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PubMed1974

BCG vaccination of children against leprosy: nine-year findings of the controlled WHO trial in Burma.

The leprosy incidence rates so far in the vaccinated and unvaccinated children aged 5-9 and 10-14 years are similar. The BCG-vaccinated children aged 0-4 years at intake had an incidence rate lower than that of children in the control group. BCG vaccination did not protect household contacts or children aged 5-14 years not exposed in the household, and did not influence the distribution of the forms of leprosy in the cases detected. The lepromin reaction in relation to the age at intake was consistently stronger in the vaccinated children than in those of the control group; the younger the age group the more pronounced was the difference, which was only slight in the age group 10-14 years at intake. If the results of the late lepromin reaction are related to the age at onset (when the children are older than at intake), the differences between the BCG and the control groups tend to decrease. It does not seem that the BCG-vaccinated children suffer from a less serious form of leprosy than the nonvaccinated children (most of them nonreactors to tuberculin).

Adolescent↗

PubMed1983

Reversal reaction in lepromatous patients induced by a vaccine containing killed ICRC bacilli--a report of five cases.

Clinico-pathological features of five cases of lepromatous leprosy exhibiting "reversal" reaction with upgrading of lesions following vaccination with ICRC vaccine have been described. Two patients also developed ENL. Associated with the "reversal" reaction, the patients exhibited lepromin conversion. No evidence of fresh nerve lesions was observed in any patient. Besides lepromin conversion, occurrence of "reversal" reaction is yet another evidence of immunogenicity of the ICRC vaccine.

Adolescent↗

PubMedDate not supplied

[Longitudinal study of a population of leprosy patients by the TML (leukocyte migration test)].

This is the report of an experiment of leucocyte migration performed with BCG and Lepromin among three groups of people: - one group of leprotic people; - two groups of witnesses. The first one including people with BBS disease having not received corticoid treatment. The reaction against Lepromin are different, among the leprotic group of people from the non leprotic one. We have noticed in the leprotic group variations with time depending on the kind of treatment. This is a fact very interesting to point out. These findings should be showed right or wrong by other physicians.

Cell Migration Inhibition↗

PubMed1983

Fernandez and Mitsuda reactivity in guinea pigs sensitized with heat-killed Mycobacterium leprae: persistence and specificity of skin reactivity to soluble and particulate antigens.

Guinea pigs were sensitized with 500 micrograms dry weight of heat-killed Mycobacterium leprae, M. tuberculosis H37Rv, M. vaccae, or M. nonchromogenicum suspended in saline. Significant Fernandez (peak swelling at 48 hr) and Mitsuda (peaking at 21 days) reactions were observed when all four groups of animals were skin tested with 10 micrograms of the homologous whole-cell antigen (WCA) preparations one month after sensitization. Some of the guinea pigs were given a booster injection of the homologous suspension three months later and were then retested with the four WCA preparations. The Fernandez (rather than the Mitsuda) reactivity was enhanced by the second immunization and was still substantial when tested eight months after boosting. The Mitsuda-type responses observed 12 months after the primary sensitization peaked earlier than in the first- and four-month tests, regardless of the vaccinating organism. The M. leprae-sensitized guinea pigs produced larger Fernandez skin reactions than those seen in the other three groups of sensitized animals, but there was substantial crossreactivity between M. leprae and M. tuberculosis antigens, as well as somewhat lesser responsiveness in the M. vaccae- or M. nonchromogenicum-sensitized animals skin tested with lepromin. The present study indicates that saline suspensions of heat-killed M. leprae induced a highly persistent state of lepromin hypersensitivity which was quantitatively superior to that observed in animals sensitized with the three other mycobacteria.

Animals↗

PubMedDate not supplied

Immunological properties of M. leprae culture isolates ICRC bacilli: hypothesis on relationship between M. leprae and ML-culture isolates.

The M. leprae-culture isolate, being a culture, is identified by biochemical criteria. Majority belong to either M. avium-intracellulare-scrofulacieum complex, or corynobacterium group. The identification is also determined by serological methods using soluble sonicates. Skin tests with heat-killed suspension often give positive Mitsuda response and hence the isolates are discarded as non-M. leprae. The data on ICRC strains show that Dharmendra type antigen prepared from ICRC bacilli compares very well with lepromin in lepromatous patients. The CMI/DTH tests in mice by FPE and LMI technique have experimentally demonstrated that ICRC bacillus is the first cultivable mycobacterium that can sensitize mice against lepromin. These data also brought out antigenic differences between the ICRC strains. The clinical trial on ICRC vaccine has shown that the ICRC bacilli is immunogenic in Man. The biochemical data on ICRC strain show that they possess DOPA-Oxidase and can express biochemical character of 9/10 similarity index with M. leprae with appropriate substrates in the medium. Thus, the ICRC strains possess both M. leprae and M. avium characters. An hypothesis is proposed to explain these observations--The 'Janus face' of M. leprae--by proposing a relationship between M. leprae and its culture isolates, e.g. ICRC bacilli (1). The M. leprae-culture isolate may by a recombinent of M. leprae with M. avium background (2). The ML-isolate may express the CMI related antigenic determinants corresponding to that of M. leprae in the biopsy (3). The CMI related antigens of whole bacilli in the ML-culture isolate may be inducing type as against only eliciting antigen expressed by M. leprae (4). Recombination may provide immunogenicity as well as 'in vitro' growth potential to the ML-culture isolate (5). Absence or failure to express inducing antigen by M. leprae maybe alternate biological escape mechanism from immune surveillance for survival in vivo, with or without suppressor mechanisms.

Animals↗

PubMedDate not supplied

Immunological studies in leprosy. III-Cutaneous response to antigens in spectrum of leprosy.

Delayed type of hypersensitivity response was assessed in 65 cases of leprosy of different types, and 18 control using lepromin (Dharmendra) and candida antigens. 0.1 ml of antigen was injected intra-dermally and results were recorded after 48 hours. The induration of 5 mm or more was taken as positive for early (Fernandez) reaction in lepromin test, and also for candida reaction. Both types of tests were positive in decreasing order from tuberculoid to borderline type while negative in borderline lepromatous and lepromatous type.

Antigens, Fungal↗

PubMed1983

Preliminary trial of intervention levamisole therapy in persistently bacteriologically positive lepromatous leprosy.

The intervention treatment with the immuno-adjuvant levamisole was given in 14 persistently bacteriologically positive lepromatous cases who had had adequate chemotherapy for over 5 years. There was a temporary conversion of the early lepromin reaction in a majority of the patients with a corresponding improvement in clinical and bacteriological status. However, the lepromin response was short lived. Most patients had become bacteriologically negative at the end of 1 year. No adverse effects due to levamisole therapy were encountered.

Adolescent↗

PubMed1993

Armadillos (Dasypus novemcinctus) as a model to test antileprosy vaccines; a preliminary report.

The efficacy of two candidate leprosy vaccines, BCG and a mixture of BCG and killed Mycobacterium leprae, was tested in 62 armadillos caught in the wild. The abilities of the vaccines to convert lepromin-negative armadillos to a positive reaction were compared with a group of control animals. Both vaccines upgraded subsequent lepromin skin-test histopathology. The conversion results parallel the protection values obtained in some BCG vaccine trials against leprosy in humans. Before conducting expensive human trials with new antileprosy vaccines, it would be worthwhile first to evaluate them in the armadillo model.

Animals↗

PubMed1993

BCG vaccination protects against leprosy in Venezuela: a case-control study.

A total of 64,570 household and other close contacts of about 2000 leprosy cases were screened for eligibility for entry into a trial of a new leprosy vaccine. The screening procedure included a clinical examination for leprosy and for the presence of BCG and lepromin scars. Ninety-five new cases of leprosy were identified, and the prevalence of BCG and lepromin scars among them was compared with similar data from matched controls selected from among those with no evidence of leprosy. The difference in the prevalence of BCG scars in the two groups was used to estimate the protection against leprosy conferred by BCG vaccination. One or more BCG scars was associated with a protective efficacy of 56% (95% confidence limits 27% to 74%). There was a trend of increasing protection with four or more BCG scars, but this was not statistically significant. There was no evidence that the efficacy of BCG varied with age or according to whether or not the contact lived in the same household as a case. The protective effect was significantly higher among males, and was significantly greater for multibacillary than for paucibacillary leprosy.

Adolescent↗

PubMed1996

Prognostic evaluation of cell mediated immunity in leprosy and correlation with clinicopathological status of leprosy patients.

Cell mediated immunity was studied in 50 patients of leprosy and 15 control volunteers, by estimation of peripheral blood lymphocytes (PBL), total rosette forming cells (TRFC) and active rosette forming cell (ARFC) counts in vitro. PBL, TRFC and ARFC counts were slightly but not significantly increased in patients of tuberculoid leprosy (TT) and muculoanaesthetic variant of tuberculoid leprosy as compared to control group. However, gradual decrease in T-cell subsets, occurred in borderline tuberculoid leprosy (BT) as compared to tuberculoid type (TT)-(p < 0.05). Significant decrease in lymphocytes and T-cell subsets was observed in midborderline leprosy (BB), (p < 0.01):borderline lepromatous leprosy (BL), (p < 0.001) and lepromatous subpolar and polar types (LL); (p < 0.001) as compared to control group. Mycobacterium leprae (M.leprae) were positive in BT-(20%); BB-(72.7%); BL-(83.2%) and LL-(100%). Delayed hypersensitivity reactions (DHR) revealed significantly increased lepromin positivity in TT (83.3%) and BT (80%) which decreased in BB (63.6%) and BL (50%). Lepromin test showed anergic state in LL group (28.5% positivity). Dinitrochlorobenzene (DNCB) skin test showed 100% positivity in TT group and controls while gradual significant decrease was observed from BT (p < 0.05) to LL scale (p < 0.001). Leprosy spectrum of Ridley and Jopling scale is directly co-related with inherent cell mediated immune status of the patients which has a significant prognostic role in treatment and long term management.

Adolescent↗

PubMed2004

Molecular mechanisms of MHC linked susceptibility in leprosy: towards the development of synthetic vaccines.

Tuberculoid (TT) and lepromatous leprosy (LL) develop in the human host depending on his ability to trigger a specific cellular immune response(CIR). Different genes have been demonstrated in susceptibility/protection and may explain the forms of leprosy. The major histocompatibility complex (MHC) play an important role. The aim of the study was to explore the contribution of human leukocyte antigen (HLA) DRB1, DQA1, DQB1 and DQ promoter genes in LL Mexican patients. Six families (26 LL, three TT patients and 27 controls) were analyzed; 114 unrelated patients were compared with 204 controls. Class I typing was done by the standard microlymphocytotoxicity and class II typing using PCR-SSOP. Haplotype segregation correlated with specific CIR in vivo and in vitro using lepromin. Haplotype sharing was significantly deviated in the affected sibs (p=0.01). Six healthy sibs were non-responders to lepromin and four of them were DQ1 homozgotes. DQ1 was significantly associated with LL and with non-responders. We set up macrophage activation experiments after infecting these cells with 5x10(6) bacilli to demonstrate if elimination occurred in the context or DQ1. When DQ1 was present on macrophages and on T cells, bacteria were poorly eliminated from the cell (32%) while when absent, 76% of the individuals were able to eliminate the bacilli (p=0.03). DRB1*1501 DQA1*0102-DQB1*0602 (DQ1 subtype) was significantly increased in the patients, indicating its participation in susceptibility. QBP 5.11/5.12 promoter present in the mentioned haplotype, and QAP 1.4, linked to DRB1*1301/02 haplotypes were also associated. Two mechanisms are suggested: the promoter polymorphisms may influence allele expression and thus the amount of peptides presented to the T-cell receptor, leading to a deficient CIR: HLA restriction is important for vaccine design; the way peptides anchor the DRB1*1501 groove may be relevant to the activation of TH1 cells, which contribute to an efficient presentation of peptides inducing a protective T-cell response.

Bacterial Vaccines↗

PubMed1993

The major secreted antigen complex (Ag 85) from Mycobacterium bovis bacille Calmette-Guérin is associated with protective T cells in leprosy: a follow-up study of 45 household contacts.

T cell proliferation and interferon (IFN)-gamma secretion were analyzed in 45 leprosy contacts stimulated with antigen 85 (Ag85), the major culture filtrate antigen from Mycobacterium bovis bacille Calmette-Guérin. All 14 Mitsuda reaction-positive contacts reacted to Mycobacterium leprae and Ag85. Three Mitsuda reaction-negative contacts reacted weakly to M. leprae and Ag85. The other 28 Mitsuda reaction-negative contacts did not react to M. leprae, but 9 reacted to Ag85. Thirty-four contacts were retested 16 months later. Eleven contacts initially positive by the Mitsuda test remained lepromin positive and reactive to M. leprae and Ag85. Fourteen contacts initially negative by the Mitsuda test converted, and all reacted in vitro to M. leprae and Ag85. Finally, 9 contacts remained Mitsuda test-negative, and 7 were unreactive to Ag85. In vitro reactivity to Ag85 at baseline in Mitsuda test-negative contacts was associated with subsequent conversion to lepromin reactivity in 7 of 9 subjects. These data suggest that reactive T cells against Ag85 develop very early during M. leprae infection and that Ag85 is a potentially protective T cell immunogen.

Adolescent↗

PubMed1994

Identification of an antigenic domain on Mycobacterium leprae protein antigen 85B, which is specifically recognized by antibodies from patients with leprosy.

Sixty-three overlapping 15-oligomer peptides covering the 30-kDa protein antigen 85B of Mycobacterium leprae were tested by ELISA to identify epitopes recognized by human antibodies. Serum samples from patients with lepromatous leprosy (LL) reacted mainly with peptides comprising amino acid regions (AA) 206-230, 251-280, and 291-325. Sera of patients with active tuberculosis who responded to the native 30-kDa antigen did not recognize these peptides. The antibody-binding specificity to the defined B cell regions was evaluated in a blind study with 71 serum samples from patients and household contacts living in Ethiopia where leprosy is endemic. The peptide of AA 256-280 was recognized by 88% of LL patients, 15% of patients with tuberculoid leprosy, and none of the contacts. These findings suggest that there are major linear B cell epitopes on the M. leprae 30-kDa protein that are recognized by lepromin-negative LL patients, whereas lepromin-positive patients respond preferentially to conformational epitopes.

Amino Acid Sequence↗

PubMed1990

Cell-mediated and humoral immunity in leprosy in children.

Cell-mediated and humoral immunity were studied in 25 children between 0 and 14 years with leprosy. Cell-mediated immunity was studied in vivo by lepromin and epicutaneous sensitization with dinitrochlorobenzene (DNCB) and T-lymphocytes and their subpopulations (T4 and T8) in the peripheral blood. Humoral immunity was evaluated by B-lymphocyte count and immunoglobulins (IgG, IgM and IgA). Along with complement, component C3 was also measured in the serum. Lepromin (Mitsuda) and DNCB responses were significantly poor in mid-borderline (BB) leprosy. The hematological profile, including T-lymphocytes, their subpopulations, B-lymphocytes, serum immunoglobulins, and C3, were found to be normal in all forms of leprosy. The relatively short duration of disease and the low bacterial load may explain these findings.

Adolescent↗

PubMed1991

T cell response to purified filtrate antigen 85 from Mycobacterium bovis Bacilli Calmette-Guérin (BCG) in leprosy patients.

T cell proliferation and IFN-gamma production of peripheral blood mononuclear cells from 25 healthy controls and 39 leprosy patients were tested against BCG-bacilli and culture filtrate. Mycobacterium leprae and purified antigen 85 (the major secreted 30-32 kD protein antigen) from M. bovis strain BCG. In lepromin negative healthy controls, blastogenesis was low to M. leprae and completely negative to antigen 85. IFN-gamma levels were very low, close to detection limits. In all lepromin positive controls, significant proliferation and IFN-gamma secretion was found in response to M. leprae and antigen 85. In the group of lepromatous leprosy (LL) patients, 25/29 of patients (with either positive (13) or negative (12) lymphoproliferative response to BCG) were unreactive to M. leprae or to antigen 85. Four LL patients with positive T cell response to BCG responded with detectable lymphoproliferative response and IFN-gamma secretion to antigen 85. All tuberculoid (TT) leprosy patients responded to BCG, M. leprae and antigen 85. Hence, T cells from leprosy patients and controls demonstrate a marked parallelism of responsiveness towards whole M. leprae and purified antigen 85 from M. bovis BCG, suggesting strong cross-reactivity between the two species and underlining the biological importance of such secreted antigens.

Antigens, Bacterial↗

PubMed1994

Localized lepromatous leprosy and its response to chemo-immunotherapy.

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

Bacterial Vaccines↗

PubMed1984

Immunological unresponsiveness in leprosy.

The various forms of leprosy form a clinical and immunological spectrum which offers extraordinary possibilities for insight into immunoregulatory mechanisms in man. At one pole, tuberculoid leprosy, patients develop high levels of cell-mediated immunity which ultimately results in killing of bacilli in the tissues, albeit often with damage to nerves. At the lepromatous pole, patients exhibit selective immunological unresponsiveness to antigens of M. leprae. Even though all currently known protein species of M. leprae and BCG are cross-reactive, lepromatous patients unreactive to M. leprae antigens frequently respond strongly to tuberculin. In vitro experiments suggest the existence of lepromin-induced suppressor activity, mediated by both monocytes and T cells. The T suppressor cells have the T8 phenotype of which 50% express the activation markers, Ia and FcR. The one unique species of antigen of the leprosy bacillus is a phenolic glycolipid, and it appears that the TS cells largely recognize the terminal trisaccharide of this unique antigen. Depletion of the TS cells restores in vitro reactivity of lymphocytes to lepromin in a portion of lepromatous patients, and addition of IL-2-containing supernatants partially restores responsiveness to M. leprae antigens. Vaccination of lepromatous patients with a mixture of M. leprae and live BCG restores cell-mediated immunity in the majority of lepromatous patients, and concomitantly reduces the in vitro suppressor activity and number of activated T8 cells. These experiments suggest the existence of stage-of-disease related suppressor cells in leprosy which appear to block the responsiveness of TH capable of responding to either specific or cross-reactive mycobacterial antigens. The mode of action of these TS appears to be the inhibition of production of IL-2 and other lymphokines. Successful immunotherapeutic vaccination appears to overcome this block in the majority of patients.

Antigens, Bacterial↗

PubMed1975

Passive transfer of immunity into leprosy patients by transfusion of lymphocytes and by transfusion of Lawrence's transfer factor.

About 1,200 million viable lymphocytes from normal but lepromin- and tuberculin-positive human beings were transfused in four patients of lepromatous and one of tuberculoid leprosy three times at monthly intervals. Three patients of lepromatous leprosy suffered from erythema modosum, whereas the other two developed severe reaction whenever put on the smallest dose of dapsone. In one patient of lepromatous leprosy, minimal improvement or none was observed, whereas in the remaining three cases of lepromatous and one of tuberculoid leprosy, clinical, bacteriological, as well as histological improvement occurred. Two of the five patients started to tolerate the dapsone during the period of study. The present study indicates that immunotherapy might have a definite role in the management of the disease especially in cases with erythema nodosum. Lawrence factor, prepared from leucocytes of normal donors, was transfused three times into four lepromatous leprosy patients who were intolerant to anti-leprosy drugs. The donors were healthy but were tuberculin and lepromin (Mitsuda) positive. The clinical, histological, bacteriological (morphological index), and immunological assessments of the patients were performed before and 5 months after starting the immunotherapy. In two patients conversion of Mitsuda reaction occurred, but there was no appreciable improvement in the clinical, histologic, and bacteriologic status of these patients.

Adolescent↗