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Effects of risedronate on lumbar bone mineral density, bone resorption, and incidence of vertebral fracture in elderly male patients with leprosy.

There is no well-established treatment for osteoporosis in male patients with leprosy, because no clinical trials have examined the efficacy of treatment on bone mineral density (BMD) or fracture incidence in such patients. The purpose of the present study was to evaluate the therapeutic effect on oral administration of risedronate in male osteoporotic patients with leprosy. Twenty-three male patients with leprosy, 63-87 years of age, were randomly divided into two administration groups: R group (risedronate, 2.5 mg/day, daily) and P group (placebo, daily). The BMD of the lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry, and urinary cross linked N-telopeptides of type I collagen (NTX) were assessed at baseline, 6 months, and 12 months after treatment. There were no significant differences in age, body mass index, BMD, or urinary NTX levels at baseline between the two groups. In the present study, oral administration of risedronate apparently prevented vertebral fractures by increasing lumbar BMD and caused a significant reduction in urinary NTX levels, while oral administration of placebo did not increase the lumbar BMD and prevent vertebral fractures due to osteoporosis. The above findings suggested that oral administration of risedronate contributed to the prevention of vertebral fractures by suppressing bone resorption and increasing in lumbar BMD in the elderly male patients with leprosy.

Aged↗

Trends in new case-detection leprosy in Bihar, India.

Multi-drug therapy (MDT) has been successfully implemented in all leprosy endemic countries. Prevalence of leprosy has declined remarkably after the introduction of MDT. Detection of new cases did not show expected decline in many endemic and low endemic situations. Bihar in India started implementing MDT in 1993. The Damien Foundation India Trust (DFIT) supported the leprosy control programme in Bihar by providing a district technical support team (DTST) for each district assigned to DFIT. Effective coverage was achieved in 1996-98. Data for the period 1996-2004 from 10 districts are presented in this paper. The total population in these districts was 29.4 million. Deformity among newly detected leprosy patients declined to 1% indicating effective early case-detection. Intensive new case-detection activities were in vogue contributing to high new case-detection rate (NCDR). The NCDR remained high during the 9-year period reported here and did not show any declining trend.

Drug Therapy, Combination↗

Mycobacterium leprae-specific T cells from a tuberculoid leprosy patient suppress HLA-DR3-restricted T cell responses to an immunodominant epitope on 65-kDa hsp of mycobacteria.

The polar tuberculoid type (TT) of leprosy, characterized by high T cell reactivity to Mycobacterium leprae, is associated with HLA-DR3. Surprisingly, DR3-restricted low T cell responsiveness to M. leprae was found in HLA-DR3-positive TT leprosy patients. This low responsiveness was specifically induced by M. leprae but not by M. tuberculosis and was seen only in patients and not in healthy controls. We studied this patient-specific, M. leprae-induced, DR3-restricted low T cell responsiveness in depth in one representative HLA-DR3-positive TT leprosy patient by using T cell clones. From this patient two types of T cell clones were obtained: one type was cross-reactive with M. tuberculosis and recognized an immunodominant epitope (amino acids 3 to 13) on the 65-kDa heat shock protein (hsp) the other type was M. leprae specific and reacted to a protein other than the 65-kDa one. To examine whether these M. leprae-specific T cell clones were responsible for the DR3-restricted low responsiveness to M. leprae, we tested them for the ability to suppress the proliferation of the DR3-restricted, 65-kDa, hsp-reactive clones. The DR3-restricted, M. leprae-specific T cells completely suppressed the proliferative responses of DR3-restricted, cross-reactive T cell clones to the 65-kDa hsp from the same patient as well as from other individuals. Also, DR3-restricted responses to an irrelevant Ag were suppressed by the M. leprae-specific T cell clones. However, no suppression of non-DR3-restricted T cell responses was seen. Although the mechanism must still be elucidated, this M. leprae-induced, DR3-restricted immunosuppression may at least partly explain the observed DR3-associated low T cell responsiveness in TT leprosy patients.

Bacterial Proteins↗

Inter-state variations in integration of leprosy services into general health system in low/ moderately endemic states of India.

The objective of the study was to analyse inter-state variations in integration of leprosy services into the general health system, covering broad categories of structure integration, training of health functionaries, availability of MDT services and record maintenance, in 24 low/moderately endemic states. Multi-stage random sampling technique was used to select 9 states, 86 health facilities (including district hospitals, community health centres, primary health centres) and 108 sub-centres. Information from each level was collected on a pre-tested form by officers of three leprosy institutions of the Government of India. The results showed wide inter-state variations on each aspect. Redeployment of vertical staff was complete (100%) in Tamil Nadu and Tripura. Assam reported a higher level of training (97%) of medical officers in leprosy. Training of health supervisors and multipurpose workers was better than that of medical officers in most of the states. Tripura reported negligible training of all the health functionaries because of specific local problems. In Assam, Maharashtra and Sikkim, all the urban and rural health facilities were providing MDT. Three months' stock of all types of MDT blister packs was available only in one health facility in Andhra Pradesh and in Goa. Assam and Haryana had lower availability of MDT stocks. In Assam and Maharashtra, medical officers in all health facilities were diagnosing and treating leprosy cases, as compared with Himachal Pradesh where the value was 30%. Involvement of sub-centres in MDT delivery was more at 92% and 100% in Tamil Nadu and Maharashtra respectively in comparison to none in Himachal Pradesh and Tripura. Use of the Simplified Information System (SIS) 2002 guidelines and formats was universal. However, lower involvement of GHS staff in recording and reporting was noted in Assam (0%), Andhra Pradesh (10% and 30%). The study emphasized the need for further tailor-made follow-up studies to suit local problems.

Delivery of Health Care, Integrated↗

Affection of immune zones in leprosy: a clinico-epidemiological study.

The study was undertaken to evaluate the prevalence of involvement of immune zones in leprosy and to assess the clinico-epidemiological characteristics of the disease in patients presenting with immune zone involvement. 200 leprosy cases were included in this study and detailed history, clinical examination, slit-skin smears and skin biopsies were carried out on all patients. Those cases presenting with immune zone involvement were further evaluated for clinical and epidemiological characteristics of disease process. Immune zone involvement was detected in 7% of cases with male preponderance in the study. Majority of patients (85.5%) had borderline tuberculoid leprosy and midline of back was the commonest site of involvement (50% of cases). Morphologically, macular lesions were the commonest presentation (85.68%) of immune zone involvement. The study heightens the clinical awareness of the possibility of occurrence of leprous lesions on uncommon and unusual sites, which should be termed as relatively immune, rather than absolutely immune zones of leprosy.

Adolescent↗

Problems and needs of women leprosy patients in Bombay and Goa--a preliminary report.

By studying the status of 151 women leprosy patients (24 from a leprosy asylum and 127 attending urban leprosy centres at Goa and Bombay), it was noticed that a sizeable proportion experienced problems in society ascribable to the disease especially at the initial stages of the disease. However, most of them seemed to have managed to settle well in their families as housewives subsequently. Younger women leprosy patients expressed the need for financial assistance for completing their own education and for starting small scale business. The older women were more interested in educating their children.

Adolescent↗

Use of the anti-PGL-I antibody ELISA and the Mitsuda reaction in early diagnosis of leprosy.

Cutaneous reaction to the Mitsuda antigen and anti-PGL-I IgM antibodies (ELISA) were determined in 134 leprosy patients, 290 household contacts, 52 healthy controls and 43 tuberculous individuals. The multibacillary patients did not develop cell-mediated immunity (CMI), although they presented high levels of IgM (absorbance at 492 nm greater than 0.5). The paucibacillary patients presented CMI, although in varying degrees, and IgM levels did not exceed 0.5 absorbance units. Most of the contacts (107) showed a Mitsuda-positive test, and 25 of them were anti-PGL-I IgM seropositive (absorbance less than 0.5 but greater than 0.22), although none became ill during the two-year follow-up. Of the 17 Mitsuda-negative contacts, two exhibited an immunological status of lepromatous leprosy (negative Mitsuda test and positive serology; absorbance greater than 0.5) and became ill (one borderline lepromatous and one indeterminate leprosy). These results show that the immunological status of lepromatous leprosy can appear prior to clinical symptoms, and thus serology for anti-PGL-I IgM together with the Mitsuda test can be useful in an active search for new preclinical cases among high risk populations.

Antibodies, Bacterial↗

[Perspectives on fighting leprosy].

This review presents current distribution of leprosy in the world. The immunologic analyses of the histopathology and pathogenesis of the various stages of leprosy is discussed. The present effectiveness of multidrug therapy (MDT) in the face of emerging resistance to anti-leprosy drugs is presented as well as different attempts for preparing safe and effective vaccine against leprosy.

Global Health↗

Immuno-epidemiological studies on subclinical infection in leprosy. III. Yearly observations and follow-up studies of schoolchildren by using FLA-ABS and lepromin tests.

The schoolchildren in three regions of Miyako Islands, Okinawa Prefecture, were surveyed annually, from 1978 to 1984, by using the fluorescent leprosy antibody absorption (FLA-ABS) test and the lepromin reaction with the Dharmendra's antigen, for detecting the individuals at high risk of leprosy and for evaluating predictive value of these immunological tests. Constant potency of these tests was confirmed by the percentage of positive reactions among the children in the first grade of elementary schools (5 or 6 years old) surveyed from 1980 to 1984. A temporal rise or drop of the percentages during this period seemed to associate with the yearly reported number of new leprosy cases in each region. Among 1,168 schoolchildren tested with FLA-ABS once or twice or more, the percentage of positive reactions was significantly higher in the children with the enlargement of peripheral nerve without sensory loss than in those without this signs and symptoms. The longer the duration of this signs and symptoms, the higher the percentage of positive FLA-ABS tests. Lepromin test did not show any significant correlation with this signs and symptoms. A concordant persistence or change between the FLA-ABS tests and neural signs or symptoms was observed in 133 out of 331 children examined twice or more. Discordant changes in the remaining were mainly attributed to a conversion to seronegativity before the disappearance of neural signs and symptoms. Changes of FLA-ABS and lepromin reactivities between the initial and final tests suggested a spontaneous cure of subclinical infection with Mycobacterium leprae among the children who were FLA-ABS positive but lepromin negative at the initial test and therefore considered to be a group at high risk of leprosy. Although neural signs and symptoms were found in the majority of these children, none of them so far developed overt symptom of the disease. Based on these findings, predictive value of FLA-ABS test together with lepromin was discussed.

Age Factors↗

Effect of glucocorticoids and interferon-gamma on the oxidative responses of monocytes from leprosy patients and normal donors.

Leprosy patients suffering from erythema nodosum leprosum are frequently treated with glucocorticosteroids. The role glucocorticosteroids and interferon-gamma (IFN-gamma) play in regulating the interaction of phagocytic cells with Mycobacterium leprae was examined. Monocytes from leprosy patients receiving prednisone therapy responded to lower concentrations of IFN-gamma in vitro with enhanced superoxide anion release when challenged with M. leprae or M. bovis BCG than did monocytes from healthy subjects and other leprosy patients. Although the number of patients was small and the population heterogeneous, the data suggested that prednisone could alter IFN-gamma efficacy and led to the examination of the effect of glucocorticosteroids on IFN-gamma activation of monocytes. IFN-gamma treatment following in vitro dexamethasone pretreatment of monocytes from healthy subjects resulted in a greater enhancement of superoxide anion generation than that observed with IFN-gamma treatment alone. These findings are important considerations in evaluating patient immune function because IFN-gamma is being used in a number of clinical trials with leprosy patients.

Adult↗

A serologic study of naturally acquired leprosy in chimpanzees.

Data from longitudinally obtained serum samples spanning several years has permitted us to identify two chimpanzees with leprosy and to estimate the time of Mycobacterium leprae exposure/infection. The results confirm high levels of specific anti-M. leprae phenolic glycolipid-I (PGL-I) as well as anti-lipo-arabinomannan (anti-LAM) antibodies in both chimpanzees, and identify additional chimpanzees with possible M. leprae exposure. The observations are consistent with the hypothesis that leprosy exists in chimpanzees in the U.S.A. and suggest the possibility that M. leprae may be transmitted among chimpanzees. The data suggest that monitoring anti-PGL-I and anti-LAM IgG and IgM levels longitudinally in leprosy contacts may be useful in the recognition of preclinical leprosy.

Animals↗

Expression of a common idiotype PR4 in the sera of patients with leprosy.

The sera of 187 patients from across the leprosy spectrum were screened for the expression of the PR4 idiotype, which was first identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy and found to react with the Mycobacterium leprae phenolic glycolipid and a variety of polynucleotides. Sixty per cent (51 out of 85) of patients with lepromatous leprosy (LL), 66% (33 out of 49) with borderline lepromatous (BL) disease, 47% (14 out of 30) with borderline tuberculoid (BT) leprosy, and 56% (13 out of 23) of tuberculoid (TT) patients were found to have significantly elevated titres of the PR4 idiotype in their sera compared with endemic controls, irrespective of the presence or absence of endemic malaria. Sera from 52 patients with tuberculosis were also screened as a control for mycobacterial infection. The PR4 idiotype was significantly elevated in 37% (19 out of 52) of these patients. No correlation between idiotype and serum immunoglobulins IgG and IgM was found, indicating that the concentrations of idiotype levels in sera were not merely a reflection of changes in serum immunoglobulin levels. It is hypothesized that the expression of the PR4 idiotype is due to certain germline genes preferentially expressed rather than being the result of polyclonal B cell activation.

Animals↗

Leprosy in the WHO African region.

The African Region has the second largest prevalence of leprosy among the WHO regions with about 1 per 1,000 population affected. With a very uneven distribution among countries, the region currently has a total of about 480,000 registered cases. The number of new cases detected per year is reported to be about 37,000. A high proportion (25-40%) of the registered cases are estimated to have significant physical disabilities. In spite of the introduction of multidrug therapy (MDT) in the early 1980s, currently only about 20% of the patients are benefiting from this improved treatment. The major problem in the low MDT coverage appears to be operational, against the background of a difficult socioeconomic situation. However, there have been favourable trends towards increased political commitment in several countries in recent years. The operational and technical constraints were discussed at an interregional conference in Brazzaville in 1989 which emphasized the need to make use of the opportunities to reduce disease prevalence through MDT; to coordinate various internal and external resources available for leprosy control; to increase political commitment and develop plans of action to build national capabilities for leprosy control; to integrate leprosy control within general health services; and to promote health education.

Africa↗

Global review of multidrug therapy (MDT) in leprosy.

Leprosy continues to be an important public health problem in most countries of Asia, Africa and Latin America. While there has been a steady increase in the number of registered leprosy cases from 1966 to 1985, since then there has been a substantial reduction of over 30% in the number of registered cases. This is mainly attributed to the introduction of multidrug therapy (MDT) as recommended by a WHO study group on chemotherapy of leprosy for control programmes in 1981. The coverage for MDT has steadily increased over the last 5 years, reaching a global figure of 55.7% of all registered cases by October 1990. Over 2 million leprosy patients are currently undergoing MDT and, in addition, over 1 million patients have completed MDT since 1985. MDT has been found to be generally well tolerated with a high level of acceptability leading to improved treatment compliance. MDT coverage shows wide variations among WHO regions and among individual countries. The prospects for further reductions in prevalence of registered cases in the next decade are very bright. However, problems such as early case detection, and prevention and management of disabilities after patients have been curred for several years, will continue to pose significant challenges.

Africa↗

[Endemic leprosy in the People's Republic of Congo. An epidemiological and behavioral analysis].

The authors report the results of a national prevalence survey of leprosy made in 1989 in Popular Republic of Congo. Leprosy is essentially found in rural areas and frequently causes disabilities. The prevalence rate is 5.8 +/- 2.6% among people more than 15 years of age, and 10.5% of all forms are multibacillary. All patients are under DDS monotherapy. One overwhelming risk factor is leprosy cases in the family history; active case-finding and surveillance of contact cases are recommended. Generally, leprosy is poorly understood by the general population; an educational effort is necessary.

Adolescent↗

A quantitative study of the relationship between systemic and histological parameters of immunity in individual leprosy patients.

A group of 52 untreated leprosy patients were examined to determine the relationship between local and systemic immunological parameters across the clinico-pathological spectrum. The Ridley-Jopling classification, bacterial index (BI), and granuloma fraction (GF) were assessed in biopsies from 40 cases. The densities of apoptoses, mitoses, and plasma cells were also measured. Systemic immunity to mycobacteria was assessed by skin tests with leprosin A and PPD, and by measurement of the serum antibody responses to Mycobacterium leprae, M. tuberculosis, and M. scrofulaceum. The serum responses to phenolic glycolipid-I (PGL-I) of M. leprae was assessed using a glycoconjugate which mimics an immunodominant epitope. The serum antibody levels and skin test results showed the expected inverse relationship. The BI within lesions showed an inverse correlation with the skin test results, but none of the other histological parameters studied showed a significant relationship with the other measurements of systemic immunity. Our findings suggest that the inverse relationship between delayed-type hypersensitivity and humoral immunity in leprosy patients, which is strong in groups of patients across the leprosy spectrum, is less strong in individual patients than is often thought. The lack of correlation of many histological and systemic parameters suggests that local factors modulate systemic immunity in the pathogenesis of leprosy lesions.

Adolescent↗

[A case of autochthonous leprosy (author's transl)].

A case is reported of autochthonous leprosy in a French patient who had never lived in an endemic zone. The disease was of the lepromatous leprosy type and the liver, spleen, skin nerves and muscles were affected. Characteristic findings were Hansen's bacillus in nasal scrapings, a deficiency in cellular immunity, and the presence of cryoglobulins and circulating immune complexes. Autochthonous leprosy which has not been imported, and without signs of direct contagion, appears to be exceptionally rare. The authors review the clinical forms of leprosy and immunological findings.

Humans↗

[Preliminary study on leprosy subclinical infection and its sero-epidemiology].

The detection of subclinical infection with M. leprae among 360 household contacts of leprosy and 95 healthy controls was conducted with PGI-ELISA in leprosy-endemic areas. The relationship of age at infection, and onset with epidemic trends was explored basing on the distribution features of subclinical infection with M. leprae in household contacts of leprosy. In addition, the multiple linear regression was used to analyse the factors affected the level of antibody in leprosy.

Adolescent↗