (10.9%) were AFB-positive [AFB (+)] in the above mentioned skin regions. These AFB (+) samples were taken from nine leprosy patients; six cases (17 samples) of LL, two cases (5 samples) of BL, and one case (one sample) of BB. The AFB positive rate [AFB (+)-rate] in the above mentioned skin regions was high in the unmedicated LL sample (50.0%, 7/14) and low in the medicated mid-borderline leprosy (BB) samples (0.0%, 0/10). Particularly in the intraepidermal eccrine sweat duct (acrosyringium), a relatively high number of AFB were observed. The AFB (+)-rate appears likely to be higher in non-ulcering skin lesions with minor inflammation or in lesions with leprosy reaction than typical skin lesions such as papules, nodules, and infiltrated punched out skin lesions. Although the possibility that viable bacilli could be excreted from non-ulcerating skin lesions appeared to be small, these lesions were suspected of being a possible source of infection.

Adult↗
PubMed1982

Leprosy, an overview.

Leprosy is both a public health problem and a model for host-parasite relationship. There is much progress in many areas, and in most, hurdles are not only scientific but also social and financial. The following are goals to reach: 1) progress of growth of M. leprae in animals (to be able to breed armadillos in captivity or to substitute them with other animals); 2) to develop methods for in vitro culture of M. leprae; 3) to obtain antigens from M. leprae and characterize them immunologically; 4) to achieve techniques for objective diagnosis of infection with M. leprae and of leprosy (these techniques will most likely be serologic); 5) to develop methods to direct and manipulate immune response. This should include a better definition of immunologically active cells, their characterization by reliable methods, and an understanding of their functions. Immune control mechanisms and ways to channel them should also be understood; and 6) to have better methods of treatment including flexible adaptable schedules. It will be clear that "solving" the problem of leprosy requires "solving" the social problems in developing countries, as well as unraveling the mystery of the precise control of immune response. As I pointed out, the problems that we face are basically similar to those of autoimmune disorders and of cancer immunology. Research in autoimmune diseases or cancer might provide answers to questions posed by leprosy. It may also be that research in leprosy could supply answers to questions concerning cancer and autoimmunity.

Animals↗
PubMed1994

Localized lepromatous leprosy and its response to chemo-immunotherapy.

BACKGROUND: This is an unusual presentation of lepromatous leprosy (LL) in a young boy, 12 years of age. The study forms part of a large scale immunotherapeutic trial with Mycobacterium w (M.w) antileprosy vaccine. The trial is being conducted in two major hospitals in New Delhi, India. MATERIALS AND METHODS: This patient presented with three lesions: one on each forearm and the third on the left leg. He was classified initially as borderline tuberculoid leprosy. Slit-skin smears and histopathology from the lesions proved the diagnosis to be lepromatous leprosy with a bacterial index (BI) 6+. The initial lepromin test was negative. The patient was treated with chemo-immunotherapy (standard multidrug therapy and immunotherapy with Mycobacterium w vaccine). RESULTS: Investigations after 1 year (15 months) of multi-drug therapy and three doses of vaccine, showed a remarkable fall in the BI from 6 to 0 in the lesions, a lepromin positivity of 5 mm, and a histological upgrading from lepromatous leprosy to borderline tuberculoid. Immunologic studies at 15 months revealed a good LTT response and high levels of cytokines, specifically IL-2 and IFN-gamma. CONCLUSIONS: This report presents an LL patient with disease limited to a few sites. It stresses the importance of slit-smear and biopsy in all patients of leprosy, and it highlights the upgrading observed on administration of chemo-immunotherapy.

Bacterial Vaccines↗
PubMed1985

Leprosy associated with HLA-DR2 and DQw1 in the population of northern Thailand.

A study of the frequency of HLA-DR2 and DQw1 was performed in leprosy patients and controls in northern Thailand. HLA-DR2 was found in 100% (17/17) of patients with sporadic tuberculoid leprosy and in over 90% (30/32) of all tuberculoid leprosy patients, as compared to 62% (20/32) of controls (p = .02). These strong associations had relative risks of 21.4 for sporadic and 7.4 for all tuberculoid leprosy, and etiologic fractions of 1.0 and 0.84, respectively. There was also a statistically significant and strong association between tuberculoid leprosy and DQw1. These data add to the growing body of evidence that products of HLA class II determinants or closely linked genes may play a role in determining the clinical manifestations of M. leprae infection.

Adult↗