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A family study of leprosy: subcutaneous amyloid deposits and humoral immune responses.

One group of 11 aboriginal families, consisting of 27 persons with leprosy and 43 unaffected family members, and a second group of 26 patients with leprosy were studied in the Northern Territory of Australia. Amyloid deposits were sought in fine needle aspirates of subcutaneous fat and serological investigations relevant to amyloidosis and to the humoral immune response were done. The study showed unexpectedly high frequencies of amyloid deposits, evidence of persisting hepatitis B virus (HBV) infection, and antibodies to smooth muscle, to skin basement membrane, and to extractable nuclear antigens (ENA). Compared with unaffected family members, patients with leprosy had increased serum alpha-lipoprotein (alpha-LP) and were more often hepatitis B surface antigen (HBsAg) carriers but, contrary to expectations, the presence of amyloid, the alpha-LP level, serum amyloid associated (SAA) protein, and the HBsAg carrier state all appeared unrelated to the type of leprosy.

Adult↗

A study of serum protein in leprosy.

Total serum protein albumin, globulin and A/6 ratio were determined in 50 patients of different types of Leprosy and 15 healthy controls. A significant elevation of total serum proteins (P < 0.001) was observed in 25 patients of Lepromatous leprosy and 10 patients of lepra reaction. No statistically significant alteration in total serum protein (P < 0.05) was observed in 15 patients of non-lepromatous leprosy. A significant fall in serum albumin with concomitant rise in serum globulin level (P < 0.001) was observed in non-lepromatous leprosy, lepromatous and patients having lepra-reaction.

Adult↗

Serology of leprosy. I. Indirect hemagglutination test with stabilized sensitized red cells.

An indirect hemagglutination (IHA) test has been described for the qualitative and quantitative detection of antibodies specific to Mycobacterium leprae. Aldehyde stabilized red cells were sensitized with a sonicate antigen prepared from M. leprae purified from armadillo liver. These cells were titrated against sera from patients with different types of leprosy, their healthy household contacts and patients with tuberculosis. Specific antibodies were demonstrated in leprous sera by IHA test after absorption of sera with M. tuberculosis and M. vaccae. All advanced forms of leprosy (LL and BL) and a variable number of other forms of leprosy (BB, BT and TT) showed a positive result with an IHA titre of 1 in 32 or above. None of the household contact sera nor sera from tuberculosis patients showed a positive IHA test. The application of the simple hemagglutination test in the immunoepidemiology of leprosy is discussed.

Antibodies, Bacterial↗

An assessment of school survey as a method of detection of leprosy cases.

The present study includes the analysis of case-control study and hospital records of leprosy patients. 26 cases of leprosy were detected through examination of 21,412 school children of 5-19 years age, attending 30 and 25 schools in urban and rural area respectively of Surat District. Matched controls of these leprosy cases were selected from their healthy class-mates by employing certain criteria. Home visits paid to these 24 cases and their controls revealed a positive family history in 50% (12/24) of affected students. Case detection rates were 17.9% and 0.0% among the contracts of affected students and their controls respectively. Out of 26 cases, 16 (61.5%) were detected for the first time (undetected cases). However, record analysis revealed that only 32.6% and 39.5% of the detected cases of school going age, were attending schools in rural and urban area respectively. School survey and contact survey of child cases, in spite of certain limitations, can be considered as a useful, cheap and rapid method for detection of leprosy cases in the community.

Adolescent↗

Serum lysozyme in leprosy.

Serum lysozyme was assessed in 43 healthy subjects and 183 leprosy patients. Significantly elevated level of lysozyme was observed in sera of leprosy patients as compared to normal individuals. The enzyme levels in leprosy of different types showed elevations in following order, Erythema Nodosum Leprosum (ENL) greater than Lepromatous greater than Borderline greater than Tuberculoid. Enzyme levels in patients with inactive stage were lower than in untreated patients. The serum lysozyme level correlated well with the activity disease in leprosy--clinically and bacteriologically. Thus the estimation of serum lysozyme can be used as one of the parameters of activity of the disease.

Adolescent↗

Denatured muscle grafts for nerve repair in an experimental model of nerve damage in leprosy. 2. Recovery of peripheral peptide-containing nerves assessed by quantitative immunohistochemical study.

A marked depletion of neuropeptide-immunoreactive nerves, a consequence of the nerve damage which is commonly found in leprosy, has been reported in peripheral tissues of leprosy patients and of a leprosy animal model. The aim of this study was to investigate peripheral reinnervation following a denatured autologous muscle graft in an animal model of leprosy nerve damage. Possible reinnervation of the foot-pad skin was studied by immunohistochemistry using antisera to the neuronal marker protein gene product 9.5 (PGP), the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and the C-flanking peptide of neuropeptide Y (CPON). The extent of the reinnervation process was assessed by image analysis quantification at different time points. At 8 weeks after muscle grafting, there were small numbers of immunoreactive nerves (p < 0.05). At 12, 16, and 20 weeks postoperatively there was a gradual increase in all immunostaining. At 20 weeks, no significant difference was found for PGP-, CGRP-, and SP-immunoreactive nerves in the epidermal and subepidermal layers compared to control (contralateral) tissue. In experimental tissue the recovery of immunoreactive nerves around sweat glands took longer (up to 12 weeks) than in other skin compartments, but after that time the recovery was rapid and at 20 weeks no difference was measured for VIP-immunoreactive nerves in comparison with controls. Around blood vessels, the recovery of CGRP- and CPON-immunoreactive fibers was slow, and at 20 weeks a difference with control samples (p < 0.01) was noted. In the same area, there was no significant difference for PGP immunoreactivity between controls and tissues at 20 weeks. In contrast, the immunoreactive nerve bundles in the dermis showed a faster recovery than nerves in other skin areas, with amounts similar to controls at 20 weeks. The significant recovery of immunoreactive nerves, in particular of those containing sensory neuropeptide, is consistent with the described functional recovery.

Animals↗

Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae.

Cytokine profiles of circulating mononuclear cells were studied with the aim of delineating T-cell subsets in leprosy patients with active disease. Using reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokine mRNA and enzyme-linked immunoassay (ELISA) for the secreted products, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied. Three antigens, native Mycobacterium leprae, a recombinant antigen LSR/A15 of M. leprae and peptide 624 spanning 58-77 amino acids of the latter, were used to induce cytokine expression and release. Half of the subjects, irrespective of the clinical type or antigen used, showed a mixed T-helper type 0 (Th0)-like cytokine pattern, with evidence of the concomitant presence of IFN-gamma and IL-4. The remainder showed a polarized pattern based on the type of leprosy. Lepromatous patients with disseminated disease had Th2-type cytokines, with IL-4 but not IFN-gamma. In contrast, tuberculoid leprosy patients with localized disease showed a Th1-like profile, with the presence of IFN-gamma but not IL-4. Of interest was the stability of the Th phenotype for M. leprae-related antigens. Both the recombinant and the peptide antigens induced the same phenotype as the natural M. leprae bacillus in all except four of 45 leprosy patients.

Antigens, Bacterial↗

Integration of leprosy control into basic health services; an example from Nepal.

The need for integration of vertical projects into the Basic Health Services (BHS) has been felt in Nepal since 1968. In 1987 it was decided to provide integrated BHS all over the country. The Nepal Leprosy Control Project (NLCP) was one of the vertical projects which had to be integrated from that year. In order to prepare the BHS staff for this new task the NLCP developed a Comprehensive Leprosy Training course. Besides adequate training, three other prerequisites for successful integration are: a) adequate supply of drugs and equipment; b) regular supervision and specialist referral facilities; and c) a well functioning BHS system in which to integrate. This article tries to assess to what extent these prerequisites have been met for leprosy control in Nepal. To do this, some results of an evaluation of the training are used as well as existing literature on the functioning of the BHS system. The first three prerequisites are not fully met, but problems and obstacles related to these are mainly due to problems in the last prerequisite: a not so well functioning BHS system. It was, therefore, recommended to continue a (semi)vertical support system of leprosy control in those districts where the BHS is not so well developed.

Health Personnel↗

Variants of HLA-DR2/DR51 group haplotypes and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians.

This study reports our observations on the correlation between HLA-DR2 subtypes and their DR-DQ haplotypes in patients with tuberculoid (TT) leprosy and pulmonary tuberculosis (PTB). DRB1*1501 was significantly increased in patients with PTB (90%) as compared to controls (p < 0.05); whereas the prevalence of DRB1*1502 was significantly increased in patients with TT leprosy (p < 0.05), suggesting allele-specific binding of the pathogen to form disease-causing motifs to the T-cell receptor. Among DR2-DQ haplotypes, the deviation was noted in the distribution of unique and common haplotypes in patients with TT leprosy and PTB. A significant decrease of haplotype DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0502 in TT leprosy and a significant increase of DRB1*1501-DRB5*0101-DQA1*0103-DQB1*0601 in PTB patients were observed. The occurrence of specific DR2 subtypes and their haplotypes in the two disease groups suggests their involvement in disease pathogenesis.

Adult↗

Early diagnosis and treatment of leprosy in the United States.

Leprosy is a chronic disease of the skin and peripheral nerves that afflicts more than 5 million persons worldwide and more than 7,000 persons in the United States. Although leprosy is indigenous to the southern United States, most new cases in this country occur among immigrants from foreign areas where the disease is endemic. Leprosy presents as a skin rash and/or peripheral neuropathy. The diagnosis can be confirmed when acid-fast bacilli are found in skin biopsies or smears. The multiple-drug treatment regimens recommended by the World Health Organization have considerably reduced the length of treatment to six months to two years. The optimum duration of treatment has yet to be determined. In most countries, including the United States, leprosy remains one of the most stigmatizing diseases.

Diagnosis, Differential↗

Application of polymerase chain reaction for the detection of Mycobacterium leprae DNA in specimens from treated leprosy patients.

In this study of leprosy patients apparently cured by dapsone monotherapy, the polymerase chain reaction (PCR), one of the most reliable and sensitive DNA-based assays, was used for the specific detection of Mycobacterium leprae DNA. Sputum and slit-skin samples from 44 such patients at Baba Baghi Leprosy Sanatorium in Iran were examined. Primers for a 530-base-pair fragment of the gene encoding the 36-kDa antigen of M. leprae were used for the study. The PCR results were compared with microscopy for acid-fast bacilli. Of the 44 sputum samples, 2 were positive by PCR (4.5%) and of the 44 slit-skin swabs taken from the same patients, 10 were PCR positive (22.7%). Only one patient was PCR positive for both sputum and slit-skin specimens (2.3%). No positive results were found by acid-fast microscopy. In total, 11 of 44 (25%) patients in this study were found to be PCR positive for M. leprae, and it was thought probable that this indicated the presence of live organisms. Particularly interesting was the statistically significant association of positive results from slit-skin swabs with paucibacillary rather than multibacillary leprosy. It is suggested that whereas relapse or immunological reaction in paucibacillary disease may result from surviving organisms, in multibacillary leprosy this may be due to re-infection.

Adult↗

Inter-observer variability in the assessment of nerve function in leprosy patients in Ethiopia.

One of the major problems in leprosy is to detect any change in nerve function early enough so as to increase the chances of recovery and prevent disability. Several tests have been developed to assess nerve function and are used in leprosy control programs worldwide, but they are frequently performed by different workers on different occasions and under variable conditions. In this study we investigated the variability between different groups of observers in the assessment of nerve function in leprosy patients in Ethiopia. Sensory function was assessed by using a set of nylon monofilaments (NF) and a ball-point pen (BP), and motor function was assessed by using voluntary motor testing (VMT). We also studied the variability between observers in the assessment of the clinical signs of neuritis. Duplicate measurements were performed in random order on 50 leprosy patients by two physio-technicians and on 50 other patients by two health assistants. The percent agreement between observers was calculated for each single nerve, and weighted kappa statistics were used to assess whether agreement was better than expected due to chance alone. Systematic differences between observers were evaluated using the Wilcoxon signed rank test. On sensory testing, inter-observer variability was found to be related to the training and experience of the observer, to the nerve tested, and to the neurological status of the patient. When tests were performed by physio-technicians, we observed 32% to 58% agreement with the NF test and 71% to 84% agreement with the BP test, measured on different scales. After weighting for the scale difference, the agreement seemed comparable with these methods but the differences in measurements with the BP test were found to be dependent upon the neurological status of the patient. The variability between observers differed according to the nerve tested, and there was some evidence of systematic differences between observers with both methods. When performed by the health assistants, agreement was between 34% and 46% with the NF and between 66% and 82% with the BP tests. After weighting for the scale difference, the agreement seemed comparable but the BP was not liable to the systematic differences seen in the NF results. These differences could be attributed to the differences in the experience of the workers with these tests. With the VMT, small variability between observers was found for all nerves tested, except the facial nerve, when performed by both the physio-technicians and by the health assistants (72% to 98% agreement).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Ocular histopathological studies in leprosy in the silent stage--II. Immunohistochemical studies].

The distribution of leprosy antigen in 21 eyes from 12 autopsy cases of lepromatous leprosy patients (5 eyes from 3 cases in the silent stage, 16 cases from 9 cases in the active stage) were examined with acid-fast staining and immunohistochemistry. Anti-BCG antibody, anti-phenolic glycolipid-I (PGL-I) antibody, and anti-lipoarabinomannan-B (LAM-B) antibody were used as primary antigens. In the active stage, anti-BCG antibody and anti-LAM-B antibody showed almost the same staining pattern. Some cases, which showed negative reaction to acid-fast staining, occasionally showed positive staining pattern with anti-BCG antibody and anti-LAM-B antibody, which had high sensitivity and the advantage of detection of leprosy antigen. Some anti-PGL-I antibody showed a different staining pattern from acid-fast staining, anti-BCG antibody and anti-LAM-B antibody. These findings seemed to be caused by the difference in structure of the epitope. In the silent stage, clinically nonpigmented epithelium of 6 cases from 4 eyes showed positive staining pattern with anti-PGL-I antibody. These findings suggested that leprosy antigen still remained in this stage.

Aged↗

Professional freedom of government leprosy personnel.

BACKGROUND: Government employment in India is known for its lack of flexibility. We studied whether this also involved professional freedom among health personnel working for the National Leprosy Eradication Programme. METHODS: The sample population consisted of National Leprosy Eradication Programme employees from Tamil Nadu and Andhra Pradesh and 8 health professional groups. A questionnaire was developed for each of them to elicit information on 5 aspects of their autonomy. They were studied individually and as homogeneous groups so that comparisons were possible both within and between groups in different regions who were conducting similar health programmes. RESULTS: National Leprosy Eradication Programme personnel enjoy a high degree of autonomy within the organization. This autonomy was evident in both states investigated, despite different administrations and it was not connected with the professional positions they held. Professional freedom correlated with the training activities, promotional prospects and commitment to the organization. CONCLUSIONS: The National Leprosy Eradication Programme job is not rigid because the organization is small and the intellectual needs of the professionals are met within it.

Adult↗

Defective leukotaxis in patients with lepromatous leprosy.

Serums from patients with lepromatous leprosy show a high incidence of a chemotactic inhibitor. This inhibitor acts directly on leukotactic factors (bacterial chemotactic factor, C3 fragment, and C5 fragment) to render the factors irreversibly inactive. Functionally, the inhibitor acts as a chemotactic factor inactivator. While normal serum shows no inhibitory activity under the conditions employed, inhibitory activity causing more than 30 per cent reduction of the bacterial chemotactic factor was found in the serums from 14 of 19 patients with lepromatous leprosy. Although exceptions were noted, a correlation was found between the presence of the inhibitor and depressed skin reactivity to a series of antigens (Lepromin, Trichophytin, Candida, PPD, and mumps antigen) used for elicitation of delayed-type hypersensitivity reactions. The presence in leprosy serums of this inhibitor may be responsible, at least in part, for some of the defects of cellular inflammatory responses in patients with lepromatous leprosy.

Chemotaxis↗

Ocular findings in leprosy patients in Nigeria.

An ophthalmic assessment of patients in four out of the five leprosy clinics in Anambra State, eastern Nigeria, showed that 63% had ocular disease and 43.5% had sight-threatening disorders. Most of the problems occurred in multibacillary leprosy patients. The blindness rate of (8.7%) is nearly 10 times higher than that within the general population in area. The causes of blindness were cataract, exposure keratopathy and uveitis. Some patients also had glaucoma and chorioretinal lesions. Eye health service within the leprosy control service in the area is non-existent. The importance of giving priority to blindness prevention in leprosy patients in the area is emphasised.

Adolescent↗

The 20th Kellersberger Memorial Lecture, 1994. Leprosy and tuberculosis combined programmes: an uneasy partnership?

One of the purposes of this memorial lecture is to relate progress and difficulties in the field of leprosy to work in other fields. Tuberculosis is a disease closely related to leprosy and in 1982 the Kellersberger lecture was given by Dr. Styblo, someone whose name is synonymous with the development of effective Tuberculosis Control Programme in Africa. His title was "Tuberculosis and its control: lessons to be learned from past experience, and implications for leprosy control programme" (1). Many countries in Africa, including Ethiopia, have adopted the strategy of a combined leprosy and TB control programme. In this lecture then, I will examine more closely the strategy of combining the two programmes. I want to look at some of the problems that may arise and then draw out the ways in which each side of the partnership can contribute to the other, so that the combination can be more effective than either programme could hope to be on its own. This lecture will focus mainly on management issues, which are currently the most important barriers to effective control of both diseases, but the socio-economic aspects of disease, so much a part of Dr. Kellersberger's working life, will also be prominent.

Cost-Benefit Analysis↗

Immunoglobulin-bearing cells in leprosy.

Peripheral blood lymphocytes of 28 untreated and 17 treated patients with different types of leprosy were investigated for the occurrence of immunoglobulin (Ig) bearing cells by means of a smear method. Seven healthy Africans served as controls. In a later stage a complementary study was performed on 6 tuberculoid and 6 lepromatous leprosy patients by means of a suspension method. The immunofluorescence technique was used for the detection of Ig-bearing cells, In tuberculoid leprosy an increase of Ig-bearing cells seems to occur during treatment, predominantly expressed by an increase in IgD-bearing cells. In lepromatous leprosy no increased percentages of Ig-bearing cells were observed.

B-Lymphocytes↗