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Induction of lepromin positivity by a candidate anti-leprosy vaccine Mycobacterium w in lepromin negative healthy contacts of multibacillary leprosy patients.

In a hospital based study, 362 household contacts of multibacillary leprosy patients were screened for evidence of leprosy and 54 (14.9%) were found to be having leprosy. The remaining 308 apparently healthy contacts were lepromin tested and 109 (35.4%) were observed to be negative to Mitsuda lepromin. M.w vaccine was administered intradermally to 95 of these 109 lepromin negative contacts. Sixty eight of them could be retested for lepromin A reactivity. Fifty six (82.35%) manifested lepromin conversion. The twelve subjects who did not show lepromin conversion, received a second dose of the vaccine, and eleven subsequently became lepromin positive. The overall lepromin conversion rate was thus 98.5% (67 out of 68). Follow-up of these contacts upto a period of 30 months did not demonstrate reversion of lepromin positivity back to negativity status. No untoward effects of vaccination were observed except for local ulceration at the site of vaccine administration.

Adolescent↗

Depressive effect of serum from patients with leprosy on mixed lymphocyte reactions. Influence of anti-leprosy treatment.

Mixed leucocyte cultures, from two normal donors, were set up in media containing human serum from one of the following sources: (a) a pool of normal group AB donors; (b) Chinese, Malay or Indian patients with untreated leprosy; (c) the same patients after effective anti-leprosy treatment; (d) control Chinese, Malay or Indian subjects. Transformation was estimated by measuring the incorporation of tritiated thymidine in the last 24 hr of a 7-day culture period. Transformation was impaired in sera from treated lepromatous patients, but was less impaired or not impaired at all in sera from treated lepromatous patients. The loss of depressive activity after treatment was more marked in Chinese and Indian than in Malay patients. Transformation was also impaired, though to a lesser extent, in sera from patients with untreated tuberculoid leprosy; it was still impaired in sera from treated tuberculoid patients. There was no evidence of specificity in impairment of mixed lymphocyte reactivity and lymphocytotoxic antibodies appeared to play no role. The incidences of hepatitis B antigen and antibody and of anti-nuclear factor were not notably high.

Adolescent↗

Leprosy deformities. II. As parameters to monitor the effectivity of leprosy control programme.

Leprosy deformities have been considered as the main reason for dehabilitation and social ostracism. Prevention of deformities is considered as one of the most important objectives of leprosy control programme. In present work based on deformity status, efforts have been made to evolve new parameters and their possible application in assessment of leprosy control programme.

Age Factors↗

Undernutrition and lepromatous leprosy. Serum vitamin A and E levels in leprosy spectrum.

Serum vitamins A and E were estimated by spectrophotocolorimetric methods in 67 leprosy patients comprising 9 BT, 10 BB, 15 BL, 27 LL, including 12 Histoid cases. These findings were evaluated in comparison to 55 normal subjects serving as controls. A significant reductions in the mean serum levels of Vitamins 'A' and 'E' were observed in the leprosy groups as compared to normal controls. These findings are of considerable importance and need to be taken note of in the light of delineating these alterations to the cause or effect of the disease. As far as we know, this is the first report describing serum levels of Vitamins 'A' and 'E' in the leprosy spectrum.

Adolescent↗

A sample survey of leprosy in the ELEP Leprosy Control Project, Dharmapuri, Tamil Nadu.

A sample survey of the Dharmapuri Leprosy Control Project was undertaken in 1983; a population of 60855 was enumerated out of which 51205 was examined. The sampling procedure which was followed consisted of stratifying the sub-centres according to prevalence and classifying the villages by the size of the population. Villages were selected by random allocation. 10 leprosy inspectors participated in the survey examining 626 to 774 persons per day. 859 active cases were detected giving a prevalence of 16.77 per thousand. The child prevalence was 6.19 per thousand. The number of lepromatous and BL cases detected were 70 giving an infectivity rate of 8.15%. The prevalence of leprosy as found in the last survey conducted in the different areas in the project approximate to those of the sample survey. Therefore it could be said that the prevalence has decreased in this project from 19.94 per thousand as observed in the first survey. The child prevalence has likewise decreased from 9.40 to 4.09 in the project.

Adult↗

Immunological studies in leprosy--II: Study of lymphoblast transformation to PHA in different types of leprosy patients.

Ninety cases of different types of leprosy were studied for lymphoblast transformation response using PHA-M. The difference of percentage was statistically analysed and found to be highly significant when total leprosy cases were compared with control cases and with different types of leprosy cases (P = less than .005), except control and TT where it was significant only (P = less than .05). The difference between TT and other types was also calculated and has been observed to be highly significant (P = less than .005). There was gradual decrease in lymphoblast transformation percentage from tuberculoid pole to lepromatous pole.

Female↗

Impact of knowledge of leprosy on the attitude towards leprosy patients: a community study.

NLEP, through its survey-education-treatment (SET) pattern, attempts to educate the community members about the scientific facts of leprosy with the view to improve their knowledge leading to a more positive attitude towards the leprosy afflicted. This paper explores the impact of knowledge on the attitudes of 1199 community members drawn from two States, Andhra Pradesh and Orissa, towards leprosy. The results show that, overall, a high knowledge level did not necessarily generate positive attitudes. There was a general negative attitude despite 35% to 50% of the respondents having high knowledge level. There were, however, situations in which a high level of knowledge helps to have positive attitudes. These situations differ in the two states studied.

Adolescent↗

"Pseudoneoplastic" leprosy. Leprosy revisited.

A 70-year-old Italian man with a history of squamous cell carcinoma of the lung presented with a nodular skin eruption. He had traveled extensively in India and Sri Lanka. The nodules were well demarcated and measured up to 3.5 cm in diameter. Histologically, there was a proliferation of spindled and polygonal cells with focal and relatively inconspicuous cytoplasmic vacuolation. A macrophage-monocyte lineage for the cells was confirmed by paraffin section immunohistochemistry, using the monoclonal antibodies anti-CD45, MAC-387, KP-1, UCHL-1, MT-1, L26, and MB2. Infiltrating borders, extension of the lesion into the subcutis, and involvement of small dermal nerves and eccrine glands initially suggested the possibility of a "histiocytic" neoplasm of indeterminate biological potential. However, air-dried and Giemsa-stained material from a fine-needle aspirate of one cutaneous nodule showed needle-shaped intracellular "negative images," and acid-fast stains revealed a large number of intracytoplasmic bacilli in virtually all of the vacuolated lesional cells. Furthermore, a second skin nodule that was excised 3 weeks after initial presentation showed the typical morphology of lepromatous leprosy. The clinicopathologic features of this case demonstrated several similarities with those of so-called "histoid" leprosy. Unusual morphologic variants of leprosy need to be considered in the interpretation of unusual "histiocytic" infiltrates in order to avoid a mistaken diagnosis of neoplasia, regardless of the geographic locale in which the patient is evaluated.

Aged↗

Suppression of tumour necrosis factor-alpha expression in leprosy skin lesions during treatment for leprosy.

The expression of tumour necrosis factor (TNF)-alpha in leprosy skin lesions was examined before and during successful treatment in a patient with borderline lepromatous leprosy. Before treatment, immunohistochemical staining of a skin biopsy specimen showed diffuse TNF-alpha deposits in granulomas and significant TNF-alpha deposits on infiltrated mononuclear cells. After 1 year's treatment, the skin lesions exhibited a reduction in granulomas, and a concomitant reduction in deposits of TNF-alpha. Furthermore, the level of expression of TNF-alpha messenger RNA, as examined using a reverse transcriptase-polymerase chain reaction method, was reduced markedly after treatment. These findings provide evidence for a correlation between the expression of TNF-alpha and disease activity suggesting that TNF-alpha is a useful prognostic indicator for inflammation in leprosy.

Aged↗

Fractionation, characterization and diagnostic potential of circulating leprosy antigens isolated from sera of lepromatous leprosy patients.

Circulating antigen was isolated from lepromatous sera by ammonium sulfate precipitation. The protein fraction between 36% and 75% ammonium sulfate was reactive with leprosy sera. Further fractionation of Ultrogel AcA 34 gel filtration column gave four protein fractions, CLA1, CLA2, CLA3 and CLA4. CLA1 and CLA2 showed antigenic activity. On SDS-PAGE analysis and elution of the protein fractions, CLA1-7, CLA2-1 and CLA2-7 were found to be reactive with leprosy sera. On evaluating the diagnostic utility of these fractions, CLA1-7 could detect IgG antibodies in 80% of the lepromatous (LL) and in 40% of the tuberculoid (TT) serum samples. Fraction CLA2-1 reacted with IgM antibodies in 80% of the LL and TT patients; fraction CLA2-7 reacted with IgM antibodies in 70% of the LL and TT sera. Biochemical characterization indicated that CLA1-7 was a glycoprotein while CLA2-1 and CLA2-7 were lipoproteins in nature. When tested by an inhibition ELISA, fraction CLA2-7 inhibited the binding of anticeramide antibodies to a ceramide-coated plate while thin-layer chromatography of fractions CLA2-1 and CLA2-7 showed a spot with an Rf value similar to that of standard ceramide. This study thus shows for the first time the presence of ceramide in circulating leprosy antigen.

Animals↗

The occurrence of reactions and impairments in leprosy: experience in the leprosy control program of three provinces in northeastern Thailand, 1987-1995 [correction of 1978-1995]. III. Neural and other impairments.

AIM: This the third paper in a series of three papers on the occurrence of reactions and impairments in leprosy in Thailand, and focuses on the prevalence and incidence of neural and other impairments in leprosy. STUDY DESIGN: A population-based, prospective cohort study. STUDY SUBJECT: All 640 newly diagnosed and registered leprosy patients in three provinces of northeastern Thailand between October 1987 and September 1990 were included [420 paucibacillary (PB) and 220 multibacillary (MB)]. This group of patients was followed up until the end of 1995. METHODS: Clinical data; data on the sensibility and motor function of eyes, hands and feet, and data on wounds and bone loss were obtained where appropriate. The occurrence of neural and other impairments at first examination, during treatment and during surveillance was ascertained. RESULTS: The relationship between impairment prevalence (grade 2 of the combined PB and MB groups and grades 1 and 2 together of the combined PB and MB groups) and duration of disease (before diagnosis) was found to be statistically significant. Increased delay in detection led to increased problems of impairments. Too many patients still develop new/additional impairments while on treatment and thereafter. The incidence of nerve function impairment (NFI) among patients without impairments at first examination while on treatment was 1.7 [ 95% confidence interval (CI) 0.45-4.4] per 100 person-years at risk (PYAR) for the PB group and 12 (CI 8.4-17) per 100 PYAR for the MB group. Additionally, 2% of the PB and 11% of the MB patients who already had impairments at first examination developed new NFI while on treatment. The outcome, comparing the first examination with the last examination during/after surveillance [changes in the voluntary muscle test (VMT), the sensory test (ST), wound count and bone loss], indicated that of the PB patients 3.7% improved, 3.7% got worse and 3.9% kept the same impairment; of the MB patients 19% improved, 18% got worse and 2.9% kept the same impairment. During treatment most of the new/additional impairments were due to new/increase in NFI; during surveillance slightly more than 50% were due to new/increase in NFI. Eighty-three percent of the MB patients without impairments at first examination who developed NFI during treatment improved (completely or partially) after receiving prednisolone. Only 62% of the MB patients with a grade 1 impairment at first examination and who developed a severe reaction or recent silent neuropathy improved after receiving prednisolone. There is a need for an indicator to measure new/additional impairments while on treatment and thereafter. It is proposed to measure changes in impairment by measuring changes in VMT, ST, wound count and bone loss.

Adolescent↗

Immunologic defects in leprosy patients. II. Interleukin 1, interleukin 2, and interferon production in leprosy patients.

The capabilities of monocytes and lymphocytes in peripheral blood mononuclear leukocytes (PBML) to produce interleukin-1 (IL-1), IL-2, and interferon (IFN), respectively, were evaluated in various types and treatments of leprosy patients. IL-1 production in response to lipopolysaccharide was significantly lower in LL, BL, BB, and BT patients than in normal controls. However, there were no differences in IL-1 levels between TT patients and normal controls. The percentages of nonspecific-esterase-positive cells adhering to the plastic surfaces were not different in LL, BB and TT patients when compared to normal controls. However, they were significantly higher in BT and BL patients than in normal controls. When PBML from leprosy patients were stimulated with concanavalin-A (ConA) for IL-2 production, there were no differences in the IL-2 levels in treated BL/LL, untreated BL/LL, treated BT/TT, and untreated BT/TT patients compared to normal controls. Similar results were obtained when PBML were stimulated with phytohemagglutinin-P (PHA-P). However, when purified protein derivative (PPD) was used as the stimulating agent, there were significantly lower IL-2 levels in treated BL/LL, untreated BL/LL, treated BT/TT, and untreated BT/TT patients when compared to normal controls. There were also lower IL-2 levels in untreated BL/LL and BT/TT patients compared to treated BL/LL and BT/TT patients, respectively. PBML were stimulated with PHA-P or ConA for IFN production.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Do human leukocyte antigens have a role to play in differential manifestation of multibacillary leprosy: a study on multibacillary leprosy patients from north India.

118 multibacillary leprosy patients with differential manifestations were studied for the antigens they expressed at MHC loci to investigate the role of human leukocyte antigens in the differential response to the same causative agent. While the lepromatous leprosy (LL) patients showed a significant increase of Bw60, DR2, DRw8 and DQw1, borderline lepromatous (BL) patients had Bw52, DR9 and DQw7 significantly more often as compared to the normal controls. A comparison of LL, BL and mid-borderline (BB) patients showed a significantly higher frequency of Bw60 in LL patients as compared to the BL. However, Bw52, Bw53, DR9 and DQw7 were found significantly more often in the BL patients as compared to the LL patients but the difference failed to reach significance after pc. A comparison of HLA antigens in BB patients with those of either the LL or BL patients did not show any significant differences.

Antigens, Bacterial↗

Ultrastructural characteristics of macrophages in dermal leprosy granulomas: macrophages in leprosy granulomas.

The characteristics of the cells of mononuclear phagocyte series (MPS) in the dermal granulomas of tuberculoid and lepromatous leprosy were studied by elereron microscopy. In the tuberculoid granulomas, majority of the cells of MPS (epithelioid cells) showed a distinct appearance. They were seen in close association with a large number of activated lymphocytes. The cells of MPS had a prominent nucleus. Their cytoplasm contained mainly rough endoplasmic reticulum, developed golgi and was free of M. leprae or its products. In contrast, the cells of MPS (macrophages) in lepromatous leprosy had a large nucleus. Their cytoplasm contained mainly whole M. leprae organisms/its phagocytosed products and rough endoplasmic reticulum. There was paucity of lymphocytes in these granulomas. These observations support the view that the cells of MPS in the tuberculoid granulomas may be secretory while those in the lepromatous granulomas were phagocytic.

Granuloma↗

Two unusual nerve abscesses--lepromatous leprosy and pure neural leprosy: case reports.

We report two cases of nerve abscesses, one suffering from lepromatous leprosy (LL) and the other from tuberculoid neural leprosy. Neither had any signs of reactions. Both were untreated cases. Surgical nerve decompression and systemic prednisolone had resolved the nerve abscess in the first case, whereas the second one responded only to surgical nerve decompression. The unusual nature of clinical presentation of nerve abscess has been outlined.

Abscess↗

Immunohistological localization of mycobacterial antigens within the peripheral nerves of treated leprosy patients and their significance to nerve damage in leprosy.

The presence and distribution of Mycobacterium leprae-specific and cross-reacting antigens within the peripheral nerves of multidrug-treated patients with leprosy was investigated to gain a better understanding of the mechanism of nerve damage and the effect of multidrug therapy (MDT) on it. There was no specific qualitative difference in the type of antigens in the leprosy spectrum. However, our results indicate that there may be differential handling of antigens by the macrophages as compared to Schwann cells. This could play a key role in the pathogenesis of the disease. Multidrug treatment is effective in arresting the progression of the disease process as well as in reducing the viable bacterial load, both in borderline lepromatous and lepromatous (MB) and borderline tuberculoid and tuberculoid (PB) cases. However, the presence of M. leprae antigens in all the multidrug-treated MB nerve lesions and 87% of PB nerve lesions suggest that the antigens persist for a prolonged period. Hence, the risk of immunological reaction and antigen-associated silent nerve damage may continue even after majority of M. leprae were killed. The findings give further support to the view that most of the nerve damage is due to bacterial antigens.

Adolescent↗

Immunohistological analysis of in situ expression of mycobacterial antigens in skin lesions of leprosy patients across the histopathological spectrum. Association of Mycobacterial lipoarabinomannan (LAM) and Mycobacterium leprae phenolic glycolipid-I (PGL-I) with leprosy reactions.

The presence of mycobacterial antigens in leprosy skin lesions was studied by immunohistological methods using monoclonal antibodies (MAbs) to Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) and to cross-reactive mycobacterial antigens of 36 kd, 65 kd, and lipoarabinomannan (LAM). The staining patterns with MAb to 36 kd and 65 kd were heterogeneous and were also seen in the lesions of other skin diseases. The in situ staining of PGL-I and LAM was seen only in leprosy. Both antigens were abundantly present in infiltrating macrophages in the lesions of untreated multibacillary (MB) patients, whereas only PGL-I was occasionally seen in scattered macrophages in untreated paucibacillary lesions. During treatment, clearance of PGL-I from granulomas in MB lesions occurred before that of LAM, although the former persisted in scattered macrophages in some treated patients. This persistence of PGL-I in the lesions paralleled high serum anti-PGL-I antibody titers but was not indicative for the presence of viable bacilli in the lesions. Interestingly, we also observed a differential expression pattern of PGL-I and LAM in the lesions of MB patients with reactions during the course of the disease as compared with those without reactions. In conclusion, the in situ expression pattern of PGL-I and LAM in MB patients may assist in early diagnosis of reactions versus relapse.

Antibodies, Bacterial↗