Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LEPROSY”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,405 records · Page 78Linked to original sources
PubMed2000

Leprosy.

Leprosy is a unique infectious disease with a prolonged incubation period and a predilection for skin and nerves. The involvement of nerves by the primary infection as well as the immunologically mediated reversal reactions result in impairment of nerve function and severe disabilities. The introduction of the World Health Organization Multi Drug Therapy over the last two decades has produced dramatic changes in the management and control programmes of leprosy. A recent important contribution to the understanding of leprosy pathogenesis has been the elucidation of the molecular basis for the entry of Mycobacterium leprae into the Schwann cell and the peripheral nerve. Leprosy still remains the commonest cause of peripheral neuropathy in developing countries.

Humans↗
PubMed2006

Olfactory dysfunction in leprosy.

Leprosy (Hansen's disease) is associated with a high incidence of nasal pathology. Despite this fact, the influence of this disorder on the sense of smell is poorly understood. In this study, we administered a standardized 12-item odor identification test to 77 patients with three types of leprosy: tuberculoid (n = 9), borderline (n = 42), and lepromatous (n = 26). All three types exhibited significantly lower test scores than their respective age-, sex-, and smoking-habit-matched controls. Patients with lepromatous leprosy exhibited significantly lower test scores than those with the other two types. Only patients with lepromatous leprosy exhibited meaningful improvement in smell function after treatment. No association between disease duration, per se, and the severity of the olfactory deficit was present. Overall, 100% of the patients exhibited olfactory dysfunction, suggesting that earlier prevalence estimates based on nonstandardized olfactory testing have underestimated the prevalence of this problem.

Adult↗
PubMed1994

Th1-Th2 paradigm: insights from leprosy.

The mechanism by which T cells and cytokines regulate immune processes in skin can be investigated by studying patients with leprosy. The disease, caused by the obligate intracellular bacterium Mycobacterium leprae, forms a spectrum. At one pole, patients with tuberculoid leprosy are able to restrict the growth of the pathogen and their skin lesions are characterized by a predominance of CD4+ T cells and type 1 cytokines including interleukin 2 and interferon gamma. At the opposite pole, patients with lepromatous leprosy are unable to contain the infection and their skin lesions are characterized by a predominance of CD8+ T cells and type 2 cytokines including interleukins 4 and 10. A key determinant of the T-cell cytokine response may be interleukin 12, which selectively favors expansion of CD4+ T cells producing interferon gamma. By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to devise specific immunologic interventions in diseases of skin.

Cytokines↗
PubMed2004

Immune profiling of leprosy and tuberculosis patients to 15-mer peptides of Mycobacterium leprae and M. tuberculosis GroES in a BCG vaccinated area: implications for development of vaccine and diagnostic reagents.

Mycobacterium leprae (ML) GroES has been shown to induce strong T cell responses in tuberculoid as well as in exposed healthy contacts of leprosy patients, and therefore this antigen has been the focus of study as a potential vaccine candidate. Paradoxically, we have shown that ML GroES also induces extremely high titres of IgG1 antibody in leprosy patients across the disease spectrum, a response associated with disease progression. IgG1 antibodies in leprosy also show a negative association with interferon-gamma, a critical T cell cytokine responsible for macrophage activation and intracellular killing of mycobacteria. We therefore queried if antibody and T cell responses were being evoked by different epitopes in ML GroES proteins. To address the issue of epitope recognition in mycobacterial diseases, we have analysed 16 peptides (15-mer peptides) spanning the entire ML and M. tuberculosis GroES protein in leprosy (n = 19) and tuberculosis (n = 9) patients and healthy endemic controls (n = 8). Our analysis demonstrates clearly that the dominant peptides evokingT cell and IgG subclass antibodies were different. The target of both T and B cell responses were cross-reactive epitopes in all groups. Differences in disease and healthy states related to the strength (mean intensity) of the T cell and antibody response. IgG1 and IgG3 antibodies were associated with disseminated disease and IgG 2 and IgG4 with disease limitation. Such comprehensive immune profiling of antigen-specific responses is critical to understanding the disease pathogenesis and also if these reagents are to be exploited for either diagnostic or vaccine purposes.

Amino Acid Sequence↗
PubMed1998

High incidence of IgG antibodies to phenolic glycolipid in non-leprosy patients in India.

Purified phenolic glycolipid (PGL-1) from Mycobacterium leprae was used to detect IgG antibodies against PGL-1 in leprosy patients in an enzyme-linked immunosorbent assay (ELISA). A total of 698 sera were screened; they came from patients suffering from leprosy, autoimmune disease, myeloma, tuberculosis and sexually transmitted diseases (STDs). Cases with miscellaneous diseases and persons undergoing AIDS screening were also included. Sera from lepromatous and tuberculoid leprosy patients gave positivity rates of 60.5% and 41.7%, respectively. In non-leprosy cases, the PGL-1 ELISA showed an overall positivity rate of 6.9%; this was greatest in patients with tuberculosis (43.8%) followed by autoimmune diseases (40.9%) and miscellaneous cases including liver diseases (37.9%). This study emphasizes that PGL-1 ELISA has a low predictive value for diagnosis of active infection by Mycobacterium leprae. Positive reactions in a significant percentage of patients with autoimmune disease are intriguing and need indepth study.

Adult↗
PubMed1990

Giant nerve abscesses in leprosy.

Two leprosy patients with neuritis caused by giant abscesses involving almost the entire ulnar nerve are described. One patient, who also had skin lesions, was diagnosed histopathologically as having borderline tuberculoid leprosy both on skin and nerve biopsy, and the other, with only nerve involvement, belonged to the pure neuritic group. The lepromin test was strongly positive (with a vesicular reaction in one patient) and lymphocyte transformation to Mycobacterium leprae antigen was raised. These lesions can be easily mistaken for a peripheral nerve tumour in places where leprosy is uncommon. A brief account of the management of nerve abscess in leprosy is given.

Abscess↗
PubMed1990

A complex component modulating immune-deficient cells in leprosy patients leading to loss of viability of Mycobacterium leprae--a possible vaccine.

Macrophages from peripheral blood of leprosy patients, both multi-bacillary and paucibacillary are unable to kill phagocytosed Mycobacterium leprae due to their inability to produce superoxide (O2-) and hydroxyl radicals (OH.). The macrophages from healthy individuals are able to kill M. leprae along with release of O2- and OH. radicals. The deficiency in the macrophages of both types of leprosy patients is removed by activation of these cells when exposed to a culture supernatant obtained after stimulation of peripheral blood mononuclear cells from the same patients with delipidified cell components of M. leprae which are most likely cell wall proteins. The activation of macrophages also leads to recognition of whole live M. leprae as an antigen by cells from lepromatous patients. This activation of the phagocytes by delipidified cell components is blocked by cyclosporin A, indicating the possible role of several steps involved in immune activation of cells. The observations thus indicate the significant ability of delipidified cell components to eliminate the deficiencies in the macrophages from leprosy patients and restore them to behave like the cells from healthy individuals. Considering all these, it is suggested that delipidified cell components could be potential modulators, and are probably capable of functioning as a vaccine for leprosy.

Adjuvants, Immunologic↗
PubMed1992

Specificity of IgG subclass antibodies in different clinical manifestations of leprosy.

We analysed specific IgG subclasses levels to Mycobacterium leprae sonicate extract (MSE), lipoarabinomannan B (LAM) and phenolic glycolipid I (PGL-I) in the sera of leprosy patients with different clinical manifestations. IgG2 was found to be the predominant antibody to MSE regardless of clinical manifestations, and IgG1 response was mostly seen in lepromatous patients. IgG3 reacted only rarely but IgG4 reacted relatively more in certain clinical groups such as borderline lepromatous and lepromatous with erythema nodosum leprosum (ENL) reaction. Most of the IgG subclass responses to MSE could be accounted for reactivity with LAM, suggesting that LAM is the major immunogen involved in the pathogenesis of leprosy. In contrast to LAM, PGL-I antigen showed considerably lower reactivities for IgG subclasses. An association between IgG subclass responses and clinical manifestations of leprosy was also seen. Whereas borderline lepromatous patients were found to have significantly higher levels of IgG2 and IgG4 to MSE, lepromatous patients had elevated levels of IgG1 and lower levels of IgG2. An interesting observation, however, was the significantly higher levels of IgG2 to LAM in the pure neuritic leprosy patients.

Analysis of Variance↗
PubMed1994

Nerve and skin damage in leprosy is associated with increased intralesional heat shock protein.

Leprosy is frequently complicated by the development of reversal reactions in which peripheral nerve and skin lesions become inflamed and irreversible nerve damage may ensue. Increased expression of proteins belonging to the 70-kD heat shock family (hsp 70) occurs in cells of the central nervous system exposed to hyperthermia, physical damage or drug-induced trauma. In the present study we have used immunocytochemical staining to monitor hsp70 levels in peripheral nerves infected by Mycobacterium leprae. Hsp70 was detected in skin and nerve lesions from all leprosy patients, but was particularly prominent in lesions from patients undergoing reversal reactions. Hsp70 immunocytochemistry can thus be used as a marker of neural injury in the peripheral as well as in the central nervous system. The cellular dynamics of nerve damage in leprosy are currently poorly understood, and we postulate that the immunopathology of leprosy may be partly due to an autoimmune response to heat shock proteins.

Biopsy↗
PubMed1977

Hormonal changes associated with testicular atrophy and gynaecomastia in patients with leprosy.

Basal LH, FSH, 17 beta-oestradiol and testosterone and the gonadotrophin responses to luteinizing hormone releasing hormone (LHRH) were studied in male patients with leprosy (twenty-four with lepromatous and six with tuberculoid leprosy). The mean basal LH and FSH was significantly elevated in the lepromatous group and was associated with an excessive response of both gonadotrophins following LHRH administration. The mean basal testosterone and 17 beta-oestradiol values in the lepromatous group were significantly lower than those of the tuberculoid and control groups. The abnormal gonadotrophin and sex steroid values in the lepromatous group are in keeping with the testicular atrophy and gynaecomastia accompanying this form of leprosy. However, the lack of a significant correlation between basal FSH and testicular atrophy should be noted. In addition, no correlation between any of these hormonal values and gynaecomastia could be demonstrated. The patients with tuberculoid leprosy had essentially normal hormonal profiles (except for two who had raised 17 beta-oestradiol values). This is compatible with the lack of gonadal involvement in these patients.

Adolescent↗
PubMed2004

Differential production of interleukin-10 and interleukin-12 in mononuclear cells from leprosy patients with a Toll-like receptor 2 mutation.

Toll-like receptor 2 (TLR2) is a key mediator of the immune response to mycobacterial infections, and mutations in TLR2 have been shown to confer susceptibility to infection with mycobacteria. This study investigated the profiles of cytokines, such as interferon (IFN)-gamma, interleukin (IL)-10, IL-12 and tumour necrosis factor (TNF)-alpha in response to Mycobacterium leprae in peripheral blood mononuclear cells (PBMC) with the TLR2 mutation Arg677Trp, a recently reported polymorphism that is associated with lepromatous leprosy. In leprosy patients with the TLR2 mutation, production of IL-2, IL-12, IFN-gamma, and TNF-alpha by M. leprae-stimulated PBMC were significantly decreased compared with that in groups with wild-type TLR2. However, the cells from patients with the TLR2 mutation showed significantly increased production of IL-10. There was no significant difference in IL-4 production between the mutant and wild-type during stimulation. Thus, these results suggest that the TLR2 signal pathway plays a critical role in the alteration of cytokine profiles in PBMC from leprosy patients and the TLR2 mutation Arg677Trp provides a mechanism for the poor cellular immune response associated with lepromatous leprosy.

Adult↗
PubMed2006

Expression of cyclooxygenase-2, alpha 1-acid-glycoprotein and inducible nitric oxide synthase in the developing lesions of murine leprosy.

Murine leprosy is a chronic disease of the mouse, the most popular animal model used in biomedical investigation, which is caused by Mycobacterium lepraemurium (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to the end of the disease, the granuloma undergoes changes that gradually transform the environment into a more appropriate milieu for the growth of M. lepraemurium. The mechanisms that participate in the formation and maturation of the murine leprosy granulomas are not completely understood; however, microbial and host-factors are believed to participate in their formation. In this study, we analysed the role of various pro-inflammatory and anti-inflammatory proteins in granulomas of murine leprosy after 21 weeks of infection. We assessed the expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the granulomatous lesions of murine leprosy. We found that a pro-inflammatory environment predominates in the early granulomas while an anti-inflammatory environment predominates in late granulomas. No obvious signs of bacillary destruction were observed during the entire period of infection, but nitrosylation products and cell alterations were observed in granulomas in the advanced stages of disease. The change from a pro-inflammatory to an anti-inflammatory environment, which is probably driven by the bacillus itself, results in a more conducive environment for both bacillus replication and the disease progression.

Animals↗
PubMed1978

Gut-associated IgA deficiency in lepromatous leprosy.

Sera, intestinal secretions and intestinal biopsies were collected from twelve biopsy-proved lepromatous leprosy patients with the help of a capsule invented by Roy Choudhury. Sera from another twenty-five proved lepromatous cases were also included. Sera and intestinal aspirates from twenty-five normal subjects and twenty patients with intestinal tuberculosis were also taken as controls. Acid-fast organisms, morphologically resembling Mycobacterium leprae, were detected in the intestinal aspirates of only two leprosy patients. Immunoglobulin levels in their sera and elevation secretions were estimated by the single radial immunodiffusion technique. Significant elevation of serum IgG, IgA and IgM, selective IgA deficiency in intestinal aspirates and flattening of intestinal villi along with mononuclear cell infiltration were conspicuous observations in the leprosy group. On the other hand, the patients with intestinal tuberculosis showed elevation of the IgG level in serum as well as in the intestinal secretions. It was postulated that persistent challenge by M. leprae or its antigens to the IgA immunocytes of the intestinal epithelium might have induced tolerance leading to IgA deficiency and subsequent subtotal atrophy of the intestinal villi in the patients with lepromatous leprosy.

Adult↗
PubMed2006

Evaluation of recombinant serine-rich 45-kDa antigen (ML0411) for detection of antibodies in leprosy patients.

The potential of the recombinant serine-rich 45-kDa antigen (ML0411) of Mycobacterium leprae to aid in detecting M. leprae-specific serum antibodies was assessed by an enzyme-linked immunosorbent assay (ELISA) in leprosy patients and controls comprising of tuberculosis patients, other unrelated skin-diseased patients and healthy individuals from India. All 18 multibacillary (MB) and 18/38 (47.4%) of the paucibacillary (PB) leprosy patients were found positive. None of the controls was positive, yielding complete (0/49) specificity in the series tested here. On the other hand, an anti-phenolic glycolipid-1 (PGL-I) antibody-detecting assay yielded detectable responses in 94.4% (17/18) of MB and 36.8% (14/38) of PB leprosy patients. Only two of 49 (4.1%) controls were positive, giving a specificity of 95.9%. Further, there was a good concordance (agreement of 83.8%; chi(2) = 40.3, P < 0.001; kappa = 0.63) between the two assays. Thus, the 45-kDa-based assay was slightly better than anti-PGL-I antibody-detecting assay. Interestingly, when combining the results of both the assays together for all leprosy patients (MB + PB), the combined sensitivity was significantly higher than that of the anti-PGL-I antibody-detecting ELISA alone (73.2% versus 55.4%; P < 0.05), but not (P > 0.05) compared with the 45-kDa antigen-based assay alone. Similarly, in case of PB patients, using both assays in combination, the sensitivity was significantly higher compared with anti-PGL-I antibody-detecting assay alone (60.5% versus 36.8%; P < 0.05). While adopting the combinatorial approach, the specificity remained invariably high (>95%). In conclusion, the results of the present study indicate that the M. leprae 45-kDa protein is a potent B-cell antigen and may be a useful serodiagnostic reagent.

Antibodies, Bacterial↗
PubMed2006

Pituitary-gonadal hormones and interleukin patterns in leprosy.

The functional status of pituitary-gonadal hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous (LL/BL) and tuberculoid (TT/BT) poles of leprosy were investigated. Gonadotropins [luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and C-reactive protein (CRP) concentrations and erythrocyte sedimentation rate (ESR) were significantly higher in LL/BL leprosy patients than in controls and were not different from controls in TT/BT patients. LH and FSH were positively correlated with IL-1beta, IL-6 and TNF-alpha, and CRP concentrations and ESR. Testosterone plasma levels were significantly decreased in LL/BL patients and not different in TT/BT patients compared with controls. In addition, testosterone levels were inversely correlated with IL-6 and TNF-alpha. Prolactin plasma levels of both LL/BL and TT/BT patients were not different when compared with those of controls. There was a significant positive correlation between IL-6 and TNF-alpha plasma levels and ESR and CRP concentrations. IL-1beta was positively correlated with ESR but not with CRP. The significant correlations between gonadotropins and testosterone and cytokines in leprosy patients suggest that cytokines may have a direct influence at testicular level and may be of pathogenetic significance in leprosy and in other inflammatory states involving reproductive dysfunction.

Adult↗
PubMed1980

Psoriasis and other common dermatoses in leprosy.

The medical records of all 309 leprosy patients who have been under the care of the Government Hospital for Hansen's disease in Jerusalem, Israel during the last 30 years, were surveyed. None of the patients showed clinical evidence of psoriasis on numerous examinations conducted during periods of follow-up of up to more than 4 decades. If this finding proves to be reproducible also in other groups of leprosy patients in other regions of the world, this would suggest that psoriasis is very rare among leprosy patients and that psoriatic subjects might have a natural protection against the development of leprosy. This could possibly be explained as the result of the hyperactivity of the reticuloendothelial and phagocytic systems which seems to be an integral part of the psoriatic constitution.

Adolescent↗
PubMed2005

The development of cutaneous lesions during follow-up of patients with primary neuritic leprosy.

BACKGROUND: Primary neuritic leprosy (PNL) is a rare form of leprosy where the characteristic skin lesions are absent. Investigations of apparently normal skin from the areas of sensory change have revealed microscopic evidence of nerve involvement. Clinical studies have found that a proportion of patients develop visible skin lesions during follow-up. The aim of the study was to perform a clinical and histological analysis of PNL patients who developed visible skin lesions during treatment and follow-up, to gain insight into the pathogenesis of the disease. METHODS: Twenty-nine individuals in a series of 182 PNL patients developed visible skin lesions during follow-up. Analysis of the number, location, histology and time of onset of the new skin lesions in relation to the type and regularity of the treatment regimen were noted. A biopsy from the new skin lesion when available was compared with the nerve biopsy findings at the time of initial diagnosis. RESULTS: Thirty-eight per cent of patients developed a single patch and 28% developed two patches. Over three-quarters of these were on the lower limb (47%) or the upper limb (29%). Sixty-two per cent of patients developed the lesions within 2 years of the onset of symptoms. Patients on regular treatment developed patches earlier than those on irregular treatment or no treatment. A skin biopsy from the new patch revealed borderline tuberculoid leprosy histology in 47% of the patients. CONCLUSIONS: The findings suggest that leprosy primarily affects the nerve and that a neuritic phase precedes the development of visible cutaneous lesions.

Adolescent↗
PubMed1979

The HLA antigens and leprosy in Thailand.

HLA-A and -B locus antigens were determined in 170 unrelated patients with leprosy and 100 healthy controls. There were no statistically significant deviations from expected antigen distribution in patients with any of the various forms of leprosy, though the number of patients studied is relatively small. There were some interesting trends, particularly a possible decrease in the number of tuberculoid patients with A9, and an increase in the proportions of lepromatous patients with B18 and B40. Limited evidence of a genetically controlled pre-disposition to the clinical manifestations of leprosy suggests that further studies with extended typing should be carried out on the HLA haplotype segregation in informative leprosy families. These should provide a clearer indication of the relevance of the HLA (including DR) and possibly of other non-HLA loci to the possible mechanism(s) of disease susceptibility.

Adolescent↗