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IgM antibodies to native phenolic glycolipid-I in contacts of leprosy patients in Venezuela: epidemiological observations and a prospective study of the risk of leprosy.

In a randomized, double-blind vaccine trial in Venezuela, about 29,000 contacts of leprosy patients have been vaccinated with either a mixture of heat-killed Mycobacterium leprae and BCG or BCG alone, and are being re-surveyed annually to detect new cases of leprosy. All contacts had a serum sample collected at the time of entry into the trial, and 13,020 of these sera have been analyzed for antibodies to phenolic glycolipid-I (PGL-I). Antibody levels have been related to various characteristics of the contacts and to their risk of developing leprosy in the following 4 years. A strong association was found between PGL-I antibody level and the risk of developing leprosy, in spite of possible modification of the incidence rate induced by vaccination. Antibody levels were higher in females than in males, and declined progressively with age. Household contacts had higher levels than did non-household contacts, and levels were higher in individuals from the state in Venezuela which has the highest incidence of the disease. No substantial differences were found in antibody levels between contacts of multibacillary and paucibacillary patients, which may in part reflect the influence of treatment, and there was no clear association with the presence of BCG or lepromin scars or with skin-test responses to PPD and leprosy soluble antigen. The assay of antibodies to PGL-I seems unlikely to provide a sensitive or specific test for infection with M. leprae, and measuring PGL-I antibody levels as a screening procedure to identify those at high risk of developing leprosy is unlikely to be particularly useful in most leprosy control programs. Such assays may be useful for the epidemiological monitoring of changes in the intensity of infection with M. leprae in a community and for the study of carefully defined groups of contacts during some phases of control programs.

Adolescent↗

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↗

Immunologic defects in leprosy patients. I. Evidence of immune aberration of suppressor-T lymphocytes in lepromatous leprosy.

Immunoregulation in various types of leprosy patients was evaluated in vitro using peripheral blood mononuclear leukocytes (PBML) stimulated with phytohemagglutinin-P (PHA-P) or concanavalin A (ConA) for a cell-mediated immune (CMI) assay or pokeweed mitogen (PWM) for a humoral-mediated immune (HMI) assay. The immune responses were evaluated by a lymphocyte transformation test (LTT) and lymphocyte-mediated cytotoxicity (LMC) for the immunoregulation of CMI, and a reverse hemolytic plaque assay for measuring the plaque-forming cells (PFC) and a sandwich ELISA for measuring IgG concentrations for the immunoregulation of HMI. In LTT with PHA-P or ConA, the mean of the normal controls was not significantly different from the means of the untreated LL, BL, BB, BT, and TT leprosy patients. However, a wide variation of LTT results from BT to LL patients was noted: the LTT results of TT patients and normal controls were less variable. A similar pattern of immune responses was noted when studied by LMC in untreated LL, BL, BB, BT, and TT leprosy patients and normal controls. When the untreated patients and normal controls were studied for PFC, using PBML stimulated with PWM, a very similar pattern of PFC was obtained with the different types of leprosy patients. The immunoregulatory role of lymphocytes in leprosy patients was further evaluated by cell mixing cultures. ConA-stimulated PBML from lepromatous leprosy patients were mixed with normal PBML and then stimulated with PHA-P.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity Tests, Immunologic↗

Leprosy and confinement due to leprosy show high association with hepatitis C in Southern Brazil.

Leprosy is a disease, which is accompanied by cellular immunity defects, which may increase the susceptibility of patients in developing co-infections. The association of leprosy with hepatitis C virus (HCV) infection, human immunodeficiency virus types 1 and 2 (HIV 1+2) infection and human T-lymphotropic virus types I and II (HTLV I+II) infection have previously been described in different populations. In this study, the prevalence of these infections was determined in 199 Southern Brazilian leprosy patients and in 681 matched controls. Antibodies to HCV were positive in 3.52% of the patients (7/199) and in 0.15% of the controls (1/681; odds ratio (OR)=24.79; 95% CI=3.03-202.74; p=0.0002). An increased risk of HCV infection was observed in institutionalized patients (OR=14.95; 95% CI=1.76-127.03; p=0.004) and in the lepromatous form of the disease (OR=7.67; 95% CI=0.43-136.62; p=ns). Anti-HIV 1+2 antibodies were positive in only one out-patient (1/199; 0.50%) and in none of the controls (0/681; OR=3.43; 95% CI=0.21-55.16; p>0.05). No leprosy patient was positive for anti-HTLV I+II antibodies. These results demonstrate an increased prevalence of HCV infection in leprosy patients from South Brazil and that both institutionalization and lepromatous form of the disease confer higher risk to HCV infection. These data emphasizes the importance of monitoring hepatitis C and leprosy interactions and the need of special care to institutionalized and lepromatous patients in preventing HCV co-infection.

Adolescent↗

Comparative assessment of the leprosy antibody absorption test, Mycobacterium leprae extract enzyme-linked immunosorbent assay, and gelatin particle agglutination test for serodiagnosis of lepromatous leprosy.

A comparative assessment of three serological methods for leprosy diagnosis (the fluorescent leprosy antibody absorption [FLA-ABS] test, the Mycobacterium leprae soluble-extract enzyme-linked immunosorbent assay [ELISA], and the M. leprae particle agglutination [MLPA] test) was carried out. The objective was to identify their performance in clinical and epidemiological diagnosis of leprosy. The study group included 45 lepromatous leprosy patients under treatment. Specificity was > 95% for all three assays, and sensitivity was 95, 58, and 74% for the FLA-ABS test, the MLPA test, and the ELISA, respectively. The only cross-reactivity for M. tuberculosis-infected patients was with the soluble-extract ELISA. Although the FLA-ABS test displayed the highest specificity and sensitivity values, it can only be used in well-developed laboratories, and the patient's clinical and epidemiological background must be considered when results are interpreted because the test remains positive after therapeutic success and could be positive for some household contacts. The MLPA test is easier to perform and interpret, and it is adequate for small laboratories and epidemiological studies intended to detect active untreated or irregularly treated leprosy cases. Therefore, the FLA-ABS and MLPA tests are complementary, and both should be used for serodiagnosis of leprosy.

Agglutination Tests↗

Progress towards elimination of leprosy as a public health problem in India and role of modified leprosy elimination campaign.

India (population 943 million) has seen a highly significant decrease in the prevalence of leprosy since the introduction of multi-drug therapy (MDT) in 1981. From a prevalence rate of 57/10,000 of the population in March 1981, the figure has declined to 5.2/10,000 in March 1999. This was possible due to the creation of a completely vertical (specialized) infrastructure for leprosy control in the 218 endemic districts of the country and skeleton vertical staff in the remaining districts, coupled with the recruitment of additional staff on contract basis to provide MDT through vertical staff in endemic districts and mobile treatment units in the moderate and low endemic districts. Despite all efforts, however, new case detection has not shown a decline over the last 14 years due to the presence of hidden (and undiagnosed) cases. Therefore, in order to intensify and hasten progress towards elimination (less than 1 case per 10,000 of the population) in the whole country, it was decided to implement a massive leprosy elimination campaign (LEC) in all the States/Union Territories (UTs). The reports of 22 States/UTs indicate that 415 out of the total of 490 districts in the country were covered by modified LEC (MLEC), with 85% coverage of the population. The campaign used in India was modified from the pattern previously described by the World Health Organization. The detection of hidden or suspected cases took place within a short, intensive period of 6-7 days and relied heavily on house-to-house searches by General Health Care staff trained in leprosy detection and confirmation was made by appropriately trained staff. This MLEC received widespread Government and public support, resulting in the detection of 454,290 hidden cases of leprosy, whilst providing training to a large number of General Health Care staff and volunteers and creating widespread awareness about leprosy and the availability of treatment free of charge for all cases. This programme proved to be one of the most successful health care interventions undertaken in India in recent years, particularly in the states of Bihar and Orissa. Although a few states in India are unlikely to reach the current WHO goal of elimination before end of the year 2000, the results of the MLEC strongly support the possibility that elimination levels will be achieved in the majority of states by the end of the year 2000 and at national level by the end of the year 2002.

Health Promotion↗

Leprosy: between acceptance and segregation. Community behaviour towards persons affected by leprosy in eastern Nepal.

This study describes community behaviour towards persons affected by leprosy in the eastern Terai districts of Nepal. The results show that 95% of the persons affected by leprosy recognized by the community have visible signs such as wounds, swellings and deformed feet or hands. Persons affected by leprosy still experience negative behaviour. Motives for negative community behaviour are mostly found in the fact that people fear infection by germs, but fear of a curse from God is also mentioned. This study shows that negative community behaviour is still present in eastern Nepal. Leprosy is more than a disease; the disease can nowadays be medically cured, but the sickness of leprosy still remains. Leprosy control programmes should focus on prevention of impairments and disabilities, because it seems that a visible sign is an important trigger for negative community behaviour.

Adult↗

Leprosy XII. Quantitative analysis of thymus-derived lymphocyte response to phytohemagglutinin in leprosy.

The immune status of various leprosy patients was evaluated by using a micromethod to evaluate lymphocyte responses to phytohemagglutinin (PHA). In our study, whole blood was used and the degree of response to PHA stimulation was expressed in terms of unit volume of blood. A markedly decreased response to PHA stimulation was noted in patients with active lepromatous leprosy. Patients with active lepromatous leprosy who have been proved drug (DDS) resistant showed less response than did those of drug sensitive patients with active lepromatous disease, while the patients with active lepromatous leprosy complicated by erythema nodosum leprosum (ENL) showed higher response than did those of patients with no complicated ENL. Comparing the results obtained to those obtained using other methods for T cell analysis indicates that these results reflect the number of T lymphocytes in the leprosy patient. Thus, this simple method is of value in assaying the presence and responses of T lymphocytes in the leprosy patient.

Dapsone↗

Prevalence of leprosy among household contacts of leprosy cases in western Orissa.

The prevalence rate of leprosy among household contacts is an important epidemiological indicator in the character and trend of the disease. During the period January 2001 to December 2002, families of 400 primary cases were studied to detect contact (secondary) cases. Seventy-two cases were detected from 54 families; of these 72 cases, 45 (62.5%) were in the paediatric age-group (0-14 years) and of these 45.8% belonged to 6-14 years group. Out of the 72 cases, there were more (58) of paucibacillary (PNL+I+TT+BT) cases. Secondary cases were significantly high when there was lepromatous type of leprosy in the family. The attack rate among those exposed to paucibacillary type (TT, BT) of leprosy, though much less, was still observed. The influence of duration of contact revealed that a maximum number of cases (N=43, 59.7%) acquired the disease during 0-6 years of contact. A majority of the patients belonged to low-income groups, were illiterate and lived in extended families. The father was the source case for most of the secondary cases (N=41, 57%). Conjugal leprosy was very rare. The results of the study points to the fact that PB leprosy is still a potential source of infection and cannot be ignored. It is important to evolve a hospital-based surveillance programme for contacts of leprosy patients since early detection and treatment of contacts are important measures for reducing the reservoir of infection in the community.

Adolescent↗

Assessment of knowledge and skills in early diagnosis of leprosy and attitudes towards leprosy amongst doctors working in dermatological services, Shandong Province, People's Republic of China.

After the leprosy control programme in Shandong Province, China, had declared elimination in 1994, it was no longer cost effective to rely on rapid surveys, population surveys and contact tracing for case detection, and since then most new cases have been diagnosed by the dermatological services. The dermatological services will continue to play an important role in diagnosis of the few incident leprosy cases scattered in wide geographic areas and in a population of 90 million. In order to better understand the knowledge and skills in early diagnosis of leprosy among doctors working in dermatological services around the province, doctors attending the dermatological annual meeting and a dermatological training workshop were assessed on their knowledge and skills in early diagnosis of leprosy and their attitude towards leprosy with a semi-structured questionnaire. The results showed that continuous training was needed for dermatologists from both general hospitals and the leprosy control programme. In particular, the training methods for the skills in nerve examination including palpation of peripheral nerves and nerve function assessment should be improved.

Adult↗

Evaluation of fluorescent leprosy antibody absorption test versus enzyme-linked immunosorbent assay with phenolic glycolipid 1 and their use in immuno-epidemiological studies on leprosy.

We systematically conducted comparative studies on the validity, reliability and practicality of FLA-ABS.T/PGI-ELISA in large samples. Namely, 284 leprosy patients, 20 tuberculosis patients, 172 normal controls (from nonendemic area of leprosy), 425 leprosy household contacts (HC) and 2573 random samples from the general population (RS) were involved. The results indicated that FLA-ABS.T/PGI-ELISA are highly sensitive and specific for detecting antibodies against M. leprae. Their Youden's indexes (YI) are greater than 90%, and the positive predicative and negative values are 90%. The test results agreed with immuno-epidemiological studies: 1. The positive rates using FLA-ABS.T/PGI-ELISA increased gradually from TT to LL leprosy patients (in HC, the positive rates of PGI-ELISA were much higher in contacts of multibacillary patients than in contacts of paucibacillary patients); 2. The positive rates detected by FLA-ABS.T were identical to those of PGI-ELISA both in HC and in RS; 3. Among RS, the positive rates detected by FLA-ABS. T/PGI-ELISA were similar in each district and were in concordance with the general prevalence rates. Thus, both FLA-ABS.T and PGI-ELISA are useful tests in diagnosing leprosy and detecting subclinical infection with M. leprae. However, because the PGI-ELISA is simple, it will be more practical than FLA-ABS.T in the future. The authors emphasize that the methodology of obtaining dried blood from ear lobes is important for the immuno-epidemiological study of leprosy on a large scale.

Antigens, Bacterial↗

Prevalence of leprosy in slums in Bombay including a leprosy colony.

Transmission of leprosy which is related directly to the total quantum of infection in the community as a whole is decided by the existence of patients suffering from progressive and infectious forms of leprosy and their movement from place to place. This information is of great importance in cities like Bombay to identify the priority areas as targets towards which control efforts should be directed. In this presentation an attempt has been made to compare the leprosy survey figures from three different situations in the city. Selection is arbitrary, not made on statistical basis. The data of particular importance is from a leprosy colony located in North Bombay representing a hyperendemic situation and a normal slum adjacent to this colony, movement of population between these two colonies being free. Age specific prevalence rates of leprosy after examining more than 80% of population from these colonies are compared with data derived from normal slums situated elsewhere in the city. The figures reveal varying prevalence rates marked by an increasing trend in the prevalence figures, leprosy colony representing the largest pool of infection. These figures indicate that wider statistically planned investigations on similar lines in urban areas may provide epidemiological data useful for planning control measures on a more rational basis.

Adolescent↗

An epidemiological study of leprosy disability in a leprosy endemic rural population of Pondicherry (south India).

The disability rate in this study was 16.23%. The highest disability rate of 30.76% was found in those aged 45 years and above. Disabilities were found to be more common among male leprosy patients with a disability rate of 21.05% compared to that of 11.45% found among female leprosy patients. None of the indeterminate leprosy patients showed any disabilities, whereas all the neuritic and lepromatous leprosy cases showed disabilities. The disability rate among tuberculoid leprosy patients and borderline leprosy patients were found to be 3.25% and 35% respectively. Persons whose monthly per capita income was less than Rs. 200/- constituted 93.50% of the cases with disabilities. Anaesthesia of the hand was seen in 67.4% of the cases. The mean disability index (DI-2 type) was 0.927.

Adolescent↗

Nodular leprosy of childhood and tuberculoid leprosy: a comparative, morphologic, immunopathologic and quantitative study of skin tissue reaction.

Nodular leprosy of childhood (NL) is a benign clinical variant of tuberculoid leprosy that affects breast-feeding infants and children that remained in a highly infected environment. The lesions resolve with complete healing and NL has been considered a manifestation of allergy and congenital immunity to Mycobacteria leprae. We studied the tissue reaction, Mycobacterial antigen frequency, and the lymphocyte subsets (CD45RO+, CD4+, CD8+, B, NK), dendritic cells (epidermal CD1a+ cells and S100+ dermal dendrocytes), and macrophages in skin lesions of a clinically well characterized NL group (N = 11). Results were compared to children (N = 23) and adults (N = 24) with classical tuberculoid leprosy. NL lesion histopathology was characterized by dense granulomatous inflammatory reaction, with a greater number of confluent tubercles when compared to the other groups. Neural compromise was seen in all biopsies. The frequency of Mycobacterium antigen was similar in all groups. The population of CD45RO+, CD4+ and CD8+ T lymphocytes, natural killer cells, B lymphocytes, CD1a+ epidermal cells, and macrophages of NL lesions did not differ from the other groups. The number of S100+ dermal dendritic cells of the NL group was smaller than that of the adult group, although it did not differ from the other group of children. Except for the confluent tubercules, our data could not disclose any other difference in the tissue reaction of NL, in spite of its peculiar clinical features and evolution when compared with the classical tuberculoid leprosy. The localization of NL lesions may be the result of the intimate skin contact with lepromatous parents or relatives, in areas such as cheeks, arms, buttocks, and limbs, and the innoculation of M. leprae into skin may strongly stimulate cell mediated immunity (CMI) against the bacilli. These circumstances might explain the good CMI response leading to high resistance, stability, and auto-resolution of nodular leprosy of childhood.

Adolescent↗

Leprosy type 1 reaction as the first manifestation of borderline lepromatous leprosy in a young native German.

While leprosy is usually a chronic disease, leprosy reactions may lead to acute problems. These reactions most often occur after initiation of therapy, but can also develop before treatment. Leprosy rarely presents with a reaction. We describe a German patient who presented in this unusual way in order to demonstrate the various tools used to confirm the diagnosis. A young German woman suddenly developed progressive functional loss of the left hand and within a few weeks an increasing number of erythematous macules and nodules appeared. Histological examination of a skin biopsy revealed tuberculoid granulomas, some located around small nerves; acid-fast bacilli were detected microscopically and DNA from Mycobacterium leprae was identified by polymerase chain reaction in the biopsy and a nasal swab; serological tests were positive. The disease was classified as borderline lepromatous leprosy. The acute neuritis followed by skin lesions represented a leprosy type 1 reaction in which the immune system reacts to bacilli previously unrecognized in nerve tissue, both in nerve and skin.

Acute Disease↗

Use of a whole blood assay to evaluate in vitro T cell responses to new leprosy skin test antigens in leprosy patients and healthy subjects.

Development of an immunological tool to detect infection with Mycobacterium leprae would greatly benefit leprosy control programmes, as demonstrated by the contribution of the tuberculin test to tuberculosis control. In a new approach to develop a 'tuberculin-like' reagent for use in leprosy, two new fractions of M. leprae depleted of cross-reactive and immunomodulatory lipids- MLSA-LAM (cytosol-derived) and MLCwA (cell wall-derived)-have been produced in a form suitable for use as skin test reagents. T cell responses (interferon-gamma (IFN-gamma) and lymphoproliferation) to these two new fractions were evaluated in a leprosy-endemic area of Nepal using a simple in vitro whole blood test. The two fractions were shown to be highly potent T cell antigens in subjects exposed to M. leprae-paucibacillary leprosy patients and household contacts. Responses to the fractions decreased towards the lepromatous pole of leprosy. Endemic control subjects also showed high responses to the fractions, indicating high exposure to M. leprae, or cross-reactive mycobacterial antigens, in this Nepali population. The new fractions, depleted of lipids and lipoarabinomannan (LAM) gave enhanced responses compared with a standard M. leprae sonicate. The cell wall fraction appeared a more potent antigen than the cytosol fraction, which may be due to the predominance of the 65-kD GroEL antigen in the cell wall. The whole blood assay proved a robust field tool and a useful way of evaluating such reagents prior to clinical trials.

Adult↗

IgA and IgM antibodies against Mycobacterium leprae in cord sera and in patients with leprosy: an indicator of intrauterine infection in leprosy.

A solid-phase radioimmunoassay was developed for demonstration and quantification of IgA and IgM anti-M. leprae antibodies. IgA and IgM anti-M. leprae antibodies were demonstrated in a lepromatous serum pool, in various amounts in individual patients with lepromatous leprosy, and in lower concentration in tuberculoid leprosy and non-leprosy controls. IgA and IgM anti-M. leprae antibodies were demonstrated in cord sera from babies of mothers with leprosy. The reliability of fetal IgA and IgM antibody synthesis as an indicator of intrauterine infection in leprosy is discussed.

Antibodies, Bacterial↗

Leprosy. XII. T-cell subsets in lepromatous leprosy.

The authors quantitated T-rosette-forming cell (TRFC) and T-cell subsets (T mu, T gamma) in the peripheral blood of twenty patients with lepromatous leprosy. The results obtained in their studies are as follows: (1) They reconfirmed the low levels of TRFC in patients with lepromatous type of leprosy; (2) T-cell subsets, both T mu (helper) and T gamma (suppressor) cells, showed lower levels in all patients with lepromatous leprosy than mean values of normal healthy controls; (3) The degree of decreased levels of T mu cells (96%) was more severe than other parameters TRFC (70%) and T gamma cells (47%) in all patients with lepromatous leprosy; and (4) It may be concluded that the alteration of the T-cell subset, T mu-cells, reflects a more fundamental abnormality than TRFC aberration in demonstrating the impairment of cell-mediated immunity in patients with lepromatous leprosy.

Adolescent↗