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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↗
PubMed1993

Treatment of paucibacillary leprosy.

BACKGROUND: When multidrug therapy was introduced a decade ago to shorten the duration of treatment, paucibacillary leprosy was advocated 6 months of treatment. The diagnosis is based mainly on clinical and histopathologic examination, negative slit-skin smear examination, and positive lepromin test. METHODS: The case records of 508 paucibacillary leprosy patients attending our urban leprosy center have been analyzed with reference to regularity of therapy, response to multidrug regimen, follow-up, and relapse. RESULTS: The incidence of paucibacillary leprosy was found to be 37%. Defaulter rate was 45%. Nine percent of the cases attended the center with deformities emphasizing the need for corrective surgery and early case detection to prevent them. CONCLUSIONS: The main problem that we faced was the optimum duration of treatment, which is as yet an unsettled question. The opinions of other workers have been given, and a slight modification in current WHO regimen has been suggested without significantly affecting the cost of therapy.

Drug Therapy, Combination↗
PubMed1999

Infectious keratitis in leprosy.

AIM: To describe leprosy characteristics, ocular features, and type of organisms that produce infective corneal ulcers in leprosy patients. METHOD: The records of all leprosy patients admitted for treatment of corneal ulcers between 1992 and 1997 were reviewed. RESULTS: 63 leprosy patients, 53 males and 10 females, are described. 16 were tuberculoid and 47 lepromatous. 25 patients had completed multidrug therapy. 10 patients had face patches, eight had type I reaction, and 10 had type II reaction. 43 (68%) patients had hand deformities. In 54% of patients pain was absent as a presenting symptom. 19 patients gave a history of trauma. In 15 patients ulcers had also occurred on the other eye, five of them having occurred during the study period and the rest before 1992. Of the 68 eyes with corneal ulcers, 28 had madarosis, 34 had lagophthalmos, nine had ectropion, three had trichiasis, six had blocked nasolacrimal ducts, and 39 decreased corneal sensation. In 14 eyes, a previous lagophthalmos surgery had been done. 16 patients were blind at presentation. 32% of ulcers were located centrally. After treatment only 18% of the eyes showed visual improvement. Five types of fungus were cultured, two of them rare ocular pathogens. CONCLUSIONS: Corneal ulcers occur more in males and in the lepromatous group of patients. Decreased corneal sensation, lagophthalmos and hand deformity are closely associated. Indigenous treatment and late presentations were notable in many patients. Visual outcome is not good. There is increased risk of developing an ulcer in the other eye. Fungal corneal ulcers are not uncommon.

Adult↗
PubMed2004

"Tap sign" in tuberculoid and borderline tuberculoid leprosy.

Deep pain upon percussion of lesions over bone in tuberculoid leprosy, in spite of superficial sensory impairment, has been described as the "Tap Sign" (TS). This study was conducted to identify possible causes for this phenomenon and to determine the sensitivity and specificity of this sign in leprosy patients with lesions overlying bone. In 37/53 patients with lesions over bone, the sensitivity of the TS was 66.7% and the specificity was 100%. The positive predictive value was 100%, and the negative predictive value was 75%. The Tap Sign appears to be a useful clinical sign in diagnosis of tuberculoid and borderline tuberculoid leprosy where a lesion overlies a bone (sensitivity 66.7%). This test could be very useful to increase the clinical diagnostic yield, in the global perspective, in places where leprosy is diagnosed and treated by healthcare workers and primary care physicians without other laboratory facilities. Possible mechanisms responsible for the deep pain are discussed.

Adolescent↗
PubMed2001

A role for IL-12 receptor expression and signal transduction in host defense in leprosy.

The generation of cell-mediated immunity against intracellular infection involves the production of IL-12, a critical cytokine required for the development of Th1 responses. The biologic activities of IL-12 are mediated through a specific, high affinity IL-12R composed of an IL-12Rbeta1/IL-12Rbeta2 heterodimer, with the IL-12Rbeta2 chain involved in signaling via Stat4. We investigated IL-12R expression and function in human infectious disease, using the clinical/immunologic spectrum of leprosy as a model. T cells from tuberculoid patients, the resistant form of leprosy, are responsive to IL-12; however, T cells from lepromatous patients, the susceptible form of leprosy, do not respond to IL-12. We found that the IL-12Rbeta2 was more highly expressed in tuberculoid lesions compared with lepromatous lesions. In contrast, IL-12Rbeta1 expression was similar in both tuberculoid and lepromatous lesions. The expression of IL-12Rbeta2 on T cells was up-regulated by Mycobacterium leprae in tuberculoid but not in lepromatous patients. Furthermore, IL-12 induced Stat4 phosphorylation and DNA binding in M. leprae-activated T cells from tuberculoid but not from lepromatous patients. Interestingly, IL-12Rbeta2 in lepromatous patients could be up-regulated by stimulation with M. tuberculosis. These data suggest that Th response to M. leprae determines IL-12Rbeta2 expression and function in host defense in leprosy.

Antigens, Bacterial↗
PubMed1999

A recurrent case of BT leprosy with widely spread skin lesions showing a histopathology of indeterminate group after 4.5-years irregular treatment, Bangladesh.

A 29 year-old Bengali male case is presented in this paper which was a borderline tuberculoid leprosy (BT) at detection. His father contracted a lepromatous leprosy of G = 2 deformity. He took anti-leprosy drugs including MDT/MB regimen irregularly and had maculae widely-spread with anesthesia 16 months after being released from treatment (RFT). The histopathology of the maculae unexpectedly showed that of an indeterminate group of leprosy. The recurrent skin lesions were susceptive to a four-week regimen of Rifampicin and Ofloxacin. This case can not be defined as a relapsed case, because slit skin smears were always negative. It would be called a recurrent case after MDT/MB regimen. Though the reason recurrent skin lesions occur is unknown, it is reasonable to assume that the recurrent lesions are caused by dormant persisters which are originally drug sensitive. The recurrent skin lesions can not be classified because the clinical features can not be matched to their histology. Such recurrent cases might occur among the defaulters of MDT in future.

Adult↗
PubMed1991

Localized borderline lepromatous leprosy.

A 48-year-old soldier presented with 3 small leprosy lesions localized over the flexor area of the forearm. There was no nerve thickening and clinically the lesions looked like borderline-tuberculoid leprosy. However, these lesions demonstrated a bacteriological index (BI) of 4+ while no acid-fast bacilli (AFB) could be demonstrated from any other site of the body. A lepromin test was negative. Histologically evidence of borderline lepromatous leprosy was conspicuous. The case was diagnosed as localized borderline lepromatous-leprosy and treated with multidrug therapy. After 1 year of treatment, the lesions regressed, a lepromin test was positive (5 mm) and the BI from the lesions fell to 1+.

Forearm↗
PubMed1994

Integrating leprosy control into primary health care: the experience in Ghana.

Integration of leprosy control into primary health care is the most comprehensive and permanent system of delivering care to leprosy patients. But so far only a few countries have adopted this approach, largely on account of a fear of failure. Over the past decade Ghana has developed a model approach towards the transition from a vertical to an integrated programme. The highlights of our approach included the development of the leprosy service as part of the overall development of the health service, increasing capacity building for leprosy control at the district and subdistrict levels as well as the establishment of a regular and effective monitoring to identify and correct operational problems early. This paper describes the principles behind the integration, the strategies adopted and how they were implemented. It also includes the achievements made as well as the problems that were encountered and how they were solved.

Ghana↗
PubMedDate not supplied

Progression of acral bone resorption in multibacillary leprosy.

Although leprosy became a curable disease after implementation of the Global Strategy for the Elimination of Leprosy (WHO), mutilations and deformities are still commonplace in endemic countries. Hence, it remains important to evaluate the prevalence rate and the risk factors of acral bone resorption in the multidrug therapy (MDT) era. A cohort of 105 newly-diagnosed adult multibacillary leprosy patients admitted for treatment between 1990-1992 was surveyed until 1999. Progression of bone resorption (BR) in cured leprosy patients was observed up to 8 years after release from MDT. Twenty three percent of the patients were found to have acral resorption. BR was found to be associated with male sex, grade of disability at diagnosis with other deformities and with the occurrence of four or more lepra reactions. Patient surveillance after release from MDT continues to be a necessary procedure in individuals with disabilities and recurrent or persistent reactions.

Adolescent↗
PubMed1979

Defective blood mononuclear phagocyte function in patients with leprosy.

Patients with lepromatous leprosy possess a defective lymphocyte function in vivo and in vitro that is less evident in the tuberculoid form. Data concerning their macrophage ability to digest Mycobacterium leprae are controversial. The purpose of this study was to determine whether monocytes from patients with either tuberculoid or lepromatous leprosy were altered in their enzyme systems, that is myeloperoxidase-dependent and myeloperoxidase-independent systems. The ability of adherent blood monocytes to ingest and kill Candida pseudotropicalis after 30 and 60 min of incubation with yeast cells was tested. Mononuclear phagocytic cells from patients with either principal form of leprosy functioned similarly to normal monocytes in phagocytosis while their fungicidal activity for C. pseudotropicalis was statistically significantly altered and was more evident in the lepromatous than in the tuberculoid type. The results indicate that peripheral blood monocytes from patients with leprosy possess an impaired enzymatic candidacidal activity.

Adult↗
PubMed2004

[The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy].

The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy. Tuberculoid leprosy patients locally produce Th1 cytokines, while lepromatous patients produce Th2 cytokines. Signaling lymphocytic activation molecule (SLAM) and the SLAM-associated protein (SAP) participate in the differentiation process that leads to the production of specific patterns of cytokines by activated T cells. To investigate the SLAM/SAP pathway in M. leprae infection, we determined the expression of SAP, IFN-gamma and SLAM RNA messenger in leprosy patients. We found a direct correlation of SLAM expression with IFN-gamma expression, whereas the expression of SAP was inversely correlated with the expression of both SLAM and IFN-gamma. Therefore, our data indicate that SAP might interfere with Th1 cytokine responses while SLAM expression may contribute to Th1 responses in leprosy. This study further suggests that the SLAM/SAP pathway might be a focal point for therapeutic modulation of T cell cytokine responses in diseases characterized by dysfunctional Th2 responses.

Antigens, CD↗
PubMedDate not supplied

The effect of tetanus toxoid in leprosy patients.

Since cases of lepra reaction following smallpox vaccination and BCG vaccination had been reported the effect of tetanus immunisation on leprosy patients (whether it may provoke a lepra reaction or not) was studied. Three doses of purified tetanus toxoid (one ml initially, one ml after six weeks and one ml after six months) were given to 357 leprosy patients and 60 patients living in the same environ were followed as controls. The antibody response following immunisation was followed in six lepromatous leprosy patients using toxin antitoxin neutralisation test at the Lf/1000 level in mice and in three of them the antibody titre of leprosy patients rose to satisfactory level. The number of lepra reactions in these patients was monitored for nine months (two months before vaccination, during the six months period of vaccination and one month after the last dose of vaccine). There was no significant rise in the number of patients with reaction following the vaccination.

Antibodies, Bacterial↗
PubMed1991

Experimental borderline lepromatous leprosy with intraneural erythema nodosum leprosum in a mangabey monkey (Cercocebus atys).

A sooty mangabey monkey (Cercocebus atys) was inoculated with Mycobacterium leprae and developed borderline lepromatous leprosy and intraneural erythema nodosum leprosum. Previously studied mangabeys have developed only disseminated lepromatous leprosy without reactions. This case broadens the spectrum of leprosy seen in experimentally inoculated animals and further characterizes the nonhuman primate model of leprosy.

Animals↗
PubMedDate not supplied

T lymphocyte subpopulations in leprosy patients and their relation with circulating immune complexes.

The possible relationship between circulating immune complexes (CIC) and peripheral T lymphocyte populations was studied in thirteen active multibacillary leprosy (10 lepromatous--LL--and 3 borderline lepromatous--BL--) and 19 matched controls. Theophylline-resistant T cells (The-R, a lymphocyte subpopulation displaying helper activity on B cells) and total T cells were assessed by means of the E rosette technique, with and without previous theophylline incubation, 1h 37 degrees C, respectively. CIC were quantified by 125I-C1q binding test. Although leprosy patients showed a statistical non significant light depression in total T cells the remarkable variability in circulating levels of The-R T cells enabled us to separate them into two well delineated groups (in relation to this variable p less than 0.001) with no difference in age, sex and bacteriologic state: a) leprosy patients with The-R T cells proportionally conserved (6LL and 2BL); b) leprosy patients with The-R T cells proportionally depressed (4LL and 1BL). Patients belonging to the latter group showed the highest statistically significant levels of CIC. Even though we do not discard an unknown factor being responsible for our findings, we believe that this inverse relationship between elevated CIC and depressed The-R circulating T cells might be representing a lower helper activity on antibody synthesis intending to reduce its excessive production.

Antigen-Antibody Complex↗
PubMed1989

Comparison of the characteristics of infiltrates in skin and nerve granulomas of leprosy.

The characteristics of infiltrates in the dermal and neural granulomas from the same leprosy patients were compared by preparing a single cell suspension. Skin and nerve biopsies from 10 patients, 5 with tuberculoid and 5 with lepromatous leprosy were analysed. The granulomas contained lymphocytes and macrophages. Lymphocytes were the predominant infiltrating cells in the tuberculoid dermal and neural granulomas. A high proportion of lymphocytes in both the skin and nerve granulomas in these cases were activated T cells as they formed rosettes with sheep erythrocytes and expressed HLA-DR antigens. In contrast, lepromatous dermal and neural granulomas contained very few of these lymphocytes. Dermal and neural granulomas from both the types of leprosy contained mature macrophages as they were esterase positive, did not exhibit peroxidase activity and expressed HLA-DR antigens. These macrophages did not possess C3 surface receptors either. These findings suggest that the infiltrates in the skin and nerve granulomas of a given type of leprosy have similar characteristics.

Brachial Plexus↗
PubMed1989

Serum lymphocytotoxic activity in leprosy.

Sera from 167 patients across the spectrum of leprosy and 46 endemic controls were screened for lymphocytotoxic activity (LCA). The Terasaki microdroplet lymphocytotoxicity assay was performed at 37 degrees C and 15 degrees C to test sera for LCA against a panel of lymphocytes from 50 donors which represented most known HLA-ABC antigens. Raised complement-dependent LCA at 15 degrees C was seen in leprosy patients with histories of erythema nodosum leprosum (ENL) or reversal/Type I (I) reactions. Eighty-six per cent of lepromatous (LL) patients with a history of ENL (n = 21, P less than 0.001), 83% of borderline lepromatous (BL) and 88% of borderline tuberculoid patients (BT) with a history of Type I reactions (n = 12, P less than 0.01 and n = 24, P less than 0.001 respectively) had LCA compared to 39% of endemic controls (n = 46). LCA was attributed to IgM on the basis of reduced activity when serum was treated with both dithiothreitol or absorbed with antiserum for IgM. Removal of immune complexes and rheumatoid factor did not influence LCA. LCA-positive sera reacted similarly with allogeneic lymphocytes from either healthy donors or leprosy patients. Moreover LCA-positive sera reacted with autologous lymphocytes. Specificities for HLA-ABC antigens were not identified. The potential role of these autoantibodies, manifested in leprosy patients with hypersensitivity reactions remains speculative.

Adolescent↗
PubMedDate not supplied

Evaluation of circulating immune complexes in leprosy.

Circulating immune complexes (CIC) were evaluated in leprosy by 4 methods: the 125I-C1q binding assay (C1q), the platelet aggregation test (PAT), the 3.5% polyethylene glycol (PEG) precipitation test and the 2.5% PEG precipitation assay. Serum samples belonged to lepromatous leprosy bacilloscopy positive (LL+), lepromatous leprosy bacilloscopy negative (LL-), tuberculoid (TT) and first grade contact group (Co). Studies performed by the 3 first methods showed higher CIC levels in LL+ group (p less than 0.01) and lower values in the 3 others, all of them when compared to normals. On the contrary, the 2.5% PEG precipitation test gave less discriminative results giving only p less than 0.01 in LL+. CIC values obtained in the contact group showed significant results compared to normals but similar to LL- and TT groups. The C1q binding assay and the PAT were the most discriminative methods giving r = 0.90; C1q versus 3.5% PEG, r = 0.36; C1q vs 2.5% PEG, r = 0.14. The PAT compared to 3.5% PEG, r = 0.48 and PAT vs. 2.5% PEG, r = 0.24. Therefore it may be concluded as follows: a) The radioiodinated C1q binding assay and the PAT are recommended for the study of CIC in leprosy; b) The 2.5% PEG precipitation assay offers less sensitivity since it gave similar value in LL-, TT, Co and controls; c) CIC levels observed in LL+ patients may be induced by the antigenic overload demonstrated by the positive bacilloscopy; d) The contacts have CIC levels significantly different from the normal population possibly caused by a subclinical infection.

Antigen-Antibody Complex↗
PubMed1995

Elimination of leprosy as a public health problem: progress and prospects.

Leprosy is still an important problem in about 80 countries of Asia, Africa and Latin America, some 2.4 million persons being estimated to have the disease in 1994. The WHO-recommended standard multidrug therapy (MDT) was introduced in the 1980s and has been shown to be effective in combating the disease. Experiences based on many thousands of patients treated with MDT over the past decade indicate extremely low relapse rates (cumulative relapse rates around 1%). By the end of 1993, some 5.6 million patients had been cured, and the global cumulative MDT coverage of registered patients had reached 89%. The number of registered cases fell from 5.4 million in 1985 to 1.7 million in 1994. The significant progress made in leprosy control enabled the World Health Assembly in 1991 to set a goal for eliminating leprosy as a public health problem by the year 2000. One important epidemiological factor is that leprosy is very unevenly distributed: 80% of the problem is confined to only five countries and 92% to just 25 countries. The elimination strategy envisages identifying and treating with MDT a total of about 5 million cases from 1994 to the year 2000. The cost of dealing with these cases has been estimated at US$ 420 million, including US$ 150 million for the drugs.

Africa↗