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PubMed1995

[The protective efficacy of BCG against leprosy in São Paulo, Brazil].

The protection against leprosy conferred by BCG vaccination was evaluated in a case-control study. Selected for the study were 97 patients under 16 years of age who had been diagnosed with leprosy (cases) and 385 healthy persons (controls), who were matched according to sex, age, place of residence, and type of contact (intra- or extradomicilliary). The cases were selected from a register of active cases as well as a series of new leprosy patients treated in 50 centers in the city of São Paulo, Brasil. To estimate the protective effect of BCG, the prevalences of BCG scars among cases and controls were compared. The presence of one or more scars was associated with a protective efficacy of 90% (95% confidence interval: 78%-96%). Stratified analysis by age group, sex, socioeconomic level, and clinical form of leprosy did not reveal any important differences in the protection conferred by the vaccine. The significance of these findings and the appropriateness of using BCG in leprosy control programs is discussed.

Adolescent↗
PubMed1995

Prevention of impairment in leprosy; results from a collaborative project in China.

OBJECTIVE: to evaluate programs of prevention and treatment of impairments due to leprosy in 8 geographical areas in the People's Republic of China. DESIGN: follow up of cohorts of leprosy patients receiving a range of different interventions. SETTING: 8 different geographical areas in China, varying in urban and rural characteristics from 6 provinces and 2 municipalities. SUBJECTS: leprosy patients who were receiving or had completed a course of antileprosy chemotherapy. INTERVENTIONS: a range of interventions, including steroids, self-care training, adapted footwear, surgery and provision of prostheses. MAIN OUTCOME MEASURES: changes in eye, hand and foot impairments between baseline assessment and assessment at 2 years. RESULTS: 232 out of 3571 patients assessed monthly over 2 years developed acute neuritis and, in most areas, were promptly and adequately treated. Regular self care of eyes was established in 238 out of 313 patients with lagophthalmos and was associated with reduction in the prevalence of conjunctivitis. Regular self care of hands was established in 730 out of 1010 patients with neurological impairment of the hand; this was associated with a reduction (80%) in hand cracks and wounds. Regular self care of feet was established in 745 out of 1094 patients with neurological impairment of the feet; this was associated with a 83% reduction in patients with cracks and a 33% reduction in patients with sole wounds. A footwear program was established in all 8 areas providing footwear to 4698 patients over the 2-year period; this was associated with a reduction of 61% and 21% in patients with cracks and wounds, respectively. Management of complicated sole wounds in 256 patients resulted in 69% of these patients being free of sole wounds at 2 years. Targets for reconstructive surgery and amputations were not fully attained, but lower limb prostheses were provided for 306 patients. CONCLUSIONS: leprosy is a chronic disease characterized by peripheral neuropathies which can result in increasing secondary impairments and disabilities. The emphasis, in countries such as China where the chemotherapy programs have been effectively implemented, is shifting to prevention and treatment of impairments. This innovative program in China has successfully demonstrated that it is possible to prevent and reverse impairments due to leprosy.

Artificial Limbs↗
PubMed1995

Use of facility-based assessment in the evaluation of a comprehensive leprosy training program in Nepal.

A facility-based assessment (FBA) was done to evaluate a comprehensive leprosy training program in Nepal. The training course was developed to prepare the Basic Health Services staff for integrated leprosy work. FBA is a coordinated set of data collection activities designed to determine the extent to which patients are properly diagnosed, treated, and cared for in the treatment facility. During the present evaluation, the data collection activities included: observation of health worker performance, exit interviews with leprosy patients, interviews with health workers, inventory of essential equipment and supplies, and collection of routine statistical data. The objectives of the training course were used as guidelines for the evaluation. Surveys and observation visits were done repeatedly and compared with a (untrained) control group. Different actors involved in leprosy care were used as informants, and different data collection methods were used which enabled cross-checking of the information. Part of the data collection activities was already routinely carried out. FBA proved to be a very useful and effective tool for the evaluation of a leprosy training program. Those parts of the training which need extra attention during the course itself as well as during refresher training and supervision visits became obvious.

Health Facilities↗
PubMed1995

Enhancement in the histological diagnosis of indeterminate leprosy by demonstration of mycobacterial antigens.

In a clinico-pathological study of Indeterminate leprosy, fifty-six cases were chosen based on specified clinical criteria. Their clinical features were noted, the smears for acid fast bacilli (AFB) were prepared from lesions, lepromin inoculation and biopsies were performed from the lesional edges. They were subsequently treated with a modified extended WHO regimen for paucibacillary leprosy. On routine hematoxylin eosin (HE) and Fite-Faraco staining of paraffin embedded sections, histopathological confirmation of Indeterminate leprosy was observed in only 17/56 (31%) of the clinically diagnosed cases whereas the remaining were labelled as non-specific pathology. Histometric analysis of all HE stained sections did not show any characteristic finding which could be considered as characteristic and discriminatory for Indeterminate leprosy. Immunoperoxidase staining for demonstration of mycobacterial antigen by direct staining procedure using conjugated rabbit anti-BCG and indirect three step procedure using primary rabbit anti-BCG and avidin biotin complex, was next performed on the sections exhibiting non-specific pathology. With the direct immunoperoxidase method, antigen was demonstrable in (11/35) 31% of the cases. The more sensitive indirect method could demonstrate the presence of antigen in (21/35) 60% of the cases. This study thus shows that demonstration of mycobacterial antigen by simple and inexpensive immunoperoxidase techniques enhances the histopathologic diagnosis of Indeterminate leprosy.

Adolescent↗
PubMed1996

Minocycline-induced hyperpigmentation in leprosy.

A 36-year-old man was treated with dapsone, rifampicin and clofazimine for borderline lepromatous leprosy. After 9 months, his leprosy plaques became progressively more red and after 23 months, the clofazimine was stopped and he was given minocycline instead. Six weeks later, he developed blue-black pigmentation in his leprosy lesions. The histology was consistent with minocycline-induced hyperpigmentation. This is the first report of minocycline-induced pigmentation in leprosy. We suggest it is important to consider this side-effect before the administration of minocycline in leprosy, particularly if it is prescribed in place of clofazimine.

Adult↗
PubMed1996

Protective efficacy of BCG against leprosy in São Paulo.

The case-control study reported here evaluated the protective effect of BCG vaccine against leprosy in São Paulo, Brazil. Seventy-eight patients under age 16 who had been diagnosed as having leprosy (cases) and 385 healthy individuals (controls) were selected and matched by sex, age, place of residence, and type of exposure to leprosy (intradomiciliary or extradomiciliary). The cases were drawn from an active patient registry and from a group of new leprosy cases treated at 50 health centers in the cities of Bauru and Ribeirão Preto in the state of São Paulo. In order to estimate the protective effect of BCG, the prevalences of BCG scars in cases and controls were compared. The presence of one or more scars was associated with an estimated protective efficacy of 90% (95% confidence interval: 78% to 96%). Stratified analysis by age group, sex, socioeconomic level, and clinical form of the disease revealed no significant differences in the protection provided by the vaccine. However, it seems clear that more data will be needed in order to accurately assess the true relevance of BCG for leprosy control programs.

Adolescent↗
PubMed1996

Stigma and socio-economic reintegration of leprosy sufferers in Nigeria.

Leprosy is the commonest cause of peripheral neuropathy in the world. This feature causes gross deformities of the face and limbs of infected individuals as well as crippling disabilities involving sight, touch and manual dexterity. Such stigmata intensified the social and economic isolation of patients. Although concerted efforts by national governments and international organisations have made leprosy cease to be a medical problem in most parts of the world, leprosy still remains a "human problem": about 30% of past or present leprosy sufferers in Nigeria are disabled and/or handicapped as a result of the disease. This paper reviews the various factors contributing to leprosy stigma in Nigeria and proposes ways of minimising it.

Attitude to Health↗
PubMed1996

[Anatomopathologic study of five cases of leprosy in HIV seropositive patients].

In an effort to establish whether the human immunodeficiency virus (HIV) modifies the histological image of lepromatous skin lesion, a comparative study was conducted in 1994 at the Marchoux Institute in Bamako, Mali, on persons newly suffering from leprosy who had been tested seropositive and seronegative for the HIV virus. These new leprosy patients had never been treated and could be grouped as follows: 5 HIV-positive (1 TT, 1 BT, 1 BL, 2 LL) and 10 controls testing HIV-negative, selected according to the following criteria: each seropositive leprosy subject was matched with two seronegative controls having the same clinical features, same stage under the Ridley classification system, same age and sex. No discordance between the clinical classifications and the histological features in the subjects testing HIV-positive has been observed. They display features similar to those testing negative, with the presence of histiocytes, in particular epithelioid cells and giant cells in normal proportion depending on the form of leprosy. The only remarkable difference was a greater incidence of oedema in the subjects testing seropositive, compared with patients testing seronegative. In conclusion, HIV infection does not appear to cause major modifications in cellular response to Mycobacterium leprae, and no changes should be made in leprosy control programmes.

AIDS-Related Opportunistic Infections↗
PubMed1977

Haematological profile in leprosy. Part I--general findings.

Haematological studies in 904 adult leprosy patients with different types of leprosy, in various stages of the disease and treatment are described. Haemoglobin, packed cell volume, serum albumin and serum iron are significantly lower among lepromatous leprosy patients as compared with non-lepromatous patients. The serum B12 levels were significantly higher among the lepromatous group. Acid fast bacilli have been demonstrated in skin smear negative leprosy patients with indeterminate and tuberculoid leprosy, suggesting occurrence of bacillaemia in these groups of patients.

Adult↗
PubMed1997

Trends in leprosy case detection rates.

BACKGROUND: A systematic review of the trends in leprosy incidence is lacking. The question of whether leprosy transmission has declined remains, therefore, unanswered. This study investigates trends in new case detection rates (NCDRs) in selected leprosy-endemic areas from different continents. METHODS: A literature search using specific inclusion criteria was performed. Average annual rates of change in NCDRs were obtained by exponential curve fitting. The variation in trends within individual areas was investigated using direct and indirect information on leprosy control activities. RESULTS: This review covers 16 areas in the Pacific, Asia, Africa and Latin America. For 10 out of the 16 areas, the trend was seen to be declining consistently over the last 10 years or longer. Near stabilization or stabilization after decline was observed for two areas. For three areas, interpretation of recent NCDRs was difficult due to changes in control, but two of them showed a decline over the study period. A consistently increasing trend was observed over the last 20 years in the one remaining area. The observed downward trends could not be attributed to reduced control activities or changed diagnostic criteria. A general acceleration of downward trends in the NCDR after the introduction of multidrug therapy (MDT) has not so far occurred. CONCLUSION: Our main conclusion is that despite many differences between the studies and study areas, the review demonstrates a considerable tendency of downward NCDR trends. Lack of information and changing control conditions necessitate caution in interpreting NCDR trends in individual areas. A general impact of MDT on NCDR trends is so far not visible. The coming years will be crucial for MDT-based control to prove its ability to reduce leprosy incidence.

Adult↗
PubMed1998

The nose in leprosy: immunohistology of the nasal mucosa.

A detailed study of the nose was undertaken in 40 leprosy patients with different classifications of leprosy and different durations of disease at two hospitals in Brazil. This manuscript describes the immunohistochemical data on cellular infiltrates in the nasal biopsies of those patients. It was surprising that the damage to the whole depth of the nasal mucosa, epithelium and lamina propria was considerable, as was the case in the nasal mucosa which looked relatively normal during clinical inspection. The epithelium showed large holes which looked like very extended goblet cells. Very obvious was the lack of vasoconstriction after cocaine application, and the vessels also showed a lack of staining with factor VIII, possibly indicating a disruption of the endothelium. The number of neurofilaments was extensively reduced in all leprosy groups compared to normal controls. As in the skin, an increased number of CD68+ cells was found in the lamina propria of the nasal mucosa of the lepromatous patients. Contrary to findings in the skin, in the nasal mucosa of the borderline/lepromatous patients the number of CD4+ cells was increased and the number of CD8+ cells was decreased compared to normal controls. The number of CD8+ cells tended to be more reduced when the history of leprosy was longer. It is not clear as yet whether the reduced numbers of CD8+ cells are acquired during infection or whether persons with a low number of CD8+ cells in the nose might have a higher risk of acquiring leprosy.

Adult↗
PubMed1997

Genetic variations at the T cell receptor gamma locus in circulating peripheral blood mononuclear cells of clinically categorised leprosy patients.

The allelic polymorphisms at exon 3 and exon 2 of the T cell receptor (TCR) C gamma 2 (TRGC2) gene, generating 18-kb and 5.4-kb HindIII fragments, respectively, were found to be more frequent in multibacillary leprosy patients than in the controls (P < 0.005 and P < 0.001, respectively) when screened with the IDP2.11 probe. The frequencies of heterozygotes for the 18-kb allele and homozygotes for the 5.4-kb allele were found to be significantly higher in the multibacillary patients than in the controls (P < 0.001). Interestingly, the 8.0-kb allele, originating from the triplication of exon 2 of C gamma 2, was observed exclusively in the paucibacillary leprosy patients. Further, when DNA samples were screened with the pH60 probe for the HindIII RFLP at the TCR J gamma 2 (TRGJ2) gene segment, the 2.1-kb allele was again more prevalent in leprosy patients with the multibacillary form of the disease than in the paucibacillary patients and the controls (P < 0.025). The frequency of homozygotes for the 2.1-kb allele was also significantly higher in the multibacillary patients than in the paucibacillary patients (P < 0.010) and the controls (P < 0.025). A significant difference was observed in the frequencies of detectable rearrangements involving the V gamma 7/8 and V gamma 9 gene segments at the gamma locus between circulating peripheral blood mononuclear cells of the multibacillary leprosy patients and the controls. These rearrangements were detected less frequently in the multibacillary patients (P < 0.001 for V gamma 7/8 and P < 0.005 for V gamma 9).

Alleles↗
PubMed1998

Study of ethmoid sinus involvement in multibacillary leprosy.

The nasal mucosal involvement in lepromatous leprosy is well recognized. Currently interest has centred around the involvement of paranasal sinuses in leprosy. They act as a reservoir and constant source of reinfection to the nasal mucosa. In the present prospective study 25 untreated patients with multi-bacillary leprosy were included. Clinical examination, computed tomography (CT) scan of paranasal sinuses, ethmoid sinus endoscopy and biopsy were carried out in all patients, to investigate the involvement of the paranasal sinuses in leprosy. Ethmoid sinus involvement was noted in 20 patients on CT scan. Bilateral involvement was more common (65 per cent). Anterior ethmoids were more commonly affected (65 per cent). On ethmoid sinus endoscopy abnormal mucosa was noted in 17 patients (68 per cent). Ethmoid sinus biopsy was confirmative in 16 patients (64 per cent). Statistically significant correlation was found between CT findings, sinus endoscopy and sinus biopsy findings.

Adolescent↗
PubMed2005

A recessive major gene controls the mitsuda reaction in a region endemic for leprosy.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The Mitsuda reaction is a delayed granulomatous skin reaction elicited by intradermal injection of heat-killed M. leprae. Interestingly, results of the Mitsuda test are positive in the majority of individuals, even in areas not endemic for M. leprae. Like leprosy, the Mitsuda reaction is thought to be genetically controlled, but its mode of inheritance is unknown, although the role of the NRAMP1 gene has previously been reported. METHODS: We conducted a segregation analysis of quantitative Mitsuda reactivity in 168 Vietnamese nuclear families ascertained through patients with leprosy. RESULTS: We found strong evidence (P<10-9) for a major gene controlling the Mitsuda reaction independently of leprosy clinical status. Subsequent linkage analysis showed that this major gene was distinct from NRAMP1. Under the major-gene model, approximately 12% of individuals are homozygous for the recessive predisposing allele and are predicted to display high levels of Mitsuda reactivity (mean, approximately 10 mm, versus 5 mm in other individuals). CONCLUSION: We provide evidence that the Mitsuda reaction is controlled by a major gene. Our study paves the way for the identification of this gene and should provide novel insight into the mechanisms involved in granuloma formation, especially in M. leprae infection.

Female↗
PubMed1999

Macular lesions in leprosy: a clinical, bacteriological and histopathological study.

Among 150 untreated patients of leprosy, 19 had only macular lesions; three were of the indeterminate type, and eight each were of the tuberculoid and the borderline types, according to the Indian Association of Leprologists (IAL, 1981) classification. The clinical, bacteriological, and histopathological parameters of these 19 patients were studied both before and after six months of WHO Multi Drug Therapy (MDT/1982). A single macule was present in seven (36.84%) patients. In twelve (63.16%), two or more were seen. In eighteen (94.74%), one or more peripheral nerves were enlarged. The size of the macules varied from 5 to 15 cm, and there were no changes seen even after treatment. In most (94.74%) of the patients, the macules were hypopigmented. The surfaces were rough and dry in seven (36.84%) but smooth in the other twelve (63.16%). The margins were well defined in the seven (36.84%) patients with single macules but ill defined in the other twelve (63.16%). After six months of antileprosy treatment, the single macules showed some resolution. Slit skin smear examination was negative in all cases before and after treatment. Clinico-histopathological correlations were seen in only six (31.58%) patients; the clinical diagnoses were indeterminate and tuberculoid leprosy in three (15.79%) patients each. In the indeterminate group, the clinico-histopathological correlation was 100%; it was 37.50% in the tuberculoid group. There were no correlations between the clinical and histopathological parameters in thirteen (68.42%) cases. After six months of treatment, the histopathology became nonspecific in all patients. The lepromin test was positive in six (31.58%) patients; four were of the tuberculoid group and one each from the indeterminate and borderline leprosy groups. Hence, although macular lesions can be seen throughout the leprosy spectrum, it is difficult to correlate their clinical, bacteriological and histopathological parameters.

Adolescent↗
PubMed1998

T-cell recognition of mycobacterial GroES peptides in Thai leprosy patients and contacts.

We report here the mapping of T-cell-stimulatory determinants of the GroES 10-kDa heat shock protein homologues from Mycobacterium leprae and Mycobacterium tuberculosis, which are known as major immunogens in mycobacterial infections. Peripheral blood mononuclear cells (PBMC) from treated tuberculoid leprosy or lepromatous leprosy patients and from healthy household or hospital staff contacts of the patients were cultured with 20 16-mer peptides covering the entire sequences of both M. leprae and M. tuberculosis GroES. The total number of recognized peptides was found to be the largest in family contacts, while responder frequencies to the individual tested peptides varied (5 to 80%) with specificity between the patient and contact groups. Proliferative responses to some peptides showed positive or negative associations of low statistical significance with DR and DQ alleles, though responses to most GroES peptides were genetically permissive. Notably, the sequence of the 25-40 peptide of M. leprae, but not that of M. tuberculosis, was more frequently stimulatory in tuberculoid leprosy patients than in either group of sensitized healthy contacts. This peptide bound to a number of HLA-DR molecules, of which HLA-DRB5*0101 had the strongest affinity. The epitope core binding to this allele was localized to the 29-to-37 sequence, and its key residue was localized to the M. leprae-specific glutamic acid at position 32. This epitope may be of interest for the development of a blood test- or skin test-based diagnostic reagent for tuberculoid leprosy, subject to further clinical evaluation in untreated patients.

Amino Acid Sequence↗
PubMed1990

Enzyme-linked immunosorbent assay for distinguishing serological responses of lepromatous and tuberculoid leprosies to the 29/33-kilodalton doublet and 64-kilodalton antigens of Mycobacterium tuberculosis.

Immunoblot assays for the antibodies to Mycobacterium tuberculosis sonic extracts showed that all serum specimens of 40 lepromatous and of 28 tuberculoid leprosy patients reacted in a significant manner to 29/33-kilodalton (kDa) doublet and 64-kDa antigens, respectively. By using an enzyme-linked immunosorbent assay, we observed a significantly high immunoglobulin G antibody titer to the purified M. tuberculosis 29/33-kDa doublet and 64-kDa antigens in lepromatous and tuberculoid leprosy patients, respectively, as compared with normal subjects and tuberculosis patients. This enzyme-linked immunosorbent assay serology may be useful for distinguishing two polar types of leprosy and for diagnosing leprosy in general.

Antibodies, Bacterial↗
PubMedDate not supplied

Cytomorphology of leprosy across the Ridley-Jopling spectrum.

OBJECTIVE: To evaluate the possible role of cytology in classifying leprosy lesions on the Ridley-Jopling scale. STUDY DESIGN: A double-blind, prospective study comparing cytologic assessment of 30 clinically diagnosed cases of leprosy with their histopathology. May-Grünwald-Giemsa and Ziehl-Neelsen stain were done on slit skin smears and fine needle aspiration material. RESULTS: Cytologic subclassification was possible in 23 cases as tuberculoid leprosy (11), midborderline (3), borderline lepromatous (5) and lepromatous leprosy (4). These correlated with histologic subtypes. CONCLUSION: May-Grünwald-Giemsa complements Ziehl-Neelsen stain, yielding information almost comparable to that from histologic examination of skin biopsies.

Biopsy↗