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An epidemiological study of leprosy disability in a leprosy endemic rural population of Pondicherry (south India).

The disability rate in this study was 16.23%. The highest disability rate of 30.76% was found in those aged 45 years and above. Disabilities were found to be more common among male leprosy patients with a disability rate of 21.05% compared to that of 11.45% found among female leprosy patients. None of the indeterminate leprosy patients showed any disabilities, whereas all the neuritic and lepromatous leprosy cases showed disabilities. The disability rate among tuberculoid leprosy patients and borderline leprosy patients were found to be 3.25% and 35% respectively. Persons whose monthly per capita income was less than Rs. 200/- constituted 93.50% of the cases with disabilities. Anaesthesia of the hand was seen in 67.4% of the cases. The mean disability index (DI-2 type) was 0.927.

Adolescent↗

Leprosy type 1 reaction as the first manifestation of borderline lepromatous leprosy in a young native German.

While leprosy is usually a chronic disease, leprosy reactions may lead to acute problems. These reactions most often occur after initiation of therapy, but can also develop before treatment. Leprosy rarely presents with a reaction. We describe a German patient who presented in this unusual way in order to demonstrate the various tools used to confirm the diagnosis. A young German woman suddenly developed progressive functional loss of the left hand and within a few weeks an increasing number of erythematous macules and nodules appeared. Histological examination of a skin biopsy revealed tuberculoid granulomas, some located around small nerves; acid-fast bacilli were detected microscopically and DNA from Mycobacterium leprae was identified by polymerase chain reaction in the biopsy and a nasal swab; serological tests were positive. The disease was classified as borderline lepromatous leprosy. The acute neuritis followed by skin lesions represented a leprosy type 1 reaction in which the immune system reacts to bacilli previously unrecognized in nerve tissue, both in nerve and skin.

Acute Disease↗

Use of a whole blood assay to evaluate in vitro T cell responses to new leprosy skin test antigens in leprosy patients and healthy subjects.

Development of an immunological tool to detect infection with Mycobacterium leprae would greatly benefit leprosy control programmes, as demonstrated by the contribution of the tuberculin test to tuberculosis control. In a new approach to develop a 'tuberculin-like' reagent for use in leprosy, two new fractions of M. leprae depleted of cross-reactive and immunomodulatory lipids- MLSA-LAM (cytosol-derived) and MLCwA (cell wall-derived)-have been produced in a form suitable for use as skin test reagents. T cell responses (interferon-gamma (IFN-gamma) and lymphoproliferation) to these two new fractions were evaluated in a leprosy-endemic area of Nepal using a simple in vitro whole blood test. The two fractions were shown to be highly potent T cell antigens in subjects exposed to M. leprae-paucibacillary leprosy patients and household contacts. Responses to the fractions decreased towards the lepromatous pole of leprosy. Endemic control subjects also showed high responses to the fractions, indicating high exposure to M. leprae, or cross-reactive mycobacterial antigens, in this Nepali population. The new fractions, depleted of lipids and lipoarabinomannan (LAM) gave enhanced responses compared with a standard M. leprae sonicate. The cell wall fraction appeared a more potent antigen than the cytosol fraction, which may be due to the predominance of the 65-kD GroEL antigen in the cell wall. The whole blood assay proved a robust field tool and a useful way of evaluating such reagents prior to clinical trials.

Adult↗

IgA and IgM antibodies against Mycobacterium leprae in cord sera and in patients with leprosy: an indicator of intrauterine infection in leprosy.

A solid-phase radioimmunoassay was developed for demonstration and quantification of IgA and IgM anti-M. leprae antibodies. IgA and IgM anti-M. leprae antibodies were demonstrated in a lepromatous serum pool, in various amounts in individual patients with lepromatous leprosy, and in lower concentration in tuberculoid leprosy and non-leprosy controls. IgA and IgM anti-M. leprae antibodies were demonstrated in cord sera from babies of mothers with leprosy. The reliability of fetal IgA and IgM antibody synthesis as an indicator of intrauterine infection in leprosy is discussed.

Antibodies, Bacterial↗

Leprosy. XII. T-cell subsets in lepromatous leprosy.

The authors quantitated T-rosette-forming cell (TRFC) and T-cell subsets (T mu, T gamma) in the peripheral blood of twenty patients with lepromatous leprosy. The results obtained in their studies are as follows: (1) They reconfirmed the low levels of TRFC in patients with lepromatous type of leprosy; (2) T-cell subsets, both T mu (helper) and T gamma (suppressor) cells, showed lower levels in all patients with lepromatous leprosy than mean values of normal healthy controls; (3) The degree of decreased levels of T mu cells (96%) was more severe than other parameters TRFC (70%) and T gamma cells (47%) in all patients with lepromatous leprosy; and (4) It may be concluded that the alteration of the T-cell subset, T mu-cells, reflects a more fundamental abnormality than TRFC aberration in demonstrating the impairment of cell-mediated immunity in patients with lepromatous leprosy.

Adolescent↗

Concurrent skin and nerve histology in leprosy and its role in the classification of leprosy.

Concurrent skin and nerve histology was evaluated in 60 leprosy patients (25 BT, 28 BL and 7 LL). The twin aims were to study the comparative histology and the usefulness of nerve histology in the classification of the disease. In BT patients, clinical and histological classification was in agreement in 11 (44%) skin and 17 (68%) nerve biopsies. Concurrent skin and nerve histology was in consonance in 14 (56%) BT patients, while in 6 (24%) patients, only nerve histology was helpful in the classification of the disease, the skin histology being non-specific. Nerve histology was classified as BL in 3 (12%) BT patients, the skin histology was non-specific. In the BL group, the histology of 23 (82.4%) nerve biopsies correlated with the clinical classification, in contrast to skin histology which correlated with clinical assessment in 19 (68%) patients only. In the LL patients, the histology of nerve correlated with the clinical classification in 5 patients (71.4%), compared to histology of the skin in 4 (57%) patients only. The GF was higher in the nerves than in the skin throughout the leprosy spectrum (BT, BL, LL); the difference was, however, marginal in BL leprosy. The average bacteriological index (BI) was higher in nerves (4+) compared to that of skin histology and slit skin smears (3+) in BL leprosy. There was, however, no difference in the BI of the slit skin smears, skin and nerve biopsies in lepromatous leprosy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Nerve function impairment in leprosy: design, methodology, and intake status of a prospective cohort study of 2664 new leprosy cases in Bangladesh (The Bangladesh Acute Nerve Damage Study).

The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study designed to investigate epidemiological, diagnostic, therapeutic and operational aspects of acute nerve function impairment in leprosy. The study is based at a single centre in Bangladesh, in an area with a high prevalence of leprosy. The centre, Danish Bangladesh Leprosy Mission, has a well-established vertical leprosy control programme. In this paper, the study design and methodology are described, together with definitions of nerve function impairment (NFI) used in this and subsequent papers. The study recruited 2664 new leprosy cases in a 12-month period. The male:female ratio is 1.25:1, and 17.61% of the cohort are under 15 years of age. In all, 83.33% of the cohort are paucibacillary (PB), and 16.67% multibacillary (MB). However, the MB rate amongst males is 19.72%, and amongst females is 12.85%, despite an equal period of delay to diagnosis. 55% of patients presented for treatment within 12 months of developing symptoms 6.12% of the total number of cases were smear positive, and 36.71% of the MB cases were smear positive. 9.61% of the total number of cases were graded as having World Health Organisation (WHO) disability grade 1, and 5.97% had grade 2. Amongst MB cases, 27.48% had WHO grade 1 disability present, and 18.24% had grade 2 present, compared with 6.04% and 3.51%, respectively, amongst PB cases. A total of 11.90% of the cohort had sensory NFI of any kind, and 7.39% had motor NFI. Ninety patients presented with NFI needing treatment (3.38%), and of these, 61 (67.78%) had silent NFI. MB patients had a prevalence of reaction/NFI needing treatment nearly 7 times higher than PB cases (15.32% amongst MB; 2.30% amongst PB), and males nearly double that of females (5.67% amongst males, 2.96% amongst females). The most commonly affected nerve by function impairment was the posterior tibial (sensory) with 6.46% of nerves affected (9.38% of patients), followed by the ulnar nerve with 3.23% of nerves impaired (5.56% of patients). Future research and publications, building on this foundation, will focus on the following areas: the incidence of NFI and reactive events, the risk factors for developing NFI, and the response to treatment of patients developing acute NFI.

Bangladesh↗

Leprosy affected beggars as a hidden source for transmission of leprosy.

BACKGROUND & OBJECTIVES: Despite the large scale implementation of multidrug therapy (MDT), the incidence rates of leprosy have not declined in several hyperendemic countries. Before searching for non-human reservoirs of leprosy it would be necessary to look for hidden human sources. This would include destitute leprosy affected persons who resort to begging and operate in congested areas. Hence this study was undertaken. METHODS: One major town and three semi-urban areas in Vellore district of Tamil Nadu and Chittoor town in Andhra Pradesh were purposefully selected for the study. All beggars in these towns were systematically identified and examined by allopathic doctors. Skin smears were examined for bacteriological index. RESULTS: Among the 193 beggars screened, 58 had leprosy. Of these 10 were smear positive. Several beggars, although living separately, were in touch with their relatives. Most beggars were pavement dwellers and regularly begged at places of worship, bus stands and shopping centres. INTERPRETATION & CONCLUSION: The fact that nearly 20 per cent of the leprosy affected beggars were skin smear positive highlights the need for regular screening and treatment of such beggars. Those positive should be actively treated and their close contacts frequently screened. This hidden reservoir should be completely eliminated.

Adolescent↗

Biochemical, immunological and genetic studies in leprosy. I. Changes in serum lactate dehydrogenase isoenzymes, creatine phosphokinase and aldolase activity in different forms of leprosy.

Serum lactate dehydrogenase isoenzymes, creatine phosphokinase and aldolase activity were determined in healthy control subjects and in lepromatous and tuberculoid leprosy patients from Ethiopia. Sera from lepromatous patients showed a higher total LDH activity compared with control subject. The values for tuberculoid leprosy patients were similar to those of controls. Sera from normal healthy controls showed a higher proportion of LDH-H form (72%) while lepromatous leprosy patient's sera exhibited a higher proportion of LDH-M form (55%). Tuberculoid leprosy patients showed a pattern similar to that of healthy controls. A possible significance of these observations is discussed. No significant variations were observed in fructose-1,6-diphosphate aldolase activity within the different types of disease and controls. Although creatine phosphokinase levels in different types of leprosy decreased significantly from those of normal healthy, it falls within the reported variation of the activity in normal sera.

Creatine Kinase↗

Type 1 reactions in leprosy--heterogeneity in T-cell functions related to the background leprosy type.

Nineteen each of paucibacillary borderline tuberculoid (BT) and multibacillary borderline borderline (BB)/borderline lepromatous (BL) leprosy patients undergoing type 1 reactions were compared with nonreactional stable patients of the appropriate leprosy type. In the BT reactional group, both phytohemagglutinin-induced and, more importantly, antigen-induced lymphoproliferation was reduced in 80%-90% of the patients. On the other hand, leukocyte migration inhibition was reduced in 40% and remained unchanged in the others. Suppressor-cell activity as evaluated by a costimulant assay was also reduced in a majority of the reactional BT individuals. In contrast, the bacilliferous BB and BL patients in reaction showed significant general improvement in leukocyte migration inhibition (p less than 0.001) and antigen-induced lymphoproliferation (p less than 0.05) as compared to the expected hyporesponsive/anergic uncomplicated BB-BL patients. Suppressor-cell activity also recovered during the reactional phase. However, no significant differences were observed in either of the reactional or stable leprosy types in the numbers of total T cells (OKT3+) and their subsets as defined by OKT4+ (helper/inducer) and OKT8+ (suppressor/cytotoxic) functional phenotypes. Moreover, during type 1 reactions the 48-hr delayed-type hypersensitivity (DTH) responses after intradermal injection of Mycobacterium leprae antigens continued to reflect the background leprosy type rather than the functional perturbations in the circulating T cells. Only a marginal increase in DTH was observed in some BT reactional individuals. No consistent pattern in the above in vitro T-cell-related responses was discernable in the same individuals 4-6 months after subsidence of reactions. The clinical entity of type 1 reactions encompassing paucibacillary and multibacillary leprosy shows a heterogeneity/dichotomy in T-cell responses which may reflect different immunological mechanisms underlying the reactional state.

Antigens, Bacterial↗

Immunological problems in leprosy research. 1. Clinical and pathological spectrum of leprosy.

This paper discusses the evidence for and against the view that the spectrum of pathological changes in leprosy, extending from the lepromatous form to the tuberculoid form, may be caused by differences in the immune responses of patients. Patients with the tuberculoid form of leprosy generally have well-developed specific cell-mediated immunity, but in a large proportion of patients with lepromatous leprosy the specific cell-mediated immunity to Mycobacterium leprae and sometimes to other antigens seems to be deficient, whereas the circulating antibody response is well-developed. Techniques for assessing the immune response in patients are described in detail with the objective of improving the comparability of such investigations. The paper also discusses the importance of several investigatory approaches to clinical leprosy and the value of animal models for leprosy research.

Animals↗

Knowledge about leprosy among leprosy patients.

A study on "Knowledge of Leprosy in Leprosy patients" was conducted in the Dermatology outpatient department of JIPMER. The study has shown that a good percentage of leprosy patients possess proper knowledge of leprosy in respect of its awareness, nature of treatment, consequences of lack of treatment and prevention of disease. Knowledge regarding the cause and mode of spread of disease and duration of treatment was lacking in majority of patients These areas should be given more concentration in educating the leprosy patients. It was found that literate patients possessed better knowledge than illiterate patients.

Adolescent↗

Antibody response to recombinant 65-kDa, 70-kDa and 18-kDa mycobacterial antigens in leprosy patients and healthy contacts in a leprosy-endemic population.

Antibody responses to recombinant Mycobacterium leprae 65-kDa (rML65) and 18-kDa (rML18), M. bovis BCG 65-kDa (rMB65) and M. tuberculosis 70-kDa (rMT70) antigens were measured by indirect ELISA in sera from leprosy patients and healthy contacts in a leprosy-endemic area in southern India. Antibody responses to M. leprae-specific epitopes on phenolic glycolipid-I (PGL-I) and a 35-kDa protein antigens also were measured simultaneously by PGL-I ELISA and the serum antibody competition test (SACT), respectively. Significantly higher levels of antibodies of the IgG isotype to rML65 and rMB65 were observed in bacterial index (BI)-positive, lepromatous (LBI+) patients but not in other groups of leprosy patients and endemic controls [healthy family contacts (HFC), healthy hospital contacts (HHC), and healthy non-contacts (HNC)]. LBI+ patients could be distinguished from LBI- patients on the basis of their higher levels of IgG antibodies to rML65, rMB65 and rMT70; lower levels of IgM antibodies to these antigens and higher levels of anti-PGL-I IgM levels. In the former group, 84% were SACT positive in contrast to 39% in the latter groups. Among lepromatous patients good positive correlations were observed between IgG antibody responses to rML65 and rMB65 and anti-PGL-I IgM levels, SACT ID50 titers as well as BIs. Among healthy controls, HFC had higher levels of IgG antibodies to rML65, but lower levels to rMB65 than did HNC. Thirty-nine percent of the HFC were seropositive to anti-PGL-I IgM antibodies in contrast to 4% in the HNC. On the basis of these criteria, the immune profile of the HFC appears to be distinctly different from that of the HNC, even though both groups are from the same endemic area. It is therefore possible that antibody response to defined protein antigens of mycobacteria is influenced by the lesional bacterial load in leprosy patients and by exposure to homologous proteins of M. leprae and/or related environmental mycobacteria in the case of healthy contacts and noncontacts. The above results are discussed in relation to T- and B-cell activity toward M. leprae antigens and the immunoregulatory mechanisms of antibody production in leprosy.

Antibodies, Bacterial↗

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

AIM: This paper is the first in a series of three reports on the occurrence of reactions and impairments in leprosy in Thailand. This first paper gives a general overview about the methodology of the study, some epidemiological observations, delay in detection, multidrug therapy (MDT) completion rates and relapses. The other two papers report on: II. Reactions and III. Neural and Other Impairments. This study was carried out from 1987 until 1995 in three neighboring provinces in northeastern Thailand. STUDY DESIGN: A population-based, prospective cohort study. STUDY POPULATION: All 640 newly diagnosed leprosy patients in the three provinces, registered between October 1987 and September 1990, were included [420 paucibacillary (PB) and 220 multibacillary (MB)]. This group was followed up (actively and passively) until the end of 1995. METHODS: Patients were found by active and passive case finding. All new, untreated leprosy patients from the area were enrolled and started on the World Health Organization (WHO) MDT (WHO/MDT) regimen. A vertical control service was run by specialized leprosy workers. During treatment the patients received their monthly doses at home. During surveillance the patients were followed up once a year by a special team. Patients were questioned about delay in detection. Treatment completion rates were calculated. The occurrence of reactions and neural and other impairments at the beginning of, during and after treatment was ascertained. After treatment, the occurrence of late reactions and relapses was recorded. RESULTS: A higher frequency of leprosy was found among the male patients, especially in the MB group. However, in the PB group a higher female/male ratio was found in the age group 55 years and older. There was an increase in the detection rate from the youngest age group to the age group 55 years and older, which showed the highest detection rate. Treatment completion rates were high, 95% in both in the PB and MB treatment groups. About 50% of the new cases reported a delay between onset and registration of 1 year or more. By 1995, 93% of the original patient group was still available for follow up. By the end of 1995, 8 PB and 2 MB relapses were recorded.

Adolescent↗

The effect of leprosy management on leprosy complications at Alupe Hospital, Busia, Kenya.

A retrospective study of leprosy complications among new cases recruited for multiple drug therapy (MDT) at Alupe Leprosy Hospital between January 1986 and January 1992 was carried out to determine their prevalence, incidence and their relationship with disease classification. Out of 154 cases studied majority fell in the Borderline tuberculoid (BT) class (47%). The total follow up period was 186 person years giving an overall incidence rate of reactions of 20 per 100 person years. Overall point prevalence of complications for both males and females were highest in the extremities and ranged between 10% and 46% while the overall period prevalence ranged between 14% and 73% per year. There was a significant number of incident cases of complications during the follow-up period and comparison of different complications with different disease classes had odds ratios of around unity showing that MDT alone as an intervention measure plays no significant role in onset or progress of leprosy complications. It is observed that Borderline tuberculoid (BT) and Borderline lepromatous (BL) leprosy patients are at the highest risk of developing leprosy complications.

Journal Article↗

Ophthalmic findings of newly diagnosed leprosy patients in Istanbul Leprosy Hospital, Turkey.

The objective of this study was to detect ocular lesions of newly diagnosed leprosy cases admitted to Istanbul Leprosy Hospital. The patients were categorized according to sex, age, type of leprosy and duration of the disease. Their eyes were categorized as with or without ocular findings due to leprosy. The total number of patients was 21. The mean age was 22+/-4.6 years, the duration of the disease was 36.3+/-19.6 months. Madarosis was the most common finding in this group. It was found in 15 patients (71.4%, 95% confidence interval (CI) 47.8-88.7%). As a second common finding related to corneal alterations, 13 patients had nerve thickening (61.9%, 95% CI 38.4-81.8%). None of our patients had trichiasis, episcleritis, scleritis, cataract, iris atrophy, iris pearl, abnormal vitreous or retinal findings.

Adolescent↗

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↗