[2 cases of familial leprosy: tuberculoid leprosy of the father and lepromatous leprosy of the son].
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Cytokines in leprosy, II. Effect of treatment on serum cytokines in leprosy.
BACKGROUND: Multidrug therapy (MDT) causes a decrease in the bacterial burden in leprosy patients. Does the decrease in the antigenic stimulation of the immune system have an effect on cytokine production? METHODS: The effect of treatment on serum cytokines was evaluated in 36 leprosy patients and 35 reactional leprosy patients and compared with that in 20 age- and sex-matched healthy individuals. The enzyme-linked immunosorbent assay (ELISA) technique was used to measure serum levels of interleukin-2 receptor (IL-2R), interleukin-10 (IL-10), and interleukin-1beta (IL-1beta) before and after treatment. These cytokines represent T-helper 1 (TH1), T-helper 2 (TH2), and macrophage cytokines, respectively. RESULTS: The studied serum cytokines were significantly reduced after 1 year of treatment in leprosy patients. The degrees of reduction were significantly positively correlated with a reduction in the bacterial index (BI) and morphologic index (MI). After 1 year of MDT (but not 6 months), paucibacillary (PB) patients showed a significant reduction in all the studied serum cytokines to levels comparable with those of healthy controls. Multibacillary (MB) patients also showed a significant reduction in all the studied serum cytokines, but the levels were still significantly higher than those of healthy controls. Leprosy patients with high levels of serum IL-1beta were more susceptible to the development of reactions after the initiation of treatment. Corticosteroid therapy of reactional patients resulted in a significant reduction in the studied serum cytokines to levels similar or lower than those of nonreactional leprosy patients. The dose of steroids showed a significant positive correlation with the amount of decrease in IL-1beta. CONCLUSIONS: MDT caused a reduction in serum cytokines correlated with a reduction in the bacterial burden. It is advisable to continue MDT for PB patients for 1 year. Serum IL-1beta levels may have a prognostic value for the susceptibility of leprosy patients to the development of reactions.
Adrenal Cortex Hormones↗
Antibodies to sulfatide in leprosy and leprosy reactions.
Antibodies to sulfatide have been reported in various demyelinating peripheral polyneuropathies. We have investigated the diagnostic value of these antibodies in leprosy. Anti-sulfatide IgM in leprosy patients was not significantly elevated. High anti-sulfatide IgG titers were observed in individuals from endemic areas, irrespective of their leprosy status, while western European controls were negative. No significant correlation was found between IgM or IgG antibody titers and leprosy classification, although multibacillary patients had higher anti-sulfatide IgM titers than paucibacillary patients. In addition, 23 patients developing leprosy reactions were followed longitudinally. Antibody titers in these patients fluctuated slightly during the follow-up period. There was no association with the occurrence of leprosy reactions or treatment. Thus, IgG titers against sulfatides are high in both leprosy patients and healthy controls in endemic areas, whereas such antibodies are not found in western European controls, suggesting that these antibodies are induced by environmental factors, such as microorganisms.
Antibodies↗
Chemoprophylaxis is effective in the prevention of leprosy in endemic countries: a systematic review and meta-analysis. MILEP2 Study Group. Mucosal Immunology of Leprosy.
OBJECTIVE: To quantify the efficacy of chemoprophylaxis against leprosy. METHOD: Literature searching of Medline and Embase databases, hand-searching of references and correspondence with investigators. STUDY SELECTION: published papers relating to the prevention of leprosy and the use of chemotherapy in leprosy were identified for critical appraisal. Trials were selected and grouped into three categories according to study design and control groups. DATA ANALYSIS: the relative risks (RR) with 95% confidence intervals were calculated from the original data using a random effects model. To assess the cost-effectiveness of chemoprophylaxis, a further analysis of the rates of disease in the trial and control groups was done based on the numbers needed to be treated (NNT) to prevent one new case of leprosy. RESULTS: A total of 14 trials were identified from 127 published papers on chemoprophylaxis of leprosy. The trials were categorized into randomized controlled trials, non-randomized controlled trials, and uncontrolled trials. The overall results of the meta-analysis shows that chemoprophylaxis gives around 60% protection against leprosy. The NNT are low in trials of household contacts. CONCLUSIONS: The evidence shows that chemoprophylaxis against leprosy is an effective way to reduce the incidence of leprosy, particularly in household contacts. The role of chemoprophylaxis needs to be re-examined using newer drugs given the continuing case detection rates globally.
Acedapsone↗
Design of the leprosy component of the Brazilian BCG revaccination trial for assessing BCG effectiveness against leprosy in school children.
BACKGROUND: BCG vaccination confers protection against leprosy, and vaccination among household contacts has been recommended in Brazil. Nevertheless, vaccination of the entire community against leprosy is not advocated as leprosy has low incidence in most populations. Despite that, in Brazil, BCG vaccination is recommended among school children to prevent tuberculosis and this large scale vaccination may also affect the occurrence of leprosy, which led to investigations of its impact on leprosy in endemic areas of Brazil. OBJECTIVES: To estimate the effectiveness against leprosy of a dose of BCG vaccine given to school children in a population with a high coverage of neonatal BCG. Long term objectives are to compare the impact of vaccination among schoolchildren with the existing recommendation to vaccinate household contacts of leprosy. STUDY DESIGN: Cluster randomized controlled field trial with no placebo. STUDY POPULATION: Children aged 7 to 14 years attending state schools with high coverage of neonatal BCG. METHODS: 286 state schools in the city of Manaus, Brazil, were randomized to receive BCG or not. Identifying information was collected for 152,438 school children, of whom 72,980 are in intervention schools. BCG vaccination was given intradermically to children in schools allocated to vaccination. Follow-up relies on ascertainement of cases diagnosed at the health services and notified to the reference center for leprosy.
Adolescent↗
Interferon-gamma responses to candidate leprosy skin-test reagents detect exposure to leprosy in an endemic population.
New tools for the detection of leprosy exposure in a community will be necessary for the eradication of leprosy. Candidate leprosy skin-test antigens derived from the fractionation of the leprosy bacillus into cytoplasmic and cell-wall proteins free of immuno-inhibitory mycobacterial lipoglycans and carbohydrates were used in an overnight blood test to determine whether exposure to leprosy can be detected by the production of the cytokine interferon gamma (IFN-gamma). Strong IFN-gamma responses were detected in leprosy contacts to both skin-test antigens compared with control subjects from the same endemic communities. There was little response in patients with tuberculosis. Responses were greatest in contacts with recent leprosy exposure. The implications of these findings for the application of these reagents in a field trial as skin tests to detect exposure to leprosy are discussed in light of the strong association between overnight IFN-gamma to PPD and the tuberculin skin-test responses previously reported.
Adolescent↗
Biochemical, immunological and genetic studies in leprosy. II. Profile of immunoglobulins, complement components and C-reactive protein in sera of leprosy patients and healthy controls.
Various classes of immunoglobulins (IgA, IgM, IgG, IgD and IgE), complement components (C3 and C4) and C-reactive protein (CRP) were estimated in sera from normal healthy controls and leprosy (lepromatous and tuberculoid) patients from Ethiopia. Higher levels of IgA, IgM, IgG and IgD were found in lepromatous leprosy compared with normal healthy people while in tuberculoid leprosy only IgM, IgG and IgD levels were increased. Borderline leprosy patients showed increase in IgG level only. Although an increase in IgE was noted in lepromatous leprosy, it was not significant; the variations in IgE levels could be due to different socioeconomic background and exposure to intestinal parasites. C3 component was significantly reduced in leprosy patients compared with healthy controls while no difference in C4 component was observed. The results point towards an involvement of the "alternate pathway". A positive test against C-reactive protein antiserum was given by about 20% of the normal healthy controls while more than 60% lepromatous and tuberculoid leprosy patients were CRP positive. The results are discussed in relation to the status of immunoglobulins and complement components in leprosy and possible factors (environmental and genetic) which might affect them.
C-Reactive Protein↗
Dehabilitation of leprosy-affected people--a study on leprosy-affected beggars.
Leprosy is one of the most socially stigmatized diseases known today. Social stigma is associated mainly due to the prevalent myths like its hereditary and contagious nature, divine curse along with the physical deformities caused. The affected people not only face physical impairments but also suffer psychosocial repercussions due to the community's attitude. The long-term physical and psychosocial restrictions slowly push the leprosy-affected person out of the society. With lack of social support and self-confidence, some dehabilitated leprosy-affected persons end up as beggars. The present study focuses on the long-term consequences of leprosy. It is based on case studies of leprosy-affected beggars in Delhi. The process of dehabilitation in each case has been studied. It has been found that dehabilitation is a continuous process. The combination of leprosy, physical impairments and social stigma causing further participation restriction, lead to dehabilitation of people affected by leprosy, and ending in a state of beggary for some. There is a need to develop a holistic approach including both prevention of dehabilitation and rehabilitation of those dehabilitated to overcome both the disease and its consequences. Measures to prevent such dehabilitation in future along with the rehabilitation of leprosy-affected beggars have been suggested. Both these measures should take place simultaneously.
Adult↗
An analysis of the pattern of detection of leprosy patients by institutions in the general health services in Sri Lanka after the integration of leprosy services into general health services.
Integration of leprosy services into the General Health Services was initiated in 2001 in Sri Lanka, and by the end of 2003 all services related to leprosy care were fully integrated. Against this background, routinely collected data available at the Anti-Leprosy Campaign for a 3-year period from 2000-2003 were analyzed to identify the pattern of the detection of cases by hierarchical institutions in the General Health Services. The analysis showed that more than 75% of leprosy patients had been detected at base, general and teaching hospitals and this trend was increasing proportionally during the period of concern (P < 0.001). Teaching hospitals had detected more than 50% of patients and this trend was also proportionally increasing. Nearly one-third of patients detected at teaching hospitals had been detected at the Central Leprosy Clinic (CLC) at the National Hospital. The trend for case detection at the CLC was decreasing proportionally and in absolute terms during the 3-year period after integration. More than 60% of leprosy patients had been detected at institutions where consultant dermatologists were available. The analysis concluded that centralized leprosy diagnostic and treatment services have been taken over by the institutions in the General Health Services but within districts these activities are predominantly concentrated on higher level institutions with consultant dermatological services. This suggests that similar to the existing general trend of by passing of lower level institutions by patients to seek treatment at higher-level institutions, which are perceived to provide a service of better quality, leprosy patients too prefer to seek treatment at these institutions.
Consultants↗
Indeterminate leprosy: histopathologic and histochemical predictive parameters involved in its possible change to paucibacillary or multibacillary leprosy.
In an attempt to find clinical, bacteriological, histopathological, and immunohistochemical parameters to predict the progress of indeterminate leprosy patients to either paucibacillary (PB) or multibacillary (MB) leprosy, skin biopsies from 51 patients with indeterminate leprosy were retrieved from the files of the São Paulo Health Institute (Brazil). All of these patients had progressed to either PB or MB leprosy over a period of time which varied from 2 months to 24 years. Clinical records were examined, and new sections were cut from the paraffin blocks and stained by hematoxylin-eosin and Fite-Faraco stains; the avidin-biotin peroxidase technique was used with primary antibodies to detect bacillary antigens (anti-BCG serum) and nerve branches (anti-S-100 protein anti-serum). A moderate (++) or strongly positive ( ) Mitsuda skin test was observed in some patients progressing to PB leprosy. Noteworthy is that even patients initially Mitsuda negative may evolve to PB leprosy. a) A 2+ bacterial index and/or the presence of bacilli, even though few in number, in various dermal structures; b) multiple positive antigen sites as detected by anti-BCG anti-serum; and c) dermal nerve involvement, when evaluated as single parameters, correlated with a progression indeterminate to MB leprosy. An index resulting from the summation of the above three parameters identified 13 (72%) of 18 of these cases which progressed to MB leprosy.
Adolescent↗
Leprosy control activities of the International Federation of Anti-leprosy Associations.
The International Federation of Anti-leprosy Associations (ILEP) founded in 1966, consists of 22 autonomous nongovernmental organizations raising funds from the general public in the North for anti-leprosy work in the South. ILEP Member associations support over 800 field projects in 92 countries, in addition to over 130 research and other projects with a total annual expenditure of about US+ 60 million. 72% of the resources are spent on leprosy-control activities, 12% on training, 10% on research and 6% on socioeconomic activities. About 55% of resources are devoted to activities of national/regional leprosy programmes. ILEP-supported projects had detected over 100,000 patients in 1988. ILEP Member associations introduced WHO-recommended multidrug therapy (MDT) quite early, and the coverage for MDT in ILEP-supported projects has increased from 8% in 1984 to 35% in 1988 (271,000 patients in 1989 out of 769,000 on treatment). ILEP Member associations are currently supporting approaches towards integration of leprosy control with other services, urban leprosy programmes and social and physical rehabilitation. Thanks to their flexibility, their sense of innovation and their commitment to the worldwide anti-leprosy campaign, ILEP Members are well placed to meet the challenge of making MDT available to all leprosy patients by the year 2000.
Communicable Disease Control↗
IgM serum antibodies to phenolic glycolipid-I and clinical leprosy: two years' observation in a community with hyperendemic leprosy.
A village population with hyperendemic leprosy in Papua New Guinea was repeatedly examined for clinical leprosy and for serum IgM antibodies to phenolic glycolipid-I (APGL-I) over 2 years between 1984 and 1986. In 1984, serum APGL-I was elevated in 15% of the subjects without clinical leprosy, and the prevalence of seropositivity was not significantly different in subjects from households with or without leprosy. In 1986, the prevalence of elevated serum APGL-I in leprosy-free subjects had risen to 23%. The incidence of seroconversion from APGL-I negative to APGL-I positive was 9.5% per year (95/1000 person years) in 253 subjects tested in 1984 and 1986. During the same period, 27 of 40 (67%) leprosy-free subjects reverted from positive to negative. The positive seroconversion rate in the community was higher than the incidence of clinical leprosy (11.2/1000 person years) over the same period. However, elevated serum APGL-I was not associated with clinical disease and failed to predict the development of disease over 2 years. The significance of persistent seropositivity found in 14 (5%) leprosy-free subjects is uncertain.
Adolescent↗
T-cell responses to fractionated antigens of Mycobacterium w, a candidate anti-leprosy vaccine, in leprosy patients.
Mycobacterium w, an atypical cultivable mycobacterium, is undergoing phase III clinical trials as a vaccine against leprosy in India. It has brought about lepromin conversion and histopathological upgradation in a significant number of patients studied so far. It is important to identify antigens of M. w that trigger T-cell responses in leprosy patients vaccinated with this organism. In the present study the peripheral T-cell repertoire of 12 M. w-vaccinated leprosy patients, 10 unimmunized leprosy patients, 8 tuberculoid and 5 healthy contacts was analysed with fractionated antigens of M. w. The lepromatous leprosy patients who are in general anergic to antigens of M. leprae did not respond to antigens of M. w. However, peripheral blood mononuclear cells obtained from leprosy patients who had been vaccinated with M. w responded to many antigens. These responses were frequently directed against low molecular weight entities of 14-45 kDa. T cells from tuberculoid leprosy patients and healthy contacts also responded predominantly to a number of low molecular weight antigens of M. w. The study also identified an immunodominant 28-31 kDa antigenic fraction carrying T- as well as B-cell activating determinants.
Antigens, Bacterial↗
Reduction of epidermal cell proliferation in skin lesions in lepromatous leprosy is greater than in indeterminate and tuberculoid leprosy lesions.
We have compared epidermal cell proliferation in skin biopsies from areas with lesions to contralateral areas without lesions in patients with indeterminate, tuberculoid and lepromatous leprosy. Cell proliferation was determined as the percentage of labeled cells in the basal and suprabasal epidermal layers, using autoradiographic preparations of skin biopsies taken 1 hr after a 3H-thymidine intradermal injection. We have found a significant reduction in epidermal cell proliferation in areas with lesions in the three groups of patients. The greatest reduction occurred in lepromatous patients. In lesions of patients with indeterminate or tuberculoid leprosy, the reduction was the same, and in both groups it was smaller than in lepromatous patients. In the areas without lesions, the index of labeled cells was similar to that of "normal" skin of nonleprosy patients. In the contralateral unaffected areas from leprosy patients and in "normal" skin from nonleprosy patients, as well as in affected areas from patients with indeterminate leprosy, epidermal cell labeling was greater in the suprabasal layer than in the basal layer. In lesions of lepromatous patients, cell labeling was greater in the basal layer than in the suprabasal layer. Our findings suggest that the reduction of epidermal cell proliferation in leprosy patients is restricted to the cell-mediated immune response, more intense in lepromatous leprosy. It does not seem to be related to denervation, which is greater in tuberculoid leprosy.
Adult↗
Association of the mycobacterial 30-kDa region proteins with the cutaneous infiltrates of leprosy lesions. Evidence for the involvement of the major mycobacterial secreted proteins in the local immune response of leprosy.
The granulomatous skin lesions of human leprosy are known to be due to the cutaneous immune reaction to various mycobacterial antigens. In the present study, by immunohistochemical analysis using a previously characterized monoclonal antibody (MoAb) 3A8 we have demonstrated a selective expression of the 3A8 epitope of mycobacterial 30-kDa proteins, the major secreted proteins of mycobacteria, in various forms of leprosy lesions across the clinical spectrum. The localization of MoAb 3A8 staining is confined to the areas of cellular infiltrates of the lesions. In tuberculoid lesions the intense 3A8 staining was seen mostly in association with the membrane of the dermal cellular infiltrates whereas in highly bacilliferous lepromatous lesions the staining seems to be diffused with granular appearance but not in the form of bacteria. In patients with reversal reaction the staining was specifically extended to cells infiltrating the epidermis. MoAb 3A8 did not show any reactivity with inflammatory skin lesions of patients other than those with leprosy. Since the 3A8 epitope of 30-kDa proteins has been shown to be present in all cellular compartments of the mycobacteria and in the actively secreted BCG 85 antigen complex, MoAb 3A8 reactive protein(s) in leprosy lesions may be derived either from degraded somatic mycobacterial products or from antigens actively secreted by live bacilli. The latter could be true in the cases of untreated lepromatous lesions with high bacterial load since live M. leprae has also been considered to secrete corresponding 30-kDa proteins similar to other closely related mycobacteria. By double immunoenzyme staining we clearly demonstrate the expression of 3A8 epitope on CD68+ macrophages in the granulomas of tuberculoid leprosy, whereas in highly bacilliferous lepromatous lesions most of the double staining was seen in a diffuse pattern within the interstitial space of the cellular infiltrate as well as in the cytoplasm of CD68+ macrophages. In lesions from reversal reaction the 3A8 epitope is more strongly expressed on CDla+ dendritic Langerhans cells (LC) both in the epidermis and in the dermis as compared with other types of leprosy. This provides evidence for the involvement of LC in handling of mycobacterial antigenic epitopes in leprosy lesions. Further, immunoenzyme double staining revealed that the expression of this mycobacterial 3A8 epitope on antigen presenting cells such as CD68+ macrophages and CDla+ LC is present in juxtaposition with CD3+ T cells including the alpha beta and gamma delta receptor-bearing T cells in the granuloma.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibodies, Monoclonal↗
Lymphocyte transformation test in leprosy: decreased lymphocyte reactivity to Mycobacterium leprae in lepromatous leprosy, with no evidence for a generalized impairment.
Untreated leprosy patients were examined with respect to lymphocyte transformation in vitro after stimulation with mycobacterial and other microbial antigens, allogeneic lymphocytes, or nonspecific mitogens. Methods were used to circumvent technical variability. The results were compared with those obtained in controls matched for age, sex, race, and environment. No evidence was found for a generalized impairment of lymphocyte transformation in vitro, whereas a specific defect towards Mycobacterium leprae was demonstrable in lepromatous leprosy patients. The response to M. leprae, investigated in untreated and treated leprosy patients, decreased along the leprosy spectrum. Moreover, the results of the one-way mixed lymphocyte cultures showed that lymphocytes from leprosy patients had a normal stimulator and responder capacity, when they were tested against a panel of allogeneic lymphocytes. The influence of serum factors was investigated in untreated leprosy patients in the mixed lymphocyte culture. On average, tuberculoid as well as lepromatous sera showed a low-level depressive effect, but some sera showed a stimulatory effect. Therefore, a depressive effect of serum factors cannot be considered to be a general feature of leprosy. The correlation between the Mitsuda type of lepromin skin test and the lymphocyte reactivity in vitro to M. leprae was studied, and a positive correlation was found.
Antigens, Bacterial↗
Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans.
Twin and family studies indicate that host genetic factors influence susceptibility to leprosy and, possibly, leprosy type. Murine studies have suggested a role for the natural resistance-associated macrophage protein 1 (Nramp1) gene, which can influence cellular immune responses to intracellular pathogens. We evaluated a variation in the human homolog, NRAMP1, recently associated with tuberculosis susceptibility in West Africa. A total of 273 patients with leprosy and 201 controls from Mali were genotyped for NRAMP1 polymorphisms previously associated with tuberculosis. No association was found with leprosy per se (P = 0.83), but the NRAMP1 3'-untranslated region 4-bp insertion/deletion polymorphism was associated with leprosy type (P = 0.007). Heterozygotes were more frequent among multibacillary than paucibacillary leprosy cases. Thus, variation in or near the NRAMP1 gene may exert an influence on the clinical presentation of leprosy, possibly by influencing cellular immune response type.
Adult↗
Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic area: comparison between Bangladesh and Thailand.
BACKGROUND: As part of a larger study of the role of close contacts in the transmission of M. leprae, we explored whether the proportion of newly detected cases with a family history of leprosy differs with different incidence rates of leprosy in a population. METHODS: Retrospective analysis was performed of contacts of all new leprosy patients diagnosed during a 10-yr period in well-established leprosy control programs in Thailand and Bangladesh. By our definition, a contact group consisted of the new case and of past and present cases who were relatives and in-laws of the new case. For a new case, the nearest index case was defined on the basis of time of onset of symptoms for the cases in the contact group, in combination with the level of closeness of contact between these cases and the new case. Three contact levels were distinguished. In Bangladesh these levels were defined as 'kitchen contact'; 'house contact'; and 'non-house contact'. In Thailand comparable levels were defined as 'house contact'; 'compound contact'; and 'neighbor contact'. RESULTS: In Bangladesh 1333, and in Thailand 129 new patients were included. The average new case detection rate over 10 yrs was 50 per 100,000 general population per year in Bangladesh, and 1.5 per 100,000 in Thailand. In the high endemic area 25% of newly detected cases were known to belong to a contact group and were not the index case of this group, whereas in the low endemic area 62% of newly detected cases had these characteristics. The distribution of the nearest index cases over the three contact levels was comparable in both areas. Just over half of the nearest index cases were found within the immediate family unit ('kitchen' in Bangladesh; 'house' in Thailand). CONCLUSION: The results indicate that in a low endemic area a higher proportion of newly detected leprosy cases have a family history of leprosy compared to a high endemic area. Different contact levels and their relative risks to contract leprosy need to be established more precisely. In high endemic situations the circle of contacts that should be surveyed may need to be wider than currently practiced.
Adolescent↗