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 793 records · Page 44Linked to original sources
PubMed2000

Immunological cytokine correlates of protective immunity and pathogenesis in leprosy.

The in vitro production of interferon (IFN)-gamma, interleukin (IL)-5, tumour necrosis factor (TNF)-alpha and IL-10 by blood mononuclear cells in response to whole Mycobacterium leprae and polyclonal stimulii of 23 individuals, representing a variety of conditions in relation to exposure/susceptibility to M. leprae, was assayed. In most cases, healthy household contacts of newly diagnosed multibacillary leprosy patients, designated exposed household contacts (EC), showed low-to-undetectable in vitro IFN-gamma production in addition to substantial TNF-alpha production in response to M. leprae. In contrast, peripheral blood mononuclear cells from previously exposed contacts (R) regarded as resistant-to-leprosy released low-to-moderate levels of IFN-gamma together with a mixed cytokine profile resembling a T helper (Th)0-type response. TNF-alpha/IL-10 ratios in response to M. leprae and Concanavalin A were significantly higher in EC than in R contacts suggesting a role for the TNF-alpha/IL-10 ratio in restraining mycobacteria proliferation and spreading early in infection. The cytokine profiles of leprosy patients were taken as reference points. Post-treatment lepromatous leprosy patients secreted relatively high levels of IL-10 in response to M. leprae, whereas one self-cured tuberculoid leprosy patient produced simultaneously high levels of IFN-gamma and TNF-alpha. In addition, the quantitative changes in the cytokines released by peripheral blood mononuclear cells in EC contacts after Bacille Calmette-Guérin (BCG) vaccination were investigated. Vaccination induced amplification of IFN-gamma production with a concomitant decrease in TNF-alpha/IL-10 ratios that resembled the cytokine pattern observed in R contacts. IFN-gamma production was observed in response to both a cross-reactive antigen (Ag 85) and a M. leprae-specific protein (MMP-I), which attests to a BCG nonspecific stimulation of the immune system, thereby casting these antigens as likely candidates for inclusion in a subunit vaccine against leprosy. Finally, a model for protective x pathologic response to mycobacteria is presented.

Adolescent↗
PubMed1993

Study of HLA class II alleles by PCR oligotyping in leprosy patients from north India.

Host factors seem to play an important role in determining the immune response and the differential manifestations of lepromatous (LL) and tuberculoid (TT) leprosy. In order to investigate the role of immunogenetic factors in determining the form of leprosy, the HLA class II alleles of DRB1, DRB3, DRB5, DQA1, DQB1 and DPB1 were studied by a PCR oligotyping technique in 93 patients and 47 healthy controls. DRB1*1501 and DRB1*1502 (two of five tested subsets of the serologically defined DR2) accounted for 81.5% of the multibacillary patients (relative risk 16.3) and 60.7% of the TT patients (relative risk 5.7) compared to 21.3% in normal, ethnically- and geographically-matched controls. The much stronger association of DRB1*1501 with the multibacillary form than with the TT type of leprosy suggests a possible role in the differential immune response to M. leprae antigens. DQB1*0601 was found significantly more often than in controls throughout the leprosy spectrum, while DQA1*0103 was most frequent in the LL group and DQA1*0102 was selectively increased in the borderline lepromatous (BL) patients. On the other hand, DRB1*0701, DQB1*0201 and DQA1*0201 were decreased in the multibacillary leprosy patients (MLP) compared to TT patients and controls, and DQB1*0503 was selectively decreased in TT patients, suggesting that these HLA alleles might play a role in modulating the immune response that determines the form of leprosy that develops in each patient.

Alleles↗
PubMedDate not supplied

Fine needle aspiration cytology of reactions in leprosy.

OBJECTIVE: To define diagnostic cytomorphologic features of reactions in leprosy. STUDY DESIGN: Part-retrospective, part-prospective, single-blind, controlled study of the applicability of fine needle aspiration cytology in the diagnosis of reactions in leprosy. Cytomorphologic features were compared in 42 clinically diagnosed patients with reactions in leprosy with those in a control group of patients with nonreactional leprosy. The study groups included type 1 and type 2 reactions in 35 and 9 patients, respectively. May-Grünwald-Giemsa and Ziehl-Neelsen staining methods were employed. RESULTS: Statistically significant (P < .01) cytomorphologic features of type 1 reaction were the presence of fragments of collagen and elastin; giant cells; giant cells exhibiting elastin phagocytosis; loose, epithelioid cell granulomas; and fibroblasts. Type 2 reaction was characterized in aspirates by the presence of an abundance of neutrophils in a background of lepromatous leprosy (P < .01). CONCLUSION: Criteria that are used in histopathology for the diagnosis of leprosy reactions can be applied satisfactorily to cytologic smears. A good correlation between clinical diagnosis and cytomorphology can be achieved. Multiple-site aspirates from the skin, nerve and lymph nodes are helpful in substantiating the diagnosis.

Adolescent↗
PubMedDate not supplied

Histological changes in the nerve, skin and nasal mucosa of patients with primary neuritic leprosy.

Primary neuritic leprosy (PNL) presents as a peripheral neuropathy with no visible skin patches and skin smears negative for acid fast bacilli. The pathogenesis of PNL is poorly understood. The aim of the study was to document the histological changes in the nerve, apparently normal skin and nasal mucosa in PNL and to study its significance to the pathogenesis of leprosy lesions. The study is based on a cohort of 208 PNL patients registered at the Schieffelin Leprosy Research and Training Centre, Karigiri. All patients had a nerve biopsy, 196 had a skin biopsy and 39 had a nasal mucosal biopsy. The findings reveal that PNL patients exhibit a spectrum of disease histologically in the nerve ranging from lepromatous to tuberculoid leprosy with a significant proportion (46%) manifesting a multibacillary leprosy histology. Findings in the apparently normal skin and nasal mucosa reveal that there are widespread changes due to leprosy in tissues such as the skin and nasal mucosa even when the disease appears clinically confined to a few nerves. PNL may be an early stage in the pathogenesis of the disease before the appearance of skin lesions. The number of nerves enlarged and lepromin status did not give any clue to the nature of underlying disease.

Adult↗
PubMed1993

Renal transplantation in leprosy patients.

We report four cases of leprosy in renal transplant recipients, two of whom had the disease before transplantation and no signs of relapse even in the presence of immunosuppressive drugs. The other two cases presented with lepromatous and borderline (dimorphous) leprosy 5 months and 5 years after transplantation, respectively. The disease of the last patient was controlled with sulfone even in the presence of immunosuppressive drugs, but the mechanism whereby the first patient rapidly developed lepromatous leprosy is unclear, even though he was a home contact of a patient with lepromatous leprosy (his wife). In view of the data presented here, we do not contraindicate renal transplantation in patients with leprosy who frequently suffer changes in renal function. We believe that renal function should be periodically evaluated in patients with borderline and lepromatous leprosy.

Adult↗
PubMed1995

CD4+ T-cell responses to recombinant hsp65 and hsp18 of M. leprae and their trypsin-digested fragments in leprosy: diversity in HLA-DR restriction.

Mycobacterium leprae heat-shock proteins hsp65 and hsp18 have received immense attention as major T-cell target antigens in leprosy. Both of these hsps and their tryptic fragments were characterized for their ability to stimulate CD4+ T cells derived from polar leprosy cases and healthy contacts. The optimal digestion of hsps with trypsin yielded four fragments of hsp65--TDB65-1 (24 kDa), TDB65-2 (18 kDa), TDB65-3 (17 kDa), TDB65-4 (14 kDa)-- and three of hsp18--TDB18-1 (10 kDa), TDB18-2 (5 kDa), TDB18-3 (3 kDa). While all of these tryptic fragments and undigested hsps triggered CD4+ T cells from tuberculoid (TT) leprosy patients and healthy contacts (SI > 2), only two fragments--TDB65-2 and TDB18-3--were found to be stimulatory in anergic lepromatous (LL) leprosy patients (SI = 5.27 and 3.0, respectively). Blocking studies using allele-specific anti-DR monoclonal antibodies revealed multiple HLA-Dr restriction, with DR2 providing the strongest restriction in both TT as well as LL leprosy. These findings indicate that M. leprae hsps and their trypsin-digested fragments are promiscuous and recognizable in the context of diverse HLA alleles, of which DR2 is the most efficient restriction element. The 18-kDa fragment of hsp65 and the 3-kDa fragment of hsp18 are the most versatile fragments that could elicit in vitro proliferation in both polar forms of leprosy.

Antibodies, Monoclonal↗
PubMed1997

Role of polymerase chain reaction in the diagnosis of early leprosy.

For 39 patients suspected of early leprosy, skin biopsies of the lesions were done and bisected. One piece was used for histopathologic examination and the other for polymerase chain reaction (PCR) studies to detect Mycobacterium leprae. The diagnosis of early leprosy was made clinically in 14 patients and by histopathologic study in 26 patients. Acid-fast bacilli were seen in the histopathologic sections of only two patients, and M. leprae were detected using PCR techniques in 11 patients. In one patient the diagnosis of leprosy was made only because of the detection of M. leprae in the PCR study. Since even in endemic countries the profile of leprosy is changing, detection of leprosy lesions in their early stages has become increasingly important. Since the finding of M. leprae is crucial in the confirmatory diagnosis of early leprosy, it is suggested that PCR studies to detect M. leprae be done wherever possible in conjunction with histopathologic examination. It is also recommended that the feasibility and the cost-effectiveness of both of these methods to find M. leprae be evaluated.

Adolescent↗
PubMed1997

Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy.

Genetically determined differences in immune responses to environmental agents may underlie susceptibility to many autoimmune and infectious diseases. Leprosy provides an example of a polarity in the type of immune response made to an infectious agent, and there is evidence that the major histocompatibility complex is genetically linked to leprosy type. It was found that HLA-DR2 is associated with both tuberculoid and lepromatous types of leprosy; however, a variant at position -308 of the promoter of the neighboring tumor necrosis factor (TNF) gene was increased in frequency in lepromatous (odds ratio = 3.0, P = .02) but not tuberculoid leprosy. Some studies have found higher serum levels of TNF in lepromatous than tuberculoid leprosy, and high TNF levels are found in malaria and leishmaniasis, which are also associated with this TNF allele. It is speculated that this association reflects genetic variability in cytokine production, which influences the immune response to and clinical outcome of leprosy.

Adult↗
PubMed1995

Geographic determinants of leprosy in Karonga District, Northern Malawi.

BACKGROUND: Geographical differences in leprosy risk are not understood, but may provide clues about the natural history of the disease. We report an analysis of the geographical distribution of leprosy in Karonga District, a rural area of Northern Malawi, between 1979 and 1989. METHODS: Cohort study of the incidence of leprosy based on two total population surveys. Area of residence was determined using aerial photographs, which allowed identification of households, as well as location of roads, rivers and the lake shore. RESULTS: Incidence rates were between two and three times higher in the north compared to the south of the district, and lowest in the semi-urban district capital. The most obvious environmental difference between these regions is the north's higher rainfall and more fertile soil. There was no overall association between leprosy incidence and population density, although highest rates were observed in the least densely populated areas. Looking at the entire district, incidence rates increased with increasing distance from a main road, but declined with increasing distance from a river or from the shore of Lake Malawi. The negative association with proximity to rivers may reflect the larger number of rivers in the north of the district. Apparent differences in incidence rates between groups speaking different languages reflected confounding by area of residence. CONCLUSIONS: There is a marked variation, not explained by socioeconomic or cultural factors, in the incidence of leprosy within Karonga District. Our results are consistent with a theme in the literature associating the environment, particularly proximity to water, with leprosy.

BCG Vaccine↗
PubMed1994

Cellular and humoral immune responses to recombinant 65-kD antigen of Mycobacterium leprae in leprosy patients and healthy controls.

Cellular and humoral immune responses to recombinant 65-kD antigen of Mycobacterium leprae (rML65) were studied in leprosy patients and healthy contacts from a leprosy-endemic population. Peripheral blood mononuclear cells from a considerable proportion of tuberculoid leprosy patients, healthy contacts and non-contacts showed proliferative response to rML65 in vitro. A strong positive correlation was observed between the responses to rML65 and bacille Calmette-Guérin (BCG) or leprosin A. Addition of recombinant IL-2 (rIL-2) enhanced the proportion of responders to rML65 considerably in all groups of leprosy patients, healthy contacts and non-contacts. Among lepromatous patients this enhancement was more pronounced in the bacterial index (BI)-negative group. These results indicate that the 65-kD antigen of Myco. leprae is a dominant T cell immunogen in our study population. Though lepromatous patients showed poor lymphoproliferative response to rML65, their IgG antibody levels to the same antigen were markedly high. Most of the BI-positive lepromatous patients with elevated anti-rML65 IgG levels did not show T cell reactivity even with the addition of rIL-2. On the other hand, tuberculoid leprosy patients, healthy contacts and non-contacts showed good T cell reactivity but low levels of IgG antibodies to rML65, thus indicating the presence of an inverse relationship between cell-mediated and humoral immune responses to a defined protein antigen of Myco. leprae in humans. A significant proportion of individuals among tuberculoid leprosy patients, healthy contacts and non-contacts showed neither T cell reactivity nor elevated levels of IgG antibody to rML65. However, in most of these subjects, a T cell response to rML65 was demonstrable with the addition of rIL-2. These results are discussed with reference to the immunoregulatory mechanisms occurring during Myco. leprae infection on the basis of differential activation of Th1 and Th2 subsets.

Antibodies, Bacterial↗
PubMed1996

Lepromatous and tuberculoid leprosy: clinical presentation and cytokine responses.

OBJECTIVE: This study analyzes the major clinical characteristics of patients with active leprosy in relation to the in vitro immune response to the T-lymphocyte activator anti-CD3. METHODS: Thirty-eight patients with an established diagnosis of leprosy were classified according to the Ridley and Jopling table. Peripheral blood mononuclear cells from both lepromatous leprosy (LL) and tuberculoid leprosy (TL) patients and healthy controls were used to evaluate lymphocyte proliferation; immunoenzymatic assays were used to evaluate cytokine production (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-gamma). RESULTS: Peripheral blood mononuclear cells from both LL and TL patients displayed blastogenic responses to anti-CD3. The cytokines IL-1 beta, IL-6, IL-10, and IFN-gamma were detected in culture supernatants. Endogenous production of IL-1 beta was significantly higher in cell cultures from patients with the lepromatous form of the disease compared to those with tuberculoid leprosy. Production of IL-6 in response to anti-CD3 was observed in a significantly higher proportion of LL than TL patients (P = 0.0025). Gamma-interferon production did not differ between TL and LL, but a direct correlation was observed between time of multidrug treatment and IFN production in vitro (P = 0.016). Interleukin-10 was detected in culture supernatants of lymphocytes activated by anti-CD3 from both patient groups, but not from healthy controls. CONCLUSIONS: The findings of this study suggest that patients with the two distinct forms of leprosy are capable of responding to a polyclonal T-lymphocyte stimulus such as anti-CD3 and provide evidence suggestive of alterations in the immune responses mediated by cytokines that may contribute to the spectrum of disease and response to treatment.

Adult↗
PubMed2006

S-100 as a useful auxiliary diagnostic aid in tuberculoid leprosy.

BACKGROUND: The diagnosis of tuberculoid leprosy is often difficult on hematoxylin and eosin (H&E) due to the absence of demonstrable nerve destruction. This study evaluates the utility of S-100 staining in identifying nerve fragmentation and differentiation of tuberculoid leprosy from other cutaneous granulomatous diseases. METHODS: Fifty cases of leprosy including 38 borderline tuberculoid (BT), two tuberculoid (TT), and 10 indeterminate leprosy (IL) were studied. Eleven controls of non-lepromatous cutaneous granulomatous lesions were included. S-100 was used for identifying the following dermal nerve patterns: infiltrated (A), fragmented (B), absent (C), and intact (D) nerves. RESULTS: On H&E, only 18/38 (47.4%) BT cases and 1/2 (50%) TT cases revealed neural inflammation. On S-100 staining of BT cases, 28/38 (73.7%) showed pattern B followed by patterns C and A in 8/38 (21.1%) and 2/38 (5.3%) cases, respectively. Both the TT cases showed pattern B. Only intact nerves (D) were seen in all the control cases. S-100 identified nerve damage in 4/10 (40%) IL cases. The patterns A, B, and C had sensitivity, specificity, and positive and negative predictive values of 100% in diagnosing tuberculoid (BT + TT) leprosy. CONCLUSIONS: S-100 is superior to H&E in identifying nerve fragmentation (p < 0.01). It also aids the differential diagnosis of tuberculoid leprosy.

Biomarkers↗
PubMed1991

Pupil cycle time and early autonomic involvement in ocular leprosy.

Ocular complications of leprosy patients often develop insidiously and with few if any symptoms. This study involves measurement of the pupil cycle time (PCT) to evaluate the autonomic nerve system of the iris to determine the presence of subclinical intraocular involvement. The study included 19 lepromatous (LL), 19 borderline lepromatous (BL), and five borderline tuberculoid (BT) leprosy patients and involved 25 healthy volunteers, 10 patients with pulmonary tuberculosis and eight with Duhring disease. The PCT was measured in these groups. In all leprosy groups included in the study the PCT was higher than in the control groups. Moreover, the PCT of the leprosy patients without any intraocular involvement was higher than in the controls. These results show that in the ophthalmic examination of leprosy patients without any symptoms the fact that autonomic nerve system of the eye is affected by the leprosy can often be determined by measuring the PCT.

Adolescent↗
PubMed1997

Ocular involvement in tuberculoid leprosy--a case report.

Leprosy is rarely diagnosed in our part of the world. In our 26-year-old patient, borderline lepromatous leprosy was first diagnosed in 1992 and was treated with Rifoldin, Lemprene and Dapson according to the standard WHO scheme of treatment. Ophthalmic examination showed minor epithelial lesions of the cornea in both eyes, a reduced corneal reflex in the left eye and a scleral leproma nasally and close to the limbus, also in the left eye. In 1995, the patient was examined again and was treated as above for lepromata of the left eyebrow nasally and of both lower legs. Ophthalmic examination revealed conjunctival irritation, anterior uveitis with leprosy pearls on the pupillary margin and secondary glaucoma. The glaucoma was treated with hypotonics, the uveitis was treated with topical cortisone. The intra-ocular pressure normalised and the uveitis improved. Of the two main types of leprosy, lepromatous leprosy and tuberculoid leprosy, our patient had the second, milder form.

Adult↗
PubMed1974

Leukocyte antimicrobial function in patients with leprosy.

Patients with lepromatous leprosy are unresponsive to lepromin skin-test material and possess defective lymphocyte function in vitro, including impaired mitogenesis in response to antigens of Mycobacterium leprae. It has been claimed that their macrophages cannot digest M. leprae in vitro; such a defect could explain both lepromin nonreactivity and impaired lymphocyte function on the basis of failure of the afferent limb of the immune response (i.e., defective macrophage "processing" of M. leprae). The present studies indicate that macrophages from patients with lepromatous and tuberculoid leprosy and from normal donors do not differ in their ability to digest heat-killed M. leprae in vitro, or in their ability to sustain the viability of M. leprae in tissue culture; that monocytes, macrophages, and polymorphonuclear leukocytes of leprosy patients and controls possess equivalent microbicidal activity against Listeria monocytogenes, Escherichia coli, Proteus vulgaris, Staphylococcus aureus, and Candida albicans; and that polymorphonuclear leukocytes from patients with lepromatous leprosy iodinate ingested bacteria normally. Whether the basic immune defect leading to the development of lepromatous leprosy resides in the lymphocyte or in the macrophage remains to be determined. However, the present study shows that phagocytic cells from patients with either principal form of leprosy function normally in a variety of sophisticated tests of antimicrobial function.

Candida albicans↗
PubMed1998

beta 2-Glycoprotein I-dependence of anticardiolipin antibodies in multibacillary leprosy patients.

This study was undertaken to investigate the influence of beta 2-glycoprotein I (GPI) on anticardiolipin antibody (aCL) titration in leprosy. The study group consisted of 140 sera from patients with multibacillary leprosy (46 borderline, 94 lepromatous). The group included newly diagnosed, previously untreated patients, patients under treatment and patients released from treatment. GPI addition enhanced significantly the aCL titres in sera from lepromatous leprosy but not in those from borderline leprosy. Moreover, when the patients were classified according to their bacteriological status, aCL titres were found to be significantly higher in skin smear positive patients compared to bacteriologically negative patients. Thus, the present study demonstrates that aCL in multibacillary leprosy patients are mainly of the GPI-dependent type and emphasizes the importance of GPI addition for aCL titration in leprosy.

Analysis of Variance↗
PubMed2000

Distinct patterns of microvasculature in the cutaneous lesions of leprosy.

This work is an investigation on the microvasculature of the cutaneous infiltrates of leprosy with the immunohistochemical staining of endothelial cells in cutaneous biopsies. Anti-Factor VIII-related antigen antibody (anti-FVIII-ra) and Ulex Europaeus-1 lectin (UEA-1) binding were utilized as endothelial cell markers. Thirty-nine patients grouped according to the Ridley-Jopling classification (14 borderline tuberculoid, 18 borderline lepromatous, 6 lepromatous, and 1 indeterminate leprosy) were selected for this study. Two microvascular architectural patterns could be clearly distinguished: lepromatous lesions presented a dense and tortuous mesh of microvessels among the Mycobacterium leprae-glutted macrophages; whereas the microvessels in the tuberculoid lesions were restricted to the periphery of the granulomas and were not seen among the central epithelioid cells. We were able to distinguish three basic morphological kinds of infiltrate distribution related to the microvessels: micronodules, cords and macronodules. Intensifications of the FVIII-ra immunoreactivity and UEA-1 binding capacity were observed in the endothelial cells of microvessels involved by the inflammatory infiltrate. A distinct cytokine expression profile at the leprosy poles and the role of mast cells in angiogenesis were speculated as factors contributing to these distinct patterns. Growth of the lesion and systemic dissemination of M. leprae in the bipolar spectrum of leprosy may hypothetically be influenced by the vascular-infiltrate relationship. The detection of angiogenesis in the cutaneous lesions of leprosy may bring about alternate and/or additional strategies for leprosy treatment.

Biopsy↗
PubMed2003

Unexplained delayed nerve impairment in leprosy after treatment.

The objective of this study was to examine the clinical signs, symptoms and course of neuropathies in patients with leprosy who after treatment developed nerve impairment, not explained by relapse or reversal reactions. We searched the case-records of leprosy patients, seen between 1985 and 2002 at the department of dermatology at our centre. Included in the study were patients who had developed nerve impairment after treatment of leprosy in the absence of relapse, erythema nodosum leprosum, or reversal reactions, and who were referred to a neurologist. In these patients, we recorded age, onset of leprosy, type of leprosy, treatment of leprosy, signs and symptoms of delayed nerve impairment, results of electrophysiological studies, responses to treatment and course. Included were 14 patients, of whom eight had a (sub)acute multiple mononeuropathy (group I); and six had a slowly progressive multiple mononeuropathy (group II). Patients in group I had limited improvement of nerve impairment after treatment with corticosteroids, and recurrence of symptoms and signs (usually of the motor nerves) when corticosteroids were tapered off. Patients in group II had slowly progressive predominantly sensory nerve impairment. Initially, they had only subjective symptoms, after at least 3 years objective signs became detectable. These patients were not treated with immunosuppressants. Two groups of patients with unexplained delayed nerve impairment could be distinguished. One group had a multiple mononeuropathy resembling reversal reactions with insufficient response to corticosteroids. In these patients, more aggressive and prolonged immunosuppressive treatment should be considered. The aetiology for the neuropathy in the other group remains unclear and further investigations are needed to understand the pathogenesis before treatment recommendations can be given.

Adult↗