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Demonstration of mycobacterial antigens in leprosy tissues.

Biopsies from 69 patients with leprosy were stained to demonstrate mycobacterial antigens using immunoperoxidase methods. The same biopsies were cut and stained using Fite-Faraco, TRIFF and hematoxylin-eosin for classifying the patients and to demonstrate mycobacteria. Since M. leprae and BCG show extensive antigenic cross reactions, anti-BCG antibodies were used as primary antisera to demonstrate cross-reacting antigens of M. leprae. Cross-reacting mycobacterial antigens were, thus, found in all LL and BL leprosy patients. Eight out of 10 patients with indeterminate leprosy had mycobacterial antigens and 17 out of 19 BT leprosy patients were positive for antigens. In general, in the BT patients the presence of the antigen was related to the host tissue reaction; this relationship was found in only half of the patients with indeterminate leprosy studied. During ENL mycobacterial antigens were found both intra- and extra-cellularly in the inflammatory infiltrate, but the polymorphonuclear leukocyte infiltration was seen only around the extracellular perivascular antigen. In reversal reaction, the inflammatory response was towards extracellular mycobacterial antigens. After this reaction there were no antigens demonstrable.

Animals↗

The distribution of leprosy in Zambia.

The distribution of leprosy in Zambia is analysed on a district basis. High density areas are identified and it is suggested that genetic (tribal) factors may be relevant. It is shown that the treatment of leprosy patients has moved away from largely church-related institutions to Government Rural Health Centres. In spite of the urban drift, leprosy remains essentially a rural problem in Zambia. Differences in provincial prevalence rates for leprosy in Zambia have been recorded in previous Annual Reports of the Ministry of Health. However, an analysis of prevalence rates at a District level appears not to have been undertaken previously. It was felt this would prove of interest and be of value both for future planning of leprosy services and research.

Humans↗

Estrogen excretion in pregnant women with leprosy: evidence of diminished fetoplacental function.

Estrogen excretion was assayed in 64 women with leprosy and 15 healthy control women. The mean estrogen excretion was lower in women with leprosy than in controls and the incidence of subnormal estrogen values was higher in the leprosy patients than in the controls. There was an association between infant birth weight and frequency of subnormal estrogen excretion. These features were most marked in women with lepromatous leprosy and are further evidence of diminished fetoplacental function in women with leprosy.

Birth Weight↗

Borderline tuberculoid leprosy following BCG vaccination. A case report.

Borderline tuberculoid leprosy was diagnosed clinically and histologically in a four year-old boy about 6 months after intradermal vaccination with BCG. His mother reported that a lesion began to appear above the vaccination site on the arm 2 weeks after the vaccination, and a second lesion appeared on the chin 2 months later. Responses in the lymphocyte transformation test to sonicated Mycobacterium leprae, BCG, and to PPD were consistent with a tuberculoid leprosy infection. Precipitation of BT leprosy by intradermal BCG infection may possibly represent the overcoming of a phase of primary suppression in an individual who might otherwise have progressed toward lepromatous leprosy. The implications of this hypothesis for the planning of a controlled trial of an anti-leprosy vaccine are discussed.

BCG Vaccine↗

Leprosy and female reproductive organs.

Thirty-five adult female patients with bacillary positive leprosy were studied to determine its effect on menarche, menstrual cycle, fertility, and menopause. Endometrial biopsies studied in 26 patients showed no evidence of leprosy bacilli granuloma or tubercle bacilli on culture. Menstrual blood examined in six patients with bacillemia did not reveal leprosy bacilli. Products of conception examined from two patients were negative for granulomata or leprosy bacilli. Leprosy was found to have no direct effect on menarche, menstruation, fertility, and menopause.

Endometrium↗

A study of cell mediated immunity in leprosy.

This paper presents a review of 123 cases of leprosy of different clinical types as regards to their status of cellular immunity. These 123 cases included 41 fresh cases, 18 cases of reaction and 64 cases of leprosy taking antileprosy treatment. Out of 41 untreated cases only 11 turned up for follow up and their lymphoblastic transformation was repeated 4 to 6 months after initiating the treatment. It was observed that cell mediated immunity as expressed in terms of percentage of blast cells is definitely depressed in leprosy, most in LL and least in TT. There is a definite increase in the percentage of blast cells after taking antileprosy treatment. The rise in percentage of blast cells and hence cellular immunity is relatively more in patients treated with Lamprene as compared to those treated with DDS. Reactions also have impact over immunity in leprosy. Thus, most of the patients with ENL show higher values for blast percentage as compared to those with lepra reaction. It appears that serial lymphocyte cultures if done in all cases of leprosy undergoing treatment will help in assessment of individual progress.

Adolescent↗

Immunological status of maculoanaesthetic leprosy: leucocyte migration inhibition test as a measure of cell mediated immune response.

M. leprae-specific cell-mediated immune responses were studied in 36 Maculoanaesthetic (MA) leprosy patients using Leucocyte Migration Inhibition Test (LMIT). 21-Tuberculoid, 13-Indeterminate, 16-Borderline, 13-Lepromatous and 20-Healthy controls were also studied for comparison. Highly significant differences (p less than 0.001) in the mean Migratory Indices (M.I.) were found between MA leprosy type and each of the other leprosy type or control group. The results support the concept that MA type forms a distinct form of leprosy from tuberculoid type or any other type of leprosy.

Antigens, Bacterial↗

Liver lesions in reactional states in leprosy.

Liver biopsy was done in 21 adult patients of leprosy in acute reaction. They included 10 of lepromatous leprosy, seven of tuberculoid leprosy and four of dimorphic leprosy. Except for a single case of tuberculoid leprosy all showed granulomatous lesions of varying sizes and frequency, in the liver. The lesions appeared to be unique for reaction and immunologically-based. The sequence of events appeared to be: (1) Immunologically-mediated alteration of Kupffer cells with adhesion of lymphocytes and polymorphounuclear leucocytes (2) Small granulomas of proliferating Kupffer cells, lymphocytes and polymorphs. (3) In some cases. formation of larger granulomas with breaking down of reticulin and liver cell necrosis.

Female↗

Recognition of Mycobacterium leprae antigens with antibodies present in sera from patients with lepromatous leprosy.

A great diversity of antigens from Mycobacterium leprae have been described. One practical approach should be to utilize them as markers to indicate when a household contact is at risk of becoming infected and then moving to an active form of leprosy. For this purpose, sonic extracts of M. leprae were fractionated in 10% SDS-PAGE under reducing conditions. The fractionated proteins were then transferred to nitrocellulose sheets and incubated with sera from lepromatous leprosy cases, their contacts, and normal subjects in order to reveal the frequency of antigen recognition of each set of sera. The results showed that sera from lepromatous leprosy patients frequently recognized two proteins, one of approximately 28 kDa and the other of approximately 65 kDa, when compared with the sera from normal subjects. The contacts frequently recognized an approximately 16-kDa antigenic band, while sera from normal subjects recognized one protein of approximately 18 kDa. According to the results, the four recognized proteins from M. leprae can be considered markers of the above conditions (approximately 65 kDa, approximately 28 kDa for lepromatous leprosy, approximately 16 kDa for contacts, and approximately 19 kDa for normal subjects). From these, an easy serological test, such as an ELISA, can be developed to predict if a contact is moving toward lepromatous leprosy before detection of the actual clinical signs or symptoms.

Adult↗

IgG subclass antibody to Mycobacterium leprae 18,000 MW antigen is restricted to IgG1 and IgG3 in leprosy.

IgG subclass responses to Mycobacterium leprae 18,000 MW recombinant antigen (18K) were determined in sera from untreated leprosy patients using an ELISA-based assay with specific monoclonal antibodies. Antibodies to M. leprae 18K were restricted to IgG1 and IgG3 antibodies with higher seropositivity in lepromatous patients (25.5% for IgG1 and 12.8% for IgG3) compared to patients with tuberculoid disease (11.5% for IgG1 and 5% for IgG3). No significant antibody response was detectable in IgG2 and IgG4 in patients with either lepromatous or tuberculoid leprosy. The selective production of antibodies in IgG1 and IgG3 subclasses could not be related to polyclonal activation in these subclasses as all IgG subclasses showed similar elevated levels at the polyclonal level. The major difference noted between lepromatous and tuberculoid leprosy patients with the IgG subclass antibody response was a strong linear correlation between IgG1 and IgG3 responses to M. leprae 18K in lepromatous patients (r = 0.703, P < 0.001) but not in tuberculoid leprosy patients (r = 0.007, P > 0.10) which may be related to immunoglobulin class switching of IgG3 to IgG1 rather than selective shifts in T-helper subsets. Our results therefore, do not support the hypothesis that activation of Th2 cells occurs in lepromatous leprosy; this issue needs further examination.

Antibodies, Bacterial↗

Macrophage function in leprosy.

The macrophage function in patients with leprosy was assessed by estimating histochemically the acid phosphatase activity in skin biopsies and by assessment of phagocytic and lytic capability of in vitro cultured macrophages derived from peripheral blood monocytes, challenged with live M. leprae. Acid phosphatase was demonstrated in skin biopsies of different groups of leprosy patients classified according to the Ridley and Jopling scale. The degree of acid phosphatase positivity was correlated with clinical spectrum, Bacterial and Morphologic Indices and treatment status. Peripheral blood monocytes from patients with leprosy, either tuberculoid or lepromatous, were cultured in monolayers and challenged with M. leprae. The phagocytosis and lysis of mycobacteria by macrophages was observed at different time intervals from the 1st to the 28th day. The morphology of the macrophages in different types of leprosy was also studied. The results suggest that macrophages from patients with either tuberculoid or lepromatous leprosy are not by themselves capable of lysing live M. leprae. Live M. leprae injected into the foot pad of Wistar strain of rats evoked similar responses on the tenth day, in normal and protein deficient animals.

Acid Phosphatase↗

Electrophoresis and immuno electrophoresis in leprosy.

50 cases of leprosy belonging to various subgroups i.e. 10 tuberculoid, 25 lepromatous leprosy, 10 lepra reaction, 5 dimorphic leprosy, and 25 cases or normal individuals were subjected to agar gel electrophoresis. The slides were scanned by densitometry. It showed profound departure from normal in various fractions of electrophoretic patterns. All of them showed rise of gamma globulin. Albumin was markedly decreased in lepromotous leprosy and lepra reaction. In dimorphic leprosy Alfa-1 was decreased. Qualitative immuno electrophoresis was done by using antihuman serum raised in the laboratory, by immunising rabbits. It revealed changes in IgM and IgG arcs. Results are discussed and tried to explain on immunological derangement.

Alpha-Globulins↗

Low predictive value of PGL-I serology for the early diagnosis of leprosy in family contacts: results of a 10-year prospective field study in French Polynesia.

In 1983, a cohort study to follow up the family contacts of leprosy cases was implemented in French Polynesia to assess the usefulness and applicability of phenolic glycolipid-I (PGL-I) serology in a leprosy control program. A total of 1201 contacts (666 females, 535 males) have been included in the study. The IgM anti-PGL-I seroprevalence determined on the initial sera was 17%. It was significantly higher among females than males (20% vs 15%, p = 0.02). From 1983 to 1992, 4 out of 204 (2%) anti-PGL-I seropositive contacts developed the disease (1 indeterminate, 1 BT, 1 BL, 1 LL) compared with 10 out of 997 (1%) seronegative contacts (4 indeterminate, 3 BT, 1 BB, 2 TT). Of these 10 patients, only 3 (2 indeterminate, 1 BT) converted to seropositivity when leprosy was diagnosed. The risk of developing leprosy was not significantly higher among seropositive than among seronegative groups (2% vs 1%, p = 0.2). A PGL-I circulating antigen test performed on 216 selected sera at entry into the trial showed a higher antigen prevalence when the antibody level was higher. PGL-I antigen was detectable in 5 of 12 patients tested prior to diagnosis (1 LL, 1 BL, 3 indeterminate). The median time to externalize the disease was not significantly different among antibody-positive and -negative contacts (17 vs 25 months, p = 0.3). The relative risk of developing leprosy for contact individuals was 30.8 times that of noncontacts, and 15% of the total new cases detected between 1983 and 1992 emerged from the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intrafamilial transmission of leprosy in Vellore Town, India.

A hospital-based study was done from 1968 to 1991 to determine the risk and extent of intrafamilial transmission of leprosy in relation to the characteristics of the index cases and contacts in urban areas in India. Families were examined by doctors annually. Skin smears were done for contacts of multibacillary (MB) leprosy patients. Person years of follow up were computed for each contact and used as the denominator for computation of incidence rates. Specific rates were computed by age, sex, type of leprosy, smear in index cases, age at registration, and sex of contacts. Of the 120 index cases (81 males, 39 females) 44% were MB; 410 contacts (186 males, 224 females) and 14 co-prevalent cases were registered. The cumulative years of follow up was 2725 years. Fourteen contacts developed the disease (9 TT, 3 indeterminate, and 2 BT); 85.7% were in the 0-14 age group; 12 of 14 patients were detected to have leprosy during the first 5 years. The incidence rate (IR) was 5.1/1000 (males 5.15, females 5.12). The IR was 7.3/1000 and 2.3/1000 among contacts of MB and paucibacillary leprosy patients (p < 0.05). The IR in multiple-case families was 1.8. The importance of active surveillance by a hospital-based survey is emphasized. It should be designed to focus on children younger than 15 years and should be limited to 5 years of follow up.

Adolescent↗

Serum zinc, sodium, calcium, magnesium and potassium levels and standard diet in leprosy patients.

Serum zinc levels were estimated in different types of leprosy by means of the atomic absorption spectrophotometry method in 64 leprosy patients, comprising of tuberculoid tuberculoid (TT) (5), borderline tuberculoid (BT) (6), borderline borderline (BB) (10), borderline lepromatous (BL) (13), lepromatous lepromatous (LL) (14) and burnt-out leprosy (BO) (16). These findings were evaluated in comparison to 86 normal control subjects who were served the same standard diet. Serum zinc levels were significantly low in the total leprosy group. The findings of this study are of clinical importance as zinc deficiency can be one of the factors involved in suppression of cell-mediated immunity (CMI) in lepromatous leprosy. This again has a bearing on the management of wounds and wound healing. This study also reveals that altered levels of the serum elements (eg. calcium and sodium) have a direct association with the disease and not with food deprivation.

Calcium↗

Incidence rates of leprosy in Karonga District, northern Malawi: patterns by age, sex, BCG status and classification.

This paper describes incidence rates by age, sex, prior BCG status and classification in Karonga District, northern Malawi. New cases (489) were identified among 83,500 individuals followed for an average of 5 years (1.12 cases per 1000 person years). Only 29 (6%) of the incident cases were multibacillary. Incidence rates generally were higher among females than males, and increased steadily with age. Although the highest incidence rates of disease were recorded among young adults without BCG scars (males 15-19; females 20-24), these peaks were less dramatic than those reported among young adults in The Philippines and Norway. In the absence of historical data and data on infection status, it is not possible to assess to what extent these peaks may reflect either greater exposure or greater susceptibility to disease among adolescents or young adults. The incidence rates of leprosy among individuals with a prior recorded BCG scar were approximately half those of individuals lacking a scar, at all ages. Since BCG had been introduced into this population only during the 1970s, this provides strong evidence for the effectiveness of BCG when given to adults. It was estimated that past vaccination of approximately 40% of the district population had reduced the overall incidence rate of leprosy by 18%, and that this impact would increase with aging of the vaccinated cohorts. A retrospective examination of the detailed records of initial examinations revealed that 62 (13%) of the incidence cases were recorded as having skin hypopigmentation or blemishes, at the site of subsequent confirmed leprosy lesions, several months or years before they were suspected of having leprosy. The nonspecificity of these lesions, some of which were probably attributable to Mycobacterium leprae infection, highlights the difficulty of diagnosing leprosy in its earliest forms.

Adolescent↗

Ambiguities in leprosy histopathology.

This paper presents the percentage of definite or suggestive evidence present in 482 biopsies from different types of leprosy. The presence of acid-fast bacilli (AFB) and nerve involvement were taken as definite features for a diagnosis of leprosy, and infiltration of the dermal appendages, neurovascular bundles and dermis by granuloma cells and lymphocytes were regarded as suggestive signs of leprosy. Using these criteria, all cases were categorized into three groups having definite, suggestive, or no signs of leprosy. The results showed definite and suggestive features in 72.2% and 14.1% of the cases, respectively. The remaining 13.7% had none of these signs. These cases were mostly healed lesions. Large, epithelioid cell granulomas without any nerve element present and healed cases proved difficult for a definite diagnosis. Emphasis is placed on searching for residual nerve elements in AFB-negative sections because this increases the certainty level of the diagnosis. Also, it is suggested that for uniformity of understanding and reporting, terminologies need to be narrowed down and restricted to only definite, suggestive, or no diagnosis of leprosy.

Biopsy↗

Cell-mediated immunity in amyloidosis secondary to lepromatous leprosy.

Cell-mediated immunity in lepromatous leprosy patients with and without amyloidosis has been studied. Amyloidosis occurred mostly in patients with a history of recurrent erythema nodosum leprosum (ENL) reactions. For this reason, two control groups of leprosy patients were included, one having a history of recurrent ENL and the other little or no ENL. The lack of responsiveness to lepromin in vivo and in vitro, characteristic of lepromatous leprosy, was not altered by the presence of amyloidosis or a history of ENL. No significant difference between the patient groups was observed in the response to PPD in vitro, but skin reactivity to PPD was significantly lower in the patients with amyloidosis than in those without amyloidosis. In contrast, the PHA responses of patients with amyloidosis were significantly higher than those of control patients without a history of ENL, but not significantly different from those of control patients with a history of recurrent ENL. Lepromatous leprosy patients who develop amyloidosis thus appear to belong to a group, susceptible to repeated attacks of ENL, whose PHA responses are higher than those of other lepromatous leprosy patients. The lower skin reactivity to PPD observed in the amyloid group may reflect a general impairment in delayed cutaneous hypersensitivity.

Adolescent↗