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PubMed1992

Macrophage and epithelioid cell nuclear morphology in leprosy.

The spectrum of disease in leprosy is characterised by the presence of macrophages in lepromatous lesions and epithelioid cells in tuberculoid granulomas. Since changes in nuclear shape occur during macrophage activation, we have measured nuclear morphology by planimetry in biopsies across the leprosy spectrum. The results show no significant correlation of any of the parameters of nuclear morphology measured between different lesions or between biopsies from the centre and edge of the same lesion. There were no differences between the Ridley-Jopling groups. However, several parameters which measure the degree of ellipticity of the nuclei showed strong correlation with granuloma size in untreated leprosy patients. This suggests that local pressure effects may influence epithelioid cell and macrophage nuclear morphology in leprosy lesions.

Adult↗
PubMed1990

Comparative study of idiotypes on monoclonal antibodies derived from patients with lupus and leprosy and from normal individuals.

A collaborative study was performed to compare the expression of a series of idiotypes defined on human anti-DNA and other autoantibodies. Three panels of human monoclonal antibodies were tested: eight derived from patients with systemic lupus erythematosus (SLE); 13 from an individual with lepromatous leprosy; and 38 from normal subjects. The following rabbit anti-idiotype sera were used: one (RId16/6) raised against the lupus-derived monoclonal anti-DNA antibody 16/6, four (RId8E7, RId4G7, RId4D5 and RIdTH9) against leprosy-derived monoclonal antibodies of various specificities, and one (anti-4.6.3) against a normal-derived anti-DNA monoclonal (KIM 4.6). In addition, two other anti-idiotypes were used--one a murine monoclonal (3I), the other a rabbit polyclonal (RIdD)--which had been raised against polyclonal anti-DNA antibodies from lupus serum. Further experiments were performed with immunoabsorbed fractions of RId8E7. Direct-binding and competition assays were used. All of the anti-idiotypes produced different patterns of positivity among the three panels of human monoclonal antibodies, with the exception of RId8E7 and RId4G7, which showed considerable concordance. There was a tendency towards anti-idiotypes being disease- or group-specific: thus anti-4.6.3 failed to bind to any of the lupus or leprosy-derived monoclonals, while RId16/6 and RId8E7 bound most strongly to the lupus- and leprosy-derived antibodies respectively. KIM 4.6 itself was bound only weakly by RId16/6, while 16/6 was not recognized by anti-4.6.3; 16/6 was, however, bound by 3I, while KIM 4.6 was not. 3I bound to several other monoclonals but RIdD, which has been shown to be specific for the anti-DNA fraction of lupus serum, did not bind to any of them. These results indicate that the majority of these anti-idiotype preparations recognize largely separate sets of determinants. The monoclonal antibodies which bind to DNA may be only partly representative of anti-DNA antibodies in the serum of lupus patients.

Antibodies, Anti-Idiotypic↗
PubMed2006

A ten-year historic study of paranasal cavity endoscopy in patients with Leprosy.

UNLABELLED: Leprosy is an infectious condition that has a chronic evolution caused by the Mycobacterium leprae. It very often attacks the nasal cavities mucosa independent of its clinical form, even before skin lesions or lesions to other parts of the body arise, in the presence or not of clinical complaints. AIM: To show the efficiency of nasal endoscopy to identify endonasal mucosa lesions and the importance of the Otorhinolaryngologist in the diagnosis and follow-up of Leprosy patients. STUDY DESIGN: Clinical history study. MATERIAL AND METHOD: A historic study was performed with 173 patient's records without previous treatment from 1990 to 2000 at the Otorhinolaryngology Services, Instituto de Pesquisas Clinicas Hospital Evandro Chagas, Fiocruz. RESULTS: All of the patients showed nasal lesions, 121 with and 52 without clinical complaints. DISCUSSION: Nasal cavities endoscopy exam enabled early identification of the mucosa alteration in Leprosy patients as well as how to identify the evolution of the lesions. This type of exam also helps to establish local treatment. CONCLUSION: The evaluation and follow-up of Leprosy patients by the Otorhinolaryngologist in a multidisciplinary team are justified and offer the patient early diagnosis and specific treatment.

Biopsy↗
PubMed1992

Leprosy of the larynx.

The result of a study conducted on 30 patients of lepromatous leprosy regarding laryngeal involvement is presented. The incidence of leprous laryngitis is 36.6 per cent in this part of India in lepromatous leprosy patients. Leprosy is long standing disease so laryngeal lesions developed gradually and may be asymptomatic in some cases while others have been found to have variety of clinical manifestation in form of congestion, infiltration, nodulation, thickening and fibrosis. Anti-leprosy chemotherapy is equally effective on these lesions. A screening survey of laryngeal pathology in such cases should be done periodically.

Adolescent↗
PubMed1993

Protective efficacy of BCG vaccine against leprosy in southern Malaŵi.

This paper describes a matched case-control study to determine the efficacy of BCG vaccine in preventing the occurrence of leprosy in southern Malaŵi, a previously unstudied area. The BCG immunization rate amongst 145 individuals with leprosy was 44.8%, compared to 62.5% in 290 matched controls. The protective efficacy of BCG vaccine against leprosy in this region was estimated to be 63.6%; smallpox immunization had no effect. These findings support the view that BCG vaccine should be considered as a control measure in areas where leprosy is endemic.

Adolescent↗
PubMed1988

Leprosy and immunity: genetics and immune function in multiple case families.

Genetic susceptibility to infection with M. leprae was studied in 10 multiple case families of Australian Aborigines. Of the 87 members available for study, 24 had proven stable clinical leprosy which had been or was still being treated with diamino diphenyl sulphone. Evidence of contact with M. leprae in the remaining 63 members as assessed by ELISA to M. leprae sonicate and phenolic glycolipid (PGL) or by indirect immunofluorescence antibody assay was found in 78%, 64% and 71%, respectively. By contrast, in vitro assays of T cell function (LMAT and LTT) were less reliable indicators of exposure. Evidence was sought for possible linkages between human leucocyte antigen (HLA) or non-HLA genes and four marker phenotypes including clinical leprosy, clinical subtype of leprosy and lymphocyte transformation or leucocyte migration inhibition factor (LIF) production in response to M. leprae antigen. No associations were found with any particular HLA or non-HLA gene. On the other hand, sequential analysis of the data from the 10 families was strongly suggestive of a linkage between HLA haplotype and non-responsiveness to M. leprae as manifest by lack of LIF production but not lymphocyte transformation. The model which best fits the data is for a gene on chromosome 6 in close linkage with the HLA haplotype, with two alleles, autosomal recessive inheritance and penetrance of 90%. On this basis, it can be suggested that disease type (lepromatous leprosy) rather than disease susceptibility may be controlled by genes within or closely linked to the major histocompatibility gene complex.

Antigens, Bacterial↗
PubMed2002

High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy.

Levels of leprosy antigen-induced interferon-gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in 96 leprosy patients with type 1 reactions (T1R) before, during and after a standard 12-week course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy patients with untreated T1R produced significantly more TNF-alpha than leprosy patients without T1R. Median levels of IFN-gamma and TNF-alpha in T1R patients fell during treatment with steroids; however, TNF-alpha levels increased as the steroid dose was reduced. Median IL-10 levels increased throughout the steroid treatment period and were associated strongly with TNF-alpha levels. Patients with high cytokine levels had a poorer recovery of sensory or voluntary muscle nerve function, a higher risk of reactivation of symptoms during steroid treatment, and a higher risk of another episode of T1R within 2 months of completing the steroid regimen. Rapid and effective reversal of the inflammatory process in T1R is critical to prevent permanent nerve damage from T1R and monitoring cytokine levels during treatment may be useful.

Adolescent↗
PubMed2002

Immunotherapy with Mycobacterium vaccae and peripheral blood flow in long-treated leprosy patients, a randomised, placebo-controlled trial.

OBJECTIVE: to evaluate immunotherapy as a means of improving peripheral blood flow in chronic leprosy patients. DESIGN: this was a double-blind, randomised, placebo-controlled, clinical trial. MATERIALS: heat-killed Mycobacterium vaccae 1mg plus 0.02 microg Tuberculin protein per 0.1 ml dose in borate buffer, with saline as placebo. Those studied were 92 long-treated residents of a leprosy centre in Iran, 10 of their healthy children and 10 staff members. Evaluation employed the Perimed PF2, Laser-Doppler Flowmeter, a platinum skin thermistor, and a thermal sensibility tester. METHODS: single intradermal injections of test or placebo were given to 103 patients 18 months before the blinded evaluation. Fingerpulp blood flux was measured in controlled conditions and vasomotor reflexes and skin sensation to touch, pain and heat were evaluated in 45 and 47 patients in the placebo and M. vaccae groups, respectively, and in 20 healthy control persons. RESULTS: Laser-Doppler flux, skin temperature, vasomotor reflexes and sensation were impaired in leprosy patients. Immunotherapy improved (p < 0.05) Laser-Doppler flux, skin temperature and temperature sensation. CONCLUSIONS: immunotherapy, given 18 months earlier, significantly improved blood flow and temperature sensation, in fully-treated, chronic, leprosy patients. The same principles might be employed in other conditions of reduced peripheral blood flow.

Adolescent↗
PubMed1984

[Lagophthalmos and posterior synechiae of the iris during treatment of leprosy with diaminodiphenylsulfone].

Four years after controlled and standardized chemotherapy with diaminodiphenylsulfone (DDS), 316 patients in the leprosarium at Khokana, Nepal were re-examined for ophthalmological findings. Patients who, 4 years earlier, had not had lagophthalmos in either eye, nor posterior synechiae of the iris, had only developed these complications in the meantime if they were suffering from DDS-resistant leprosy. New posterior synechiae of the iris were only found in patients with inactive leprosy who had already had a posterior synechia in the fellow eye four years previously. In cases of inactive leprosy there was also a tendency for existing posterior synechiae to increase. It is emphasized that the development of lagophthalmos or posterior synechiae of the iris indicates that a previously inactive leprosy may have become reactivated in spite of treatment with DDS.

Adult↗
PubMed1988

Learning from lesions: patterns of tissue inflammation in leprosy.

The clinical forms of leprosy constitute a spectrum that correlates closely with the degree of cell-mediated immunity. Patients with tuberculoid leprosy develop strong cell-mediated responses and have only a few, localized lesions, whereas patients with multibacillary lepromatous leprosy are specifically unresponsive to antigens of Myobacterium leprae. T cells of the CD4+ subset predominate in tuberculoid lesions, whereas CD8+ cells predominate in lepromatous lesions. Monoclonal antibodies that distinguish subpopulations of CD4+ and CD8+ cells were used to analyze the distribution of T cells infiltrating lesions across the disease spectrum. In lepromatous lesions, T cells of T-suppressor phenotype (9.3-) were the predominant CD8+ cells and suppressor/inducer cells (2H4+, Leu-8+) represented half of the CD4+ subset. In tuberculoid lesions, helper T cells (CD4+4B4+) outnumbered suppressor/inducer T cells by 14:1, compared with a ratio of 1.2:1 in peripheral blood. Analysis of the precursor frequency of antigen-reactive T cells permitted us to estimate that there was a 100-fold enrichment of T cells able to proliferate in response to M. leprae antigens in tuberculoid lesions (2/100), when compared with blood from the same patients. The methods used here to characterize the T-lymphocyte subsets and frequency of antigen-reactive T cells in leprosy may be useful in analyzing immunological reactions occurring in lesions of other inflammatory and autoimmune diseases.

Antibodies, Monoclonal↗
PubMed2000

Leprosy in China: delay in the detection of cases.

In a national survey in China, 27,928 cases of leprosy detected by the health authorities between 1984 and 1998 were investigated. The delay between onset of symptoms (estimated from each case's recall) and confirmed diagnosis was < or = 2 years for 55.1% of the new patients but > 10 years for 7.0%, with a median value, overall, of 22.0 months. The median delay was longer: (1) for the multibacillary cases than the paucibacillary; (2) among farmers than among factory workers; (3) among some nationalities than among others (being longest among the Tu and shortest among the Wei); and (4) for some methods of case-detection than for others. Over the study period, the mean delay decreased with time. The delay was greatest in the areas where leprosy was endemic and/or where access to health services was poor. The later the cases were detected the more likely they were to show disability. Leprosy cases are still going undetected in China, although, over the last 14 years, case-finding has significantly improved. Age, occupation, nationality, leprosy type and detection method all appear to affect the delay.

Adolescent↗
PubMed1987

Phenolic glycolipid-I of Mycobacterium leprae induces general suppression of in vitro concanavalin A responses unrelated to leprosy type.

Using a costimulant assay, in vitro Con A responses of patients across the leprosy spectrum were found to be markedly suppressed by phenolic glycolipid-I (PGL-I), a unique antigen of M. leprae. The degree of inducible suppression as well as the number of leprosy patients showing suppression of mitogenic responses was higher with PGL-I as compared with integral M. leprae (p less than 0.05 to less than 0.01). Both untreated lepromatous (60%) as well as tuberculoid leprosy (67%) patients showed significant suppression ranging from 13 to 64% and 12 to 79%, respectively. Thus, PGL-I appears to have a universal suppressive effect on Con A responses and is unlikely to play a central role in determining the leprosy spectrum.

Antigens, Bacterial↗
PubMed2002

Local nerve damage in leprosy does not lead to an impaired cellular immune response or decreased wound healing in the skin.

This study investigated whether peripheral nerve damage in patients with leprosy impairs local cellular immune responses, thereby reducing wound healing and leading to chronic skin ulceration. Anesthetic and contralateral sensitive skin sites in 42 patients with leprosy were compared for delayed-type hypersensitivity responses to purified protein derivative (PPD) of tuberculin. Leukocyte recruitment, epidermal activation, keratinocyte proliferation, and rates of wound healing after skin biopsy were compared. No significant differences in PPD-induced induration, epidermal activation and thickening or numbers of total T cells, CD8+ T cells, CD1a+ Langerhans cells, and proliferating Ki67+ keratinocytes were observed between anesthetic and sensitive skin sites. Similarly, rates of wound healing over 5 days after skin biopsy did not differ significantly. Thus, local leprosy-associated anesthesia does not appear to contribute to local immune compromise or impaired wound healing. Rather, chronic cutaneous ulceration in leprosy most likely results from repeated trauma associated with loss of sensation.

Adolescent↗
PubMedDate not supplied

Properties of microorganisms isolated from human leprosy lesions.

Diphtheroids, which in addition to Mycobacterium leprae are present in human leprosy lesions, were identified as true corynebacteria by DNA and cell wall analysis. Peptidoglycan (adjuvant) of these leprosy-derived corynebacteria (LDC) consists of N-acetylglycosaminyl-N-acetyl(glycolyl)-muramic acid and L-Ala-D-Glu(NH2)-(L)-meso-A2pm-(L)-D-Ala (A2pm = diaminopimelic acid). (The amino group of the tetrapeptide is attached to the carboxyl group of the muramate). Peripheral polysaccharide (antigen) is arabinogalactomannan with lateral chains of mannofuranose and arabinofuranose. To the latter are linked mycolic acids containing groups of isomers with 24-36 carbon atoms and containing between zero and four double bonds. DNAs of LDC isolates have a guanine + cytosine content of 56% and demonstrate a high degree of homology. LDC ribosomes cross-react with antisera against mycobacteria and with sera from patients with leprosy. Thermostable antigen M of LDC cross-reacts with the main antigens of tuberculin and lepromin. LDC thus represents a homogeneous and unique group of corynebacteria immunologically related to M. leprae. Leprosy might be the result of a pathogenic cooperation between both organisms, as suggested by the enhancement of M. leprae growth rate promoted in mice by living LDC.

Cell Wall↗
PubMedDate not supplied

Environmental nonhuman sources of leprosy.

Leprosy has been considered to occur only after exposure to a human case. However, evidence has been accumulating that this conventional view is wrong and that an environmental nonhuman source is critical to some human infections with Mycobacterium leprae. Observations, some of which date back to the nineteenth century, support soil, vegetation, water, arthropods, and armadillos (Dasypus novemcinctus) as environmental sources of leprosy. Disparate clinical, epidemiologic, and microbiologic evidence has been critically reviewed in light of the fact that 50%-70% of sporadic cases of leprosy in well-studied populations occur in persons who have had no known contact with human leprosy. Historical data and current information alike substantiate the concept of nonhuman sources of the disease; recent observations with monoclonal antibody have shown that phenolic glycolipid-I antigen, which is unique to the M. leprae cell wall, is present in soil. In the absence of a technique for in vitro cultivation, indirect methods and the body of observations reviewed here persuasively favor but do not prove the existence of environmental nonhuman sources of M. leprae.

Animals↗
PubMed1986

Quantitation of the phenolic glycolipid of Mycobacterium leprae and relevance to glycolipid antigenemia in leprosy.

Chemical and immunologic procedures have been developed for quantitation, in the body fluids of patients with leprosy, of phenolic glycolipid I, the major specific antigen of the leprosy bacillus. Serum samples were extracted with CHCl3/CH3OH and fractionated on columns of silicic acid. Thin-layer chromatography with a sensitivity of about 500 ng allowed detection of the glycolipid in untreated lepromatous and borderline patients, and high-pressure liquid chromatography gave a quantitation of 0.8-3.7 micrograms/ml of serum from four patients. An ELISA-inhibition assay with polyclonal antibodies to glycolipid corroborated these figures. Dot-ELISA on nitrocellulose with polyclonal and monoclonal IgG antibodies allowed for much greater sensitivity (500 pg) and semiquantitative evaluation. Small quantities of glycolipid were present in the urine of patients with lepromatous leprosy. In sera obtained from patients undergoing chemotherapy, the amount of glycolipid declined sooner than did titer of antibody. This experimental approach is applicable to diagnosis of leprosy, bacillary quantification, and standardization of skin-test reagents and vaccines.

Animals↗
PubMed1991

Urinary phenolic glycolipid 1 in the diagnosis and management of leprosy.

A simplified assay to measure the phenolic glycolipid 1 (PGL-1) of Mycobacterium leprae in the urine was applied to the diagnosis of leprosy and the monitoring of antileprosy chemotherapy. One hundred seventy-nine previously untreated patients and 25 normal controls were tested. The specificity of the assay was 100%. There were no false-positive results. The sensitivity of the assay varied with the type of leprosy from 92% for lepromatous leprosy to 56% for borderline lepromatous and 18% for borderline tuberculoid patients. After the onset of chemotherapy in lepromatous leprosy patients, there was often a transient increase of urinary PGL-1, followed by a steady decline. Within 3 months of multiple drug therapy, urinary PGL-1 levels were reduced by 90%-99% and were often undetectable. This assay appears to have considerable potential for monitoring chemotherapy and detecting treatment failure and relapse in patients with Hansen's disease.

Antigens, Bacterial↗
PubMed1995

Prevention and early detection of leprosy in children.

India with its 4 million cases of leprosy, accounts for one-third of the world's population of leprosy patients. One-fourth of them are below 15 years of age. We report a 5-year follow-up study of healthy children who were close contacts of leprosy patients, in order to: 1. detect subclinical infection and observe the development of overt disease by using the Fluorescent Leprosy Antibody Absorption Technique (FLA-ABS) and the lepromin test which assess the humoral and cell-mediated immunity (CMI), respectively; 2. evaluate the efficacy of dapsone as a chemoprophylactic agent in the 'at risk' contacts. Four-hundred-and-fifty-five healthy contacts were studied. Majority of the contacts of multibacillary patients (303) were FLA-ABS positive (75 percent) and lepromin negative (55 percent) showing that although most of them had been infected, the lepromin status was negative (P < 0.01). On the other hand, the majority of the contacts of paucibacillary patients (152) were lepromin positive (57 percent) (P < 0.05). Furthermore, only 61 percent of contacts of paucibacillary patients were FLA-ABS positive as compared to 75 percent of contacts of multibacillary patients demonstrating that the former had been exposed to a lesser quantum of infection (P < 0.05). On the basis of results of FLA-ABS and lepromin tests, these 455 contacts were classified into four groups, viz. Group I comprising children who were FLA-ABS positive and lepromin positive; Group II, who were FLA-ABS positive and lepromin negative; Group III, who were FLA-ABS negative and lepromin positive; and Group IV who were FLA-ABS negative and lepromin negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗