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PubMedDate not supplied

Study of gene probes in childhood leprosy.

The objective was to detect nucleic acids of M. leprae in skin lesions of leprosy patients and study the effect of treatment on these nucleic acids, using r-RNA gene probes, using a cross sectional study. The study was carried out at Department of Paediatrics, S.N. Medical College, Agra and Department of Microbiology, Central JALMA Institute for leprosy, Agra. The study included 32 cases of leprosy less than 16 years of age, divided into 3 groups viz. without treatment (12 cases), in middle of treatment (11 cases) and at the end of treatment (9 cases). All cases were subjected to a detailed history and thorough clinical examination. All of them had smear examination and lepromin test done and their skin biopsies were subjected to gene detection. Nucleic acids were isolated from skin biopsies of all cases by standard procedure. After dot blotting of these nucleic acids, they were hybridised with radioactive (p32) r-RNA probes. The results were interpreted after getting the X-ray films processed with background signals from controls. Majority of cases were between 13-16 years of age. As age advanced, the disease moved from tuberculoid end of spectrum towards lepromatous end (p < 0.05). Majority of paucibacillary (PB) cases were lepromin positive while majority of multibacillary (MB) cases were lepromin negative (p < 0.05). In specimens of untreated cases, 50% of PB specimens and 87.5% of MB specimens were positive for r-RNA probes. In multibacillary type 100% smear positive specimens and 67% smear negative specimens were positive for r-RNA probes. In patients during the middle of treatment positivity for r-RNA decreased and 20% of PB specimens and 16.6% MB specimens were positive. At the end of treatment (1 year for PB cases and 2 years for MB cases), the results of r-RNA were negative, which indicated that the treatment regimens used in the study were effective. This study supports the usefulness of r-RNA probes as a diagnostic and therapeutic tool in childhood leprosy.

Adolescent↗
PubMed1994

[Clinical aspects and therapy of early lepromatous leprosy with a case example].

Taking into account the increase in worldwide human migration, leprosy is of growing importance in the differential diagnosis of dermatological diseases encountered in Central Europe. We report on the case of a young man from Ghana who developed hypopigmented maculae and plaques on his trunk and proximal limbs. The diagnosis of lepromatous leprosy could be made in consideration of the histological pattern of infiltrating leucocytes and detection of numerous acid-fast mycobacteria on skin biopsy. The results of the physical examination as well as routine laboratory and immunological parameters were consistent with this form of leprosy. Due to glucose-6-phosphate-dehydrogenase deficiency, treatment with dapsone was contraindicated. With high-dose rifampicin and clofazimine therapy, the skin changes cleared over the course of 11 months following a leprosy reaction type II (erythema nodosum leprosum) that developed during a phase of discontinued therapy due to low patient compliance.

Adult↗
PubMed2003

Criteria for diagnosis of pure neural leprosy.

The clinical diagnosis of pure neural leprosy (PNL) remains a public health care problem mainly because skin lesions-the cardinal features of leprosy-are always absent.Moreover, the identification of the leprosy bacillus is not easily achieved even when a nerve biopsy can be performed. In an attempt to reach a reliable PNL diagnosis in patients referred to our Leprosy Outpatient Clinic, this study employed a variety of criteria. The nerve biopsies performed on the 67 individuals whose clinical, neurological, and electrophysiological examination findings strongly suggested peripheral neuropathy were submitted to M. leprae identification via a polymerase chain reaction (PCR). Mononeuropathy multiplex was the most frequent clinical and electrophysiological pattern of nerve dysfunction, while sensory impairment occurred in 89% of all cases and motor dysfunction in 81%. Axonal neuropathy was the predominant electrophysiological finding, while the histopathological nerve study showed epithelioid granuloma in 14% of the patients, acid fast bacilli in 16%, and nonspecific inflammatory infiltrate and/or fibrosis in 39%. PCR for M. leprae was positive in 47% of the nerve biopsy samples (n=23). PCR, in conjunction with clinical and neurological examination results, can be a powerful tool in attempting to identify and confirm a PNL diagnosis.

Adolescent↗
PubMed1985

Depression of lymphocyte responses to mitogens in mangabeys with disseminated experimental leprosy.

Mononuclear cells from mangabey monkeys with disseminated experimental leprosy had increasingly severe depression of blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen as the disease progressed. Blastogenic responses were not depressed in cells from mangabeys with more localized disease. Blastogenic responses of cells from normal mangabeys appeared to vary with a circannual rhythm. The demonstration of significant negative correlations between the blastogenic responses to mitogens and the percentages of OKT8+ cells suggested that the mangabey OKT8+ subset may contain cells with suppressor function. The depressed responses to mitogens by cells from monkeys with disseminated experimental leprosy were associated with relatively high percentages of OKT8+ cells. Polyclonal immunoglobulin plaque-forming cell responses to pokeweed mitogen were depressed in cells from experimentally infected mangabeys. The results indicated that defects in immune regulation may occur in experimental leprosy in mangabeys, similar in some respects to the defects that have been reported in human leprosy.

Animals↗
PubMed1983

Demonstration of mycobacterial antigens in nerve biopsies from leprosy patients using peroxidase-antiperoxidase immunoenzyme technique.

Peripheral nerve biopsies from patients with leprosy were stained with anti-Mycobacterium bovis (BCG) in a peroxidase-antiperoxidase (PAP) system to demonstrate intraneural mycobacterial antigens. Most M. leprae antigens have been shown to cross-react with BCG. Of the 30 biopsies from borderline tuberculoid (BT) patients 18 had acid-fast bacilli while 26 of them had demonstrable mycobacterial antigens in their nerves. All borderline lepromatous (BL) and lepromatous leprosy (LL) nerve biopsies had both M. leprae and mycobacterial antigens within them. Most of the antigens in the BT patients were seen to be extracellular. In BL and LL patients antigens were seen both extracellularly and intracellularly in Schwann cells and infiltrating macrophages. Mycobacterial antigens in BT nerves were always seen to be surrounded by a mononuclear cell reaction while in the BL and LL patients antigens could be seen with minimal cellular infiltrate and the neural architecture was more or less preserved. While bacilli could not be seen in BT patients who had been released from treatment for more than 4 years, mycobacterial antigens could still be seen in some patients who had been released from treatment for up to 5 years. Patients with no skin lesions but with large, painful, or tender nerves were found to have intraneural inflammation surrounding mycobacterial antigens, while those with a similar clinical picture but without tender or painful nerves showed no marked inflammation within their nerves despite the presence of mycobacterial antigens. From these findings it was concluded that immunologically mediated inflammatory response toward intraneurally located M. leprae antigens in conjunction with other host factors may be necessary for nerve damage in the BT leprosy patients. In the BL and LL patients the mechanisms of nerve damage are still unknown with certainty but local effects and immune-complex damage secondary to abundant M. leprae antigens are worth exploring. The use of immunohistological techniques should offer a new approach in the study of the immunopathology of leprosy.

Antigens, Bacterial↗
PubMed1989

IgA antibodies against phenolic glycolipid I from Mycobacterium leprae in serum of leprosy patients and contacts: subclass distribution and relation to disease activity.

The anti-PGL-I IgA response against phenolic glycolipid I (PGL-I) a specific surface antigen of Mycobacterium leprae, was demonstrated to be essentially of the IgA1 subclass in sera from leprosy patients and contacts. Anti-PGL-I IgA1 mean levels were found to increase significantly from the tuberculoid toward the lepromatous pole of the leprosy disease spectrum, thus resembling the predominating anti-PGL-I IgM response. Furthermore, anti-PGL-I IgA1 values were shown to increase significantly with increasing bacillary load, measured as bacillary index (BI) from skin biopsies. However, a number of BI negative leprosy patients recorded elevated anti-PGL-I IgA1 levels possibly reflecting a persistence of disease activity. Three of 28 household or family contacts of leprosy patients were detected seropositive for anti-PGL-I IgA1. Thus, our results suggest that anti-PGL-I IgA1 may be considered as an additional parameter for the early detection of infection with M. leprae.

Antibodies, Bacterial↗
PubMed1989

Anti-neural antibodies in leprosy sera: further characterization of the antigens.

Sera or plasmas from 129 leprosy patients were tested by immunoblotting for antibodies that bound to proteins in a Triton-insoluble fraction enriched in neural intermediate filaments (IF fraction) from human or bovine spinal cord. Sixty samples (47%) showed positive staining of proteins at 35 kDa, 42 kDa or both. The presence of these antibodies appeared to be evenly distributed across the spectrum of disease. The frequency of these antibodies in samples from 12 healthy Ethiopians was similar to that in the leprosy group. Similar antibodies were found in only three of 28 samples from U.S. patients with neurologic diseases and in seven of 35 normal U.S. sera. Sera from U.S. tuberculosis patients stained multiple bands in the 50-30 kDa region of the blots; 11 of 16 stained bands corresponding to the 35 kDa or 42 kDa bands along with a number of other bands in this region. The 35 kDa and 42 kDa antigens do not appear to be breakdown products of neural filaments or glial fibrillary acidic protein, since antibodies to these proteins do not react with the 35 kDa or 42 kDa antigen. Further, the staining pattern with the leprosy sera is unchanged following Ca2+-mediated proteolysis of the IF-enriched fraction. The two antigens differ from one another in isoelectric point: the pI of the 35 kDa antigen is 5.9, and the pI of the 42 kDa antigen is 4.8. Staining of the immunoblots with antibodies against a number of known neural antigens failed to identify the 35 kDa and 42 kDa antigens. The 42 kDa antigen appears to be a component of axolemma, since 42 kDa-positive leprosy sera stained a protein with identical migration in preparations of bovine peripheral nervous system and human central nervous system axolemma. In some sera, antibodies reacting with the 35 kDa antigen were adsorbed by D-O bovine serum albumin, a synthetic analogue of the terminal disaccharide portion of the phenolic glycolipid 1 of Mycobacterium leprae. Antibodies to the 42 kDa antigen were not removed by this treatment.

Antibodies↗
PubMed1982

HLA-DR-associated genetic control of the type of leprosy in a population from surinam.

The relationship between HLA phenotype and leprosy classification was studied in 73 unrelated patients and 92 healthy controls from a mixed Negroid-Caucasoid population originating from Surinam, South America. Heterogeneity in the distribution of HLA-DR (but not A, B, and C) was detected between tuberculoid (TT* + BT*) leprosy and lepromatous (BL* + LL*) leprosy patients (p = 0.024). This heterogeneity appeared to be caused almost exclusively by DR3. Most significantly, the frequency of DR3 was increased among polar tuberculoid (TT) leprosy patients as compared to the rest of the patients (p = 0.0003). Compared with healthy controls the frequency of DR3 was increased among TT patients (p = 0.006), unchanged in BT patients, and decreased among lepromatous (BL + LL) patients (p = 0.027). These data indicate that in this population an DR3-associated factor controls the type of the disease that develops after infection with Mycobacterium leprae.

Antigens, Heterophile↗
PubMed2006

Reconstructive surgery of the leprosy nose: a new approach.

There has still been no reduction in the detection rate worldwide for leprosy, despite supervised multi-drug therapy. In time, leprosy can result in a severe saddle-nose deformity leading to functional problems, disfiguration and stigmatization. In severe cases, only the nasal skin tissue and the lower lateral cartilages are preserved. In such cases, the ideal would be to restore the cartilaginous skeleton but, by contrast with other causes of saddle-nose deformities, this is complicated by the quantity and the poor quality of the remaining nasal mucosa. Leprosy-related saddle-nose deformities are therefore challenging and difficult to reconstruct with the techniques that have been proposed in the past. In this study, 24 patients underwent rhinoplastic surgery involving the use of autogenous costal and/or auricular cartilage or composite grafts. The nasal septum, the upper laterals and the anterior nasal spine were reconstructed with a dorsal onlay attached to a columellar strut with an extension on the proximal side. Before surgery, the saddle-nose deformities were classified according to severity with a new system based on clinical symptoms and signs. Postoperative evaluation was performed at least two years after surgery (N=17). Functional and aesthetic improvement, resorption rate, warping, infection and extrusion were analysed. Functional and aesthetic improvements were achieved in 15/17 patients. None of the patients developed an infection and extrusion or warping of the implants was not observed. The resorption rate depended on the localization and the type of cartilage implant. In general, auricular conchal cartilage implant grafts resulted in less resorption than costal cartilage. Least resorption (4/17 patients) was observed in the dorsal onlay grafts of both conchal (1/6) and costal cartilage grafts (3/11). Resorption of columellar strut implants and shield grafts was observed in 7/17 patients. No resorption was seen of composite grafts (0/4) and alar battens (0/7). Autogenous cartilage implants can be used to reconstruct saddle-nose deformities in leprosy with a minimum risk of complications. The preoperative grade of severity was used as a basis for the development of guidelines for optimal long-term functional and aesthetic outcome.

Adolescent↗
PubMed2005

Genetic dissection of immunity in leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that affects an estimated 700,000 new individuals each year. A strong contribution of host genetics to susceptibility to leprosy has long been suggested to account for the considerable variability observed between individuals exposed to M. leprae. As there is no relevant animal model for human leprosy, forward genetics is the main strategy used to identify the genes and, consequently, the immunological pathways involved in protective immunity to M. leprae. With respect to genome-wide screens, a major breakthrough has been reported this year; variants in the regulatory region shared by PARK2 and PACRG have been identified as being common risk factors for leprosy.

Chronic Disease↗
PubMed2007

The oral mucosa in paucibacillary leprosy: a clinical and histopathological study.

BACKGROUND: Involvement of the oral mucosa can occur in lepromatous leprosy; however, lesions in the oral mucosa of paucibacillary patients have not been previously observed. OBJECTIVE: The objective of this study is to determine whether clinical and subclinical lesions exist in oral mucosa in nontreated paucibacillary leprosy patients, using clinical and histopathological examination. MATERIALS AND METHODS: A clinical and histopathological study involving 30 untreated paucibacillary leprosy patients was conducted. All patients underwent biopsies of the buccal mucosa, soft palate, and tongue. When acid-fast bacilli in association with inflammatory infiltrate, granulomatous or not, were encountered, it was considered "specific" involvement of the oral mucosa; and "nonspecific" involvement when the bacilli were not encountered. RESULTS: Eight nonspecific chronic inflammatory reactions and 1 granulomatous inflammatory process without acid-fast bacilli were detected. CONCLUSIONS: Paucibacillary leprosy patients do not exhibit specific, clinical or subclinical, involvement in the oral mucosa; nonspecific alterations occur even in the absence of signs and symptoms.

Adolescent↗
PubMedDate not supplied

Immunogenetics of episcleritis in leprosy.

Human leukocyte antigens (HLA) were analyzed among Japanese leprosy patients to identify any possible determinants in the development of episcleritis in leprosy patients. Seventy-nine Japanese leprosy patients (33 patients with history of episcleritis and 46 patients without episcleritis) and 114 healthy control subjects were investigated. Human leukocyte antigen-class I and class II specificities were determined serologically by the standard microcytotoxicity test. The HLA-DRB1, -DRB5, -DQA1, and -DQB1 genotypings were performed by using the polymerase chain reaction (PCR)-single strand conformation polymorphism and PCR-restriction fragment length polymorphism analyses. The frequency of HLA-Cw3 was significantly increased among the patients with episcleritis (66.7%) compared to patients without episcleritis (43.5%; odds ratio = 2.6, P < 0.05). The frequency of HLA-DR4 was significantly decreased among the patients with episcleritis (15.2%) compared to patients without episcleritis (39.1%; odds ratio = 0.28, P < 0.05) and the controls (46.5%; odds ratio = 0.21, P < 0.001). At the genomic level, frequencies of the HLA-DRB1*0405, -DQB1*0401, and -DQB1*0302 alleles were significantly decreased among the patients with episcleritis (0%, 0%, and 6.1%, respectively) compared to patients without episcleritis (15.2%, 13.0%, and 26.1%, respectively; odds ratio = 0.07, 0.09, and 0.18, P < 0.05). HLA-DRB1*0405 and -DQB1*0401 were also significantly decreased among the patients with episcleritis compared to the controls (29.8% and 29.8%; odds ratio = 0.04, P < 0.0001). Our results suggest that HLA-Cw3 antigen confers the susceptibility to the development of episcleritis among Japanese leprosy patients. Concurrently, the DRB1 (the -DBR1*0405), and/or DQB1 (the -DQB1*0401 and -DQB1*0302) alleles might provide protection against leprous episcleritis.

Alleles↗
PubMed1999

Differential protective effect of bacillus Calmette-Guerin vaccine against multibacillary and paucibacillary leprosy in Nagpur, India.

For this paper we conducted a secondary data analysis to test the hypothesis that a linear trend exists in the protective effect of bacillus Calmette-Guerin (BCG) vaccine against types of leprosy. We used data from two previous case-control studies to perform an unmatched test for linear trend. We observed that both the studies revealed a significant linear trend (P<0.00001). One study that estimated an insignificant protective effect of BCG against paucibacillary leprosy showed a significant departure from linearity. We conclude that, the protective effect of BCG vaccination is differential across severity of leprosy as it brings about a shift in the immune response to a higher level of cell mediated immunity. We recommend that future studies dealing with the protective effect of BCG against leprosy should also conduct an analysis for trend.

Adolescent↗
PubMed1986

Protective efficacy of BCG against leprosy in Northern Malawi.

The effectiveness of a BCG vaccination programme in protecting against leprosy was assessed by case-control and cohort analyses of data from the Lepra Evaluation Project in Karonga District, Northern Malawi. Results indicate that BCG provides at least 50% protection against leprosy in this population and that protection is independent of age, sex, schooling status, or location within the project area. Agreement between these findings and those from a controlled trial in Uganda indicates that BCG is sufficiently effective against leprosy in East and Central Africa to be considered an important element of leprosy control in that region.

Adolescent↗
PubMedDate not supplied

[Leprosy revealed by oedema of the hands].

BACKGROUND: We reported a case of lepromatous leprosy in a Tunisian woman revealed by a potentially misleading clinical picture involving isolated infiltration of the hands. PATIENTS AND METHODS: A 37 year-old woman consulted in October 2000 for bilateral edema of the hands associated with paraesthesia that had been present for one month. Screening for Hansen's bacilli confirmed the diagnosis of multibacillary leprosy. Daily therapy with triple anti-leprosy treatment was initiated. DISCUSSION: The occurrence of edema, which is classically described as a symptom of a reactional state, can occur during the course of leprosy. Where it is a presenting symptom, this unusual heralding sign can be a source of diagnostic error and delay.

Adult↗
PubMed1983

Leprosy in five armadillo handlers.

Five patients with leprosy are presented. Each had had extensive and chronic contact with armadillos. No other potential risk factor for the development of leprosy could be identified. Since the nine-banded armadillo is a known carrier of leprosy in the southern area of the United States, we believe that these patients may have contracted leprosy from infected armadillos.

Adolescent↗
PubMed1987

Leprosy: new insight into an ancient disease.

Patients with leprosy may be classified into two clinical and histopathologic categories. At one end of the spectrum, patients with tuberculoid leprosy have few skin lesions in which organisms can rarely be identified. At the other end of the spectrum, patients with lepromatous leprosy have numerous skin lesions containing myriad bacilli. Because immunologic resistance is associated with this spectrum, the study of leprosy provides a unique opportunity to gain insight into immunoregulatory mechanisms in man. In addition, serodiagnosis to identify early cases and prevention by vaccination are areas of active research. For patient care, a network of Regional Hansen's Disease Centers has been established under the sponsorship of the National Program for Hansen's Disease, Carville, LA. Because the patients are often poor, their receipt of care and medication without cost helps to ameliorate at least one of the burdens imposed by this potentially devastating illness. The program central office may be called at 800-642-2477.

Humans↗
PubMed2001

DNA encoding a single mycobacterial antigen protects against leprosy infection.

The continuing incidence of leprosy infection around the world and the inability of Mycobacterium bovis bacille Calmette-Guérin (BCG) to protect certain populations clearly indicates that an improved vaccine against leprosy is needed. The immuno dominant 35 kDa protein, shared by Mycobacterium leprae and Mycobacterium avium, but not Mycobacterium tuberculosis or BCG, is recognised by >90% of leprosy patients, making it an ideal candidate antigen for a subunit vaccine. Immunization of outbred Swiss Albino mice with a DNA-35 vaccine stimulated specific T cell activation and IFN-gamma production. DNA-35 immunization induced significant levels of protection against M. leprae footpad infection, comparable to that produced by BCG. Therefore, DNA immunization with the 35 kDa antigen is effective against M. leprae infection and genetic immunization with a combination of antigens holds the potential for an improved vaccine against leprosy.

Animals↗