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Ultrastructural changes in blood vessels of peripheral nerves in leprosy neuropathy. I. Tuberculoid and borderline-tuberculoid leprosy patients.

Radial or superficial peroneal nerve biopsies of 6 patients with tuberculoid or borderline-tuberculoid leprosy and 6 control nerve biopsies were examined by electron microscopy. Endoneurial blood vessels showed histopathology in all the leprosy patients. Changes, in particular, involved the basement membrane in postcapillary venules and venules. Multilayered parellel basement membranes, with collagen and ground substance, formed a thick coat ("hyaline zone") around the vessels. It is suggested that the zone inhibits passage of nutrients and metabolites and, thus, contributes to or is the main cause of the local destruction of (unmyelinated) nerve fibres and the lack of nerve fibre regeneration observed in this type of leprosy. The perivascular zone, presumably, is produced by pericytes in response to defects in the "blood-nerve barrier" of endoneurial vessels. In granulomata of leprosy skin lesions, a perivascular zone was not present. The endothelium of endoneurial vessels, in affected nerves, generally was normal. Occasionally, however, gaps and fenestrations were seen and there were histological indications that leakage of blood plasma had occurred through the gaps and through the basement membrane of the endothelium. Occlusion of endoneurial vessels was found only in the oldest patient and the degeneration of nerve fibres generally observed thus is considered not to be caused by ischaemia. Histopathology in epi-and perineurial vessels was definitely less pronounced than in endoneurial vessels.

Adolescent↗

Vaccination against leprosy at Ben San Leprosy Centre, Ho Chi Minh City, Vietnam.

Three vaccines, BCG alone, BCG + 10(7) killed Mycobacterium vaccae and 10(8) killed M. vaccae alone, were studied in children living in close contact with leprosy. In the year before vaccination, 14/446 (3.1%) children had developed leprosy. Among those who were not vaccinated, 9/74 (12.2%) developed the disease in the first 4 years of the study and 5/65 (7.7%) developed the disease in the second 4 years. In comparison with this, among those vaccinated, 20/343 (5.8%) developed leprosy in the first 4 years and 5/323 (1.5%) developed leprosy in the second 4 years. This represents 52.5% protection in the first 4 years and 80.5% in the second 4 years. There were no significant differences in protection afforded by each of the three vaccines but the success of the killed preparation of M. vaccae is an important finding.

Adolescent↗

The immunology of leprosy: speculations on the leprosy spectrum.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The disease presents a wide spectrum of clinical manifestations, ranging from lepromatous to tuberculoid leprosy; each form may be punctuated by episodes of acute exacerbation, called reactional states. These polar forms and reactional states appear to be determined by immunologic interactions between the host and the microorganism. This review describes the different measurable parameters that permit the classification of a particular form according to clinical, bacteriologic, histologic, and immunologic spectra. Secondly, the current state of knowledge on essential immunologic features of leprosy is presented, with a description of the various alterations of cellular and humoral immune responses that can be tested by specific and nonspecific methods. The last part of the review is devoted to an analysis of the leprosy spectrum and to speculations about a number of possible factors that may influence the immune response of the host in a manner analogous to that observed in experimental models.

Animals↗

Cellular immune response to the cell walls of Mycobacterium leprae in leprosy patients and healthy subjects exposed to leprosy.

Cell walls of M. leprae consist of complex arrangements of carbohydrate, lipid, peptidoglycan and protein molecules. Recently, extractable proteins of a wide range of molecular weights were identified as components of the cell wall. We have examined the cellular immune responses of Nepali leprosy patients to a cell wall preparation of M. leprae enriched for these proteins. Strong lymphocyte proliferative responses to the antigens were present in half of the paucibacillary leprosy patients and in the majority of healthy control subjects with occupational exposure to leprosy. Patients with multibacillary disease responded poorly and patients with tuberculosis had intermediate responses. Proliferative responses to the cell wall protein fraction were strongly correlated to the proliferative responses to sonicates of the whole leprosy bacillus. Immunization of mice with cell wall proteins resulted in inhibition of growth of M. leprae following foot-pad inoculation with viable organisms. Therefore cell-mediated immune responses to the extractable proteins of the cell wall may play a role in protective immunity against M. leprae infection.

Adolescent↗

Is leprosy blindness avoidable? The effect of disease type, duration, and treatment on eye damage from leprosy in Uganda.

AIMS: The study was designed to measure the prevalence, range, and severity of eye involvement in leprosy patients; to relate this to disease type, duration, and treatment to identify risk factors; and to provide practical guidelines for programme managers and field staff on the prevention of blindness. METHODS: The visual outcome was assessed in a population based sample of patients in Kasese District, Uganda followed for up to two decades, and related to disease features and treatment. A total of 678 patients responded to an invitation out of 2715 registered since 1973. RESULTS: Low vision was present in 4.4% of people and blindness in 1.3%, with 1.5% and 0.6% respectively being due to leprosy. Some 12.4% of patients had iritis, of whom 33% had visual loss in one or both eyes, 3.7% of patients had lagophthalmos, and 11.7% had lens opacity. For multi-bacillary (PB) cases, the adjusted odds ratios were: for iritis 4.6 (95% CI 2.6-8.2), for lagophthalmos 1.4 (0.6-3.2), and for lens opacity 1.7 (1.0-3.0). Potentially sight threatening (PST) lesions were present in 16.8% of patients (95% CI 14.0-19.6). CONCLUSION: Levels of eye involvement in this study are low compared with many surveys. Visual loss is uncommon and is more often caused by other diseases; in the present era of multidrug therapy (MDT) it is very unlikely to be caused by leprosy. It is more common with advancing age. PST lesions, especially iritis, may occur in both PB and MB cases, even if the diagnosis of leprosy is made early and MDT started immediately; they may occur also after completion of MDT. But eye complications need not proceed to loss of sight if treated promptly, and blindness can be avoided. Training of front line staff is therefore crucial.

Adolescent↗

Measuring leprosy stigma--a preliminary review of the leprosy literature.

A literature review was conducted to review work done to date on measuring stigma related to leprosy. References were obtained through a PubMed (Medline) search and through examining relevant bibliographies. Twelve papers were selected that addressed the issue of measurement of stigma and that contained a sample of the instrument used. Three unpublished studies were also included in the review. Studies that attempt to measure stigma can be broadly categorized in two groups, a) studies that assess the effects of stigma on the person affected, and b) surveys that assess community attitudes and/or practices. The study and questionnaire characteristics of the studies in both categories are described and compared. The studies reviewed indicate that leprosy stigma is still a global phenomenon, occurring in both endemic and non-endemic countries. The consequences of stigma affect individuals as well as the effectiveness of leprosy control activities. Despite enormous cultural diversity, the areas of life affected are remarkably similar. They included mobility, interpersonal relationships, marriage, employment, leisure activities, and attendance at social and religious functions. This suggests that development of a standard stigma scale for leprosy may be possible. Data obtained with such an instrument would useful in situational analysis, advocacy work, monitoring and evaluation of interventions against stigma, and research to better understand stigma and its determinants.

Cross-Sectional Studies↗

[Social reproduction of leprosy: a study of patients profile with leprosy in the city of São Paulo].

This study discusses the relationship between work and living conditions among leprosy patients enrolled in the São Paulo municipal public health system in 1996. Social patterns were studied based on the theory of social determination of the health-disease process. The main purpose of the study was to emphasize evidence of the disease determination network, seeking new knowledge to improve public policies on leprosy. Data were gathered from a sample of leprosy patients registered in the city's public health system. Although patients' families are characterized by a common social thread, different work/life possibilities allow for a classification of patients into three social groups. The majority belong to groups that are marginalized from social production, living in areas where social exclusion is more extreme, on the outskirts of the city. If the trends in this study persist, incident leprosy cases will result from the social exclusion of migrants from Brazil's Southeast and Northeast. The study also discusses the position of young people and female patients in the determination network of this infectious disease in the city of São Paulo.

Adolescent↗

T lymphocyte reactivity of leprosy patients and healthy contacts from a leprosy-endemic population to delipidified cell components of Mycobacterium leprae.

In this study, we measured in vitro proliferative responses of peripheral blood mononuclear cells from both leprosy patients across the clinical spectrum and also healthy contacts from a leprosy-endemic population to delipidified cell components of Mycobacterium leprae (DCC) and Dharmendra lepromin. Dharmendra lepromin was poor in inducing in vitro T cell proliferation in all the study groups, even though it elicited marked in vivo skin test reaction in tuberculoid leprosy patients and healthy contacts. In contrast, Dharmendra preparation of BCG induced marked T-cell response in tuberculoid as well as bacterial index negative lepromatous patients. DCC induced a significantly higher lymphoproliferative response than Dharmendra lepromin in all study groups. A significant positive correlation was observed between the lymphoproliferative responses to DCC and BCG. The present study, based on a large number of leprosy patients and healthy contacts, clearly demonstrates that DCC, depleted of glycolipids and lipopolysaccharides, is a good antigenic preparation for evaluating T-cell reactivity to M. leprae.

Adolescent↗

The extent of leprosy-related disabilities in Istanbul Leprosy Hospital, Turkey.

This study was carried out between January and December 1992 at the Istanbul Leprosy Hospital. Seven hundred and eleven leprosy patients were evaluated according to their age, gender and type of disease and disability according to the WHO disability grading system (1980). There were 527 males (74.2%) and 184 females (25.8%) in the group. The average age was 50.0 +/- 13.5 years and the average duration of disease was 25.9 +/- 13.2 years. Six hundred and seventy-eight patients (95.4%) were in borderline (BL) and lepromatous (LL) leprosy. The extent of disabilities was very high in 711 leprosy patients. It was found that 539 of the patients (75.8%) had eye disabilities, 511 of them (71.8%) had hand disabilities, 521 of them (73.3%) had foot disabilities. The most frequent eye, hand and foot disabilities were a decrease of vision (52.7), acute or chronic iridocyclitis (48.8%), slightly-marked corneal sensory loss (43.2%), mobile claw hand (33.3%), palmar insensitivity (16.3%), plantar ulcer (37.2%) and plantar insensitivity (19.8%). Eye deformities were the most common of the three affected areas in this study.

Female↗

Multidrug therapy in multibacillary leprosy; experience in an urban leprosy center.

The article records the experience of treating multibacillary (BB, BL and LL) leprosy with multidrug therapy (MDT) in an urban leprosy center. The problem of leprosy is to be properly assessed throughout the Indian subcontinent because most of the epidemiological data from the areas labeled low-endemic have to be updated. The regularity of therapy must be ensured and monitored constantly, but in spite of our efforts to do so some factors were beyond our control, such as providing a means of livelihood for the migrants from other places. In addition, the intake of drugs also has to be periodically checked from the history and discoloration of skin and, most importantly, confirmed by performing random spot tests for dapsone in the urine. The main problems discussed are the difficulty in demonstrating acid-fast bacilli in slit-skin smears from the macular form of borderline leprosy (also called dimorphous macular) and, secondly, whether the duration of multibacillary therapy was adequate since only approximately 50% of our patients achieved smear negativity after taking MDT for the stipulated period of 24 months. Experiences from other centers have suggested that the duration of MDT should be prolonged in multibacillary patients to achieve smear-negative status. Yet another group notes that smear negativity is gradually achieved during the period of surveillance following stoppage of MDT after 24 months. These questions await more information from good centers with controlled field studies.

Dapsone↗

Leprosy and malignancy: autopsy findings of 252 leprosy patients.

The occurrence of malignant tumors in leprosy patients was studied in 252 autopsied cases. Malignant tumors were found in 33 out of 110 autopsy cases from 1962 to 1971, and in 51 out of 141 autopsy cases from 1977 to 1989 (until July). In 1974, a lepromatous case with Kaposi's sarcoma was autopsied. The incidence of malignant tumors in our 252 cases were 33.7% (85 out of 252). Carcinoma of the alimentary system was most common: stomach, liver and large intestine, in that order. There was an increased number of hepatocellular carcinoma closely related to liver cirrhosis. Carcinoma of the lung has increased remarkably in leprosy patients quite recently. Malignant lymphoma was the most common of the nonepithelial malignant tumors, and four of these cases were seen in lepromatous leprosy patients. Eight cases showed double or triple cancers; seven of these were autopsied during 1977 to 1989. Further studies should be done to ascertain which types of leprosy showed the highest incidence, and which sex showed more frequent malignant tumors.

Aged↗

Correlation between occurrence of leprosy and fossil fuels: role of fossil fuel bacteria in the origin and global epidemiology of leprosy.

On the basis of correlative data on the global distribution of leprosy, its bacteria metabolizing fossil fuels (FF), and the FF themselves, the origin of leprosy in the world as a whole, and in the leprosy-free countries, in particular, as indigenous cases, appeared to be primarily due to a soil-to-man, and secondarily due to a man-to-man infection. These findings helped to elucidate similar problems of animal leprosies and nocardial diseases.

Animals↗

Acid mucopolysaccharide metabolism in leprosy. 1. Storage of hyaluronic acid and its possible significance in the pathogenesis of leprosy.

A histochemical analysis of 102 skin biopsies from a variety of leprosy types revealed the persistent presence of hyaluronic acid in lepra cells of lepromas. In contrast, the hyaluronic acid content of tuberculoid epithelioid cells showed a minimum amount of hyaluronic acid and hyaluronic acid tended to disappear from these granulomas as they aged. The macrophages of dimorphous leprosy occupied an intermediate position with respect to hyaluronic acid content and distribution, resembling the tuberculoid in BT cases and the lepromatous expression in BL cases. It is suggested that hyaluronic acid, in a manner similar to M. leprae and lipid, has a quantitatively varied distribution reflecting the immunopathologic spectrum of leprosy. This finding suggests that acid mucopolysaccharide may be significantly involved in that host/parasite interaction in leprosy.

Adolescent↗

Prevalence of leprosy in children of leprosy parents.

A cross sectional clinical study was done in slums and adjoining village of Raipur town. All the children in 100 families, in which at least one patient of proved leprosy was present were examined. Children of 100 non-leprosy families served as control. In leprous families prevalence was 14.2 times higher in comparison to children in control group. Also prevalence was higher in children of those families in which number of patients were more than one, or there was lepromatous leprosy. In children the common type of lesion were tuberculoid, indeterminate, borderline and pure neural type in that order, while no case of lepromatous leprosy was seen.

Adult↗

Minerals in blood sera and scalp hair in patients with lepromatous leprosy and tuberculoid leprosy.

Scalp hair and blood sera of three groups of individuals were studied for mineral contents by flame photometric and colorimetric procedures. Patients in one of the three groups were suffering from lepromatous leprosy, the second group comprised patients with tuberculoid leprosy and the third group consisted of normal controls. The results obtained revealed changes in the mineral content of the scalp hair of those suffering from lepromatous leprosy and tuberculoid leprosy. A possible relationship may exist between hair and serum minerals.

Adult↗

The approach to the leprosy problem in the past in Indonesia. A historical review of leprosy control activities in Indonesia during the last centuries.

Due to the severe disabilities leprosy has always been a disease which appealed to the imagination. In bygone centuries cause and treatment were unknown and the fear to be infected was enormous. In Indonesia medical officers struggled with the problem. As early as the 17th century the disease was described in detail by Ten Rhijne. In the 19th century leprosy was considered hereditary. After the discovery of the leprosy bacillus by Hansen in 1873, confusion continued as the bacillus could not be cultivated. Many therapies were tried, but with no result. At first patients were isolated in leprosaria, later on a more humane system of house-isolation was introduced. Since 1932 Indonesian medical officers have played a prominent part in research and the determination of the future approach to the problem. Seen against the background of our present knowledge about the disease, it is interesting to follow the struggle against leprosy in the past.

History, 17th Century↗

Light and electron microscopic study of peripheral nerve damage in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL).

Cutaneous branches of radial nerves in patients with lepromatous leprosy (LL) and borderline lepromatous (BL) were studied by light and electron microscopy. Foamy macrophages were found more or less in the nerve fibers of all leprosy patients and distributed in the epineurial, perineurial and endoneurial areas. In the endoneurium, the foamy macrophages were mainly located in the subperineurial and perivascular spaces. Vacuolated Schwann cells were also found in the nerve fasciculus. In electron microscopy, these foamy macrophages and vacuolated Schwann cells contained numerous small dense materials, irregular in size and shape, considered to be degenerated and fragmented mycobacterium leprae. These dense materials were found also in the cytoplasm of vascular endothelial cells. These findings suggest that mycobacteria enter into the endoneurium via the blood vessels. In our present study, on the other hand, it was very difficult to find the intact mycobacteria in the cytoplasm of the foamy macrophages, Schwann cells or endothelial cells, as well as in the Ziehl-Neelsen staining of paraffin sections. The disappearance of intact bacilli in our present study might have been caused by multi drug therapy. The myelinated nerve fibers were degenerated and disappeared in variable degrees. Degenerative changes of the myelin sheath developed from the outer layer to the inner layer with disarrangement of the lamellar structure. These findings were different from myelin destruction of peripheral nerves in Wallerian degeneration. The degenerative changes of the myelin sheath are caused by degeneration and destruction of Schwann cells in leprosy patients. Fibrosis surrounding myelinated and unmyelinated nerve fibers, i.e., periaxonal fibrosis, was found to a greater or lesser extent in the endoneurium. In the present study, it is still unclear whether the periaxonal fibrosis was due to necrosis of the Schwann cells by infection of mycobacteria or to an autoimmune mechanism such as antiperipheral nerve antibody. However, lamellated concentric fibrosis surrounding regenerative myelinated and unmyelinated nerve fibers with the disappearance of mycobacteria suggests that degenerations and regenerations of nerve axons were repeated during clinical cause. These findings indicated that autoimmune mechanisms play an important role in the pathogenesis of periaxonal fibrosis.

Adolescent↗

Development of a whole blood assay to measure T cell responses to leprosy: a new tool for immuno-epidemiological field studies of leprosy immunity.

A whole blood assay is described to measure T cell mediated immune responses to leprosy and provide an alternative to the conventional lymphocyte transformation test. Optimal conditions were defined for the whole blood assay, and interferon-gamma measurement was found to be a more sensitive way of measuring responses than tritiated thymidine incorporation. The assay was shown to be useful for investigating responses to a range of leprosy antigens. A whole blood assay has the advantages of being quick, simple and requiring only a small volume of blood, making it more appropriate as an immuno-epidemiological field test in leprosy endemic areas.

Antigens, Bacterial↗