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Serum angiotensin-converting enzyme in leprosy and coccidioidomycosis.

Serum angiotensin-converting enzyme levels were found to be elevated in 71.4% of 42 leprosy patients, both treated and untreated, but in only one of 13 patients with disseminated coccidioidomycosis. The elevations with leprosy were present in association with each of the three major categories: lepromatous, borderline, or tuberculoid. Sulfone therapy had no immediate effect on the elevated serum levels, although long-term sulfone therapy appeared to result in lowering of the level. Corticosteroid therapy had a more immediate and dramatic effect on reducing the elevated angiotensin-converting enzyme level in leprosy. This assay cannot distinguish between sarcoidosis and leprosy or between the various categories of leprosy, but it can help differentiate sarcoidosis from fungal or tuberculous disease. Elevated levels of serum angiotensin-converting enzyme have now been associated with three diseases states: sarcoidosis, Gaucher's disease, and leprosy.

Coccidioidomycosis↗

LDH isozymes with anomalous bands in semen of leprosy patients.

Activity of LDH isozymes was evaluated electrophoretically on 7% acrylamide gel in semen of 37 leprosy patients (15 with borderline, 12 with borderline tuberculoid and ten with lepromatous leprosy) and ten fertile men of 30-45 years of age. Significantly lower activities were recorded of LDH1 in all categories of leprosy patients. Similarly, lowering of LDH2 activity was noticed in borderline and lepromatous cases only, lowering of LDH4 activity in lepromatous cases only and LDH5 activity was lowered in borderline leprosy patients. Lowest activity of LDH3 and absence of LDHx were found in lepromatous leprosy. However, in borderline tuberculoid patients, LDH3 and LDHx were significantly higher. This exceptional increase in activity was found to be due to presence of additional (anomalous) isozymes bands of LDH3, LDHx and LDH4 in 25% of borderline tuberculoid patients. Additional bands of LDH3 have also been located in 40% of the borderline leprosy patients.

Adult↗

Integration of leprosy control work with general health services as planned in Maharashtra.

The current literature on integration of Leprosy Control work with General Health Services has been reviewed. In view of the introduction of Multipurpose Workers' Scheme and an experience in a pilot project, the authors feel that the time of integration of leprosy is ripe. The process of involvement of Multipurpose Workers in the Leprosy Control Programme is being introduced in a manner that ensures adequate supervision by the present Leprosy Control staff during the training period and also subsequently for one year so that the transition from unipurpose to integrated service, is a smooth one. After the successful integration of leprosy, the leprosy staff, after adequate training, can be used as Multipurpose Supervisors.

Health Services Administration↗

Childhood leprosy--study of prevalence rates and clinical aspects through surveys in Bombay.

This paper summarises the experience gained through extensive surveys of school children carried out in Greater Bombay over the past five years. The strikingly high proportion of children of 6 to 14 years age group suffering from leprosy attending the Acworth Leprosy Hospital and its peripheral clinic prompted these surveys. While surveys of 10% of child population attending randomly selected municipal schools revealed a general prevalence rate of 3 per 1000, there existed pockets of endemicity of the order of 10.8 per 1000, in some schools situated in the northern suburbs of the city. Even private schools catering to the not-so-poor sections of the community showed prevalence rates of over 6 per 1000, confirming the hyperendemicity of leprosy in Bombay city, with no socioeconomic or age group immune from exposure. Clinical observations of 1265 leprosy cases identified in the course of the above surveys covering a total population of nearly 1.8 lakhs of school children are presented. 24.7% of the cases had either the potential to develop into progressive forms of leprosy in view of the multiplicity of lesions or were already in an advanced stage of the disease. Polyneuritic leprosy together with intermediate and lepromatous types representing 5.8% of all cases (24 cases were confirmed to be smear positive) belonged to the groups posing therapeutic as well as public health problems. Analysis of 953 cases with single lesions revealed greater frequency of distribution (58.4%) of patches in parts of the body which are generally covered. It is striking that 26.4% of the solitary lesions was found in the gluteal regions and thighs, emphasising the need for thorough examinations of these parts during surveys.

Adolescent↗

Anti-neutrophil cytoplasmic antibodies (ANCA) in the clinical forms of leprosy.

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies against enzymes present in primary granules of neutrophils and lysosomes of monocytes detected in systemic vasculitis and in other diseases, including infections. ANCA are markers of active Wegener granulomatosis, which presents some anatomo-pathologic and immune response features similar to those of leprosy. Thus, we raised the hypothesis that ANCA may be present in leprosy as markers specifically linked to the presence of vasculitis. The aim of this study was to determine the presence of ANCA in leprosy and its correlation with the clinical forms of the disease. Sera from 60 normal individuals and from 59 patients with different clinical forms of leprosy were studied. The patients were also allocated into reactional and nonreactional groups. By indirect immunofluorescence, ANCA were positive, an atypical pattern (A-ANCA), in 28.8% of the patient sera. A-ANCA predominated, although not significantly (p > 0.05), in the reactional groups 37.9% vs 20.0%), and in those at the lepromatous pole (41.6% vs 20.0%). There was no correlation between ANCA positivity and either disease duration, disease activity, or therapeutic regimen (p > 0.05). An interesting finding was the correlation between ANCA and gender: 94.1% of ANCA-positive patients were males (p < 0.01), a feature that so far has not been reported in ANCA-related diseases and for which there is no explanation at the moment. By ELISA, the sera of the lepromatous leprosy patients did not show activity against either PR3, MPO, HLE, the most common ANCA antigens. Because A-ANCA are nonspecific, this finding requires further investigation for the determination of the responsible antigen(s). In conclusion, A-ANCA are present in 28.8% of leprosy patients but are not related to vasculitis in the erythema nodosum leprosum reaction and are not a marker of a specific clinical form.

Adolescent↗

Social aspects and rehabilitation. International Leprosy Congress, Beijing, 7-12 September 1998. Workshop report.

1. Equal rights and opportunities for people affected with leprosy to develop their full potentials is a matter of human rights. 2. Leprosy and its consequences are a complex human problem leading to discriminations, stigma and prejudices. 3. There is lack of complete understanding about global needs for rehabilitation. 4. Concentration on medical care of people affected with leprosy (MDT, surgery, etc.), though vastly beneficial, has led to highly inadequate psycho-socio-economic rehabilitation in a holistic manner resulting in poor quality of life. 5. People affected with leprosy have not been full partners and decision makers for their own development and lack self-confidence and opportunities for self-expression. 6. Community and health providers lack the right attitude and sensitivity, thus failing to assist in the empowerment of people affected with leprosy in an integrated manner. 8. There is insufficient coordination at international/NGOs/government levels to utilize scarce resources to allow full development of people affected with leprosy.

Adaptation, Psychological↗

SIMLEP: a simulation model for leprosy transmission and control.

SIMLEP is a computer program for modeling the transmission and control of leprosy which can be used to project epidemiologic trends over time, producing output on indicators such as prevalence, incidence and case-detection rates of leprosy. In SIMLEP, health states have been defined that represent immunologic conditions and stages of leprosy infection and disease. Three types of interventions are incorporated: vaccination, case detection and chemotherapy treatment. Uncertainties about leprosy have led to a flexible design in which the user chooses which of many aspects should be included in the model. These aspects include natural immunity, asymptomatic infection, type distribution of new cases, delay between onset of disease and start of chemotherapy, and mechanisms for leprosy transmission. An example run illustrates input and output of the program. The output produced by SIMLEP can be readily compared with observed data, which allows for validation studies. The support that SIMLEP can give to health policy research and actual decision making will depend upon the extent of validation that has been achieved. SIMLEP can be used to improve the understanding of observed leprosy trends, for example, in relation to early detection campaigns and the use of multidrug therapy, by exploring which combinations of assumptions can explain these trends. In addition, SIMLEP allows for scenario analysis in which the effects of control strategies combining different interventions can be simulated and evaluated.

BCG Vaccine↗

Comparison of two methods of leprosy case finding in the circle of Kita in Mali.

Kita is a health district of Mali, a leprosy-endemic country in West Africa. We conducted a comparative study of passive and active case finding of leprosy in this district in 1997. In May and June, a mobile team realized active case finding by visiting 32 villages of more than 1000 inhabitants. For 12 months, peripheral health center nurses did passive detection after information and education sessions about the signs of leprosy in the other 37 main villages of Kita. The active detection rate (4.31 per 10,000) was threefold higher than the passive rate (1.5 per 10,000) and allowed us to find earlier cases of leprosy. Active case finding identified children and single-lesion disease; the passive method did not. Cost for finding a new case was estimated at 72 US$ by mobile team detection and 36 US$ by passive case finding. Although the active method looked more expensive than the passive one, it was the only effective strategy to detect leprosy patients in remote and difficult-to-access areas. Based upon the results of the study, a flow chart is proposed for the choice of case-finding method when designing a leprosy elimination program.

Cost-Benefit Analysis↗

Human leukocyte antigens in forms of leprosy among Japanese patients.

Human leukocyte antigens (HLA) class II alleles were analyzed among Japanese leprosy patients to ascertain whether immunogenetic differences exist among the leprosy classification forms of Ridley and Jopling. Ninety-three unrelated Japanese leprosy patients (21 lepromatous, 24 borderline lepromatous, 17 mid-borderline, 26 borderline tuberculoid, 5 tuberculoid) and 114 healthy control subjects were investigated. The frequencies of HLA-DRB1*1501, -DRB5*0101, -DQA1*0102 and DQB1*0602 were significantly increased in all of the Japanese leprosy patients. The frequencies of HLA-DRB1*0405, -DQA1*03 and -DQB1*0401 were significantly decreased in the Japanese patients after correction of the p value. Conversely, there were no significantly different distributions of the HLA-DRB1, -DRB5, -DQA1, DQB1 alleles in the five subgroups of these patients. We conclude that HLA class II alleles were not associated with the form of leprosy. Other HLA, a non-HLA gene, and/or environmental factors may play a critical role in the different manifestations of leprosy.

Cytotoxicity Tests, Immunologic↗

Mechanics of tarsal disintegration and plantar ulcers in leprosy by stress analysis in three dimensional foot models.

This paper describes three dimensional two arch models of feet of a normal subject and two leprosy subjects, one in the early stage and the other in the advanced stage of tarsal disintegration, used for analysis of skeletal and plantar soft tissue stresses by finite element technique using NISA software package. The model considered the foot geometry (obtained from X-rays), foot bone, cartilages, ligaments, important muscle forces and sole soft tissue. The stress analysis is carried out for the foot models simulating quasi-static walking phases of heel-strike, mid-stance and push-off. The analysis of the normal foot model shows that highest stresses occur at push-off over the dorsal central part of lateral and medial metatarsals and dorsal junction of calcaneus and cuboid and neck of talus. The skeletal stresses, in early state leprosy with muscle paralysis and in the advanced stage of tarsal distintegration (TD), are higher than those for the normal foot model, by 24% to 65% and 30% to 400%, respectively. The vertical stresses in the soft tissue at the foot-ground interface match well with experimentally measured foot pressures and for the normal and leprosy subjects they are the highest in the push-off phase. In the leprosy subject with advanced TD, the highest soft tissue stresses and shear stresses (about three times the normal value) occur in push-off phase in the scar tissue region. The difference in shear stresses between the sole and the adjacent soft tissue layer in the scar tissue for the same subject is about three times the normal value. It is concluded that the high bone stresses in leprosy may be responsible for tarsal distintegration when the bone mechanical strength decreases due to osteoporosis and the combined effect of high value of footsole vertical stresses, shear stresses and the relative shear stresses between two adjacent soft tissue layers may be responsible for plantar ulcers in the neuropathic leprosy feet.

Finite Element Analysis↗

Leprosy: a close mimic in a rheumatology clinic.

Cutaneous and neurological manifestations of leprosy are readily diagnosed. However, physicians sometimes fail to recognize that leprosy may present with a rheumatic symptoms. A plethora of rheumatic manifestations are associated with leprosy, particularly with lepra reactions. A diligent examination for skin lesions/nerve involvement may uncover the diagnosis of leprosy in a patient referred for a rheumatological disorder. To highlight the fact that leprosy can mimic several rheumatological disorders, we have discussed a few representative cases seen over the past two years at our rheumatology clinic in a teaching hospital. In all these cases, a diagnosis of leprosy was made when the patient was referred for a rheumatic complaint.

Adult↗

Ocular leprosy in Hawaii: the past.

Leprosy in Hawaii dates back to about 1840. The first recorded ocular leprosy is from the 1880s. Robert Louis Stevenson and Jack London both wrote descriptions of the ocular signs of leprosy. Pinkerton in 1927 and Van Poole in 1934 reported large series of patients with ocular leprosy. In 1973 there were about 2,168 cases of leprosy in the 50 states. Most ophthalmologists practice in areas where there are leprosy patients.

Eye Diseases↗

Efficacy of single-dose ROM therapy plus low-dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion.

The recent World Health Organization multicentric field study on the treatment of paucibacillary (PB) leprosy patients with single skin lesion (SSL) and a single dose of rifampin-ofloxacin-minocycline (ROM) brought new hope to those who are engaged in the eradication of leprosy from India. Being encouraged by the WHO report, we undertook the present hospital-based study and found that PB leprosy patients with SSL were morphologically and histopathologically heterogeneous. The histological spectrum of SSL ranged from indeterminate through tuberculoid (TT) to borderline tuberculoid (BT) leprosy, and most patients had active BT leprosy. Ninety new, untreated PB leprosy patients with SSL were included in the present study for comparative assessment of the efficacies of ROM and ROM plus Convit vaccine therapies. Children, pregnant women, lactating mothers and patients with any thickening of nerves were excluded. All patients were bacteriologically negative (skin-smear test) but lepromin reactive. The patients were divided into two groups after proper matching for morphological and histological status of SSL: a) The test group included 60 patients and the control group included 30 patients. The test group was given a single dose of ROM initially and two injections of low-dose Convit vaccine, one initially and the other at the end of 3 months. b) The control group was given only a single dose of ROM initially. Both groups were followed clinically every 2 weeks for 6 months and retested for histological, bacteriological and lepromin status at the end of 6 months. Thereafter, they were followed clinically every month for another 6 months. In the test group, the SSL resolved in 33.3%, regressed in 48.3%, and remained active in 18.3% of the patients, while the granuloma disappeared in 70% of the cases. Only one patient developed neuritis, and in another patient the disease relapsed on the eighth month. On the other hand, the SSL in the control patients resolved, regressed and remained active in 13.3%, 63.3% and 23.3% of the cases, respectively, while the granuloma disappeared in 53.3% of the cases. In the seven patients who remained active, the disease course was progressive, and two of them developed neuritis. The clinical outcome of the patients treated with ROM plus low-dose Convit vaccine was statistically superior to those treated with single-dose ROM therapy alone.

Adjuvants, Immunologic↗

Knowledge and attitude of health professionals in relation to the integration of leprosy control into the general health service in Ethiopia.

Since the introduction of multidrug therapy for leprosy patients, the integration of leprosy control in the general health service (GHS) system has been an issue of debate. In Ethiopia, the present policy stresses integrated management of diseases. In spite of the policy, however, leprosy control was a vertical program until 1998 in most parts of the country. A descriptive cross-section study was conducted in the southern region of Ethiopia from October 1996 to March 1997 to determine the levels of involvement of the GHS staff and to identify obstacles to their involvement in the management of leprosy patients. Through a written questionnaire, data were collected from 240 GHS staff, including doctors, nurses and health assistants. It was found that 6% of the GHS staff was involved in leprosy control activities, mainly case finding and health education. Negative attitudes toward leprosy workers were held by 13% of the GHS staff while 40% had intermediate attitudes and the remaining 47% had positive attitudes. Statistically significant differences were found with regard to the level of knowledge among different health professionals, type of health institutions and years of service. The levels of involvement, knowledge and attitude of GHS staff showed that lack of integration and training were core problems. Hence, policy makers should give due attention to promoting the involvement of the GHS staff by integrating the program into the GHS system using the approach already in place in certain parts of the country.

Attitude of Health Personnel↗

[Manase Dosan (the Elder) and leprosy].

The aim of this paper is to describe the main features of Manase Dosan's (1507-1594) study and treatment of leprosy. Contrary to general medical opinion in the Middle Ages that leprosy was the result of divine retribution. Dosan viewed leprosy as simply another disease and treated it accordingly from a medical perspective. Furthermore, the commonly held belief from the latter half of the 17th century onwards amongst Early Modern era doctors and also the general populace that leprosy was a hereditary disease, was not considered by Dosan. The foregoing two points can be explained by his rational approach to medicine, plus the fact that leprosy at the time was widely prevalent amongst all areas of society, not just restricted to particular households. It is thus fair to say that Dosan's medical philosophy reflected the state of Japanese society during the transition from medieval to the Early Modern period. It should be noted, however, that Dosan's view that leprosy was caused by meat-eating and overindulgence in sex gave rise to a new, negative image of the disease, and in so doing tied in with the Early Modern era prejudices against "lust", "intemperance" and "laziness."

History, 16th Century↗

Socio-cultural aspects of leprosy among the Masalit and Hawsa tribes in the Sudan.

Social and cultural factors influencing knowledge, attitudes and practices (KAP) towards leprosy in two communities in eastern Sudan were studied to determine their effects on treatment seeking and compliance. The study was qualitative using focus small group discussions, personal interviews and direct observation. The target populations were Masalit and Hawsa, the two main tribes in the area. Knowledge about the pathological cause of leprosy was lacking but the clinical manifestations were well recognized, particularly among the Masalit, in whom the disease in more common than the Hawsa. Among the Masalit there was a widely held belief that leprosy was caused by eating meat of the wild pig and a certain type of fish. The Hawsa, who are more devout Muslims, do not eat pig and associate leprosy with consumption of two types of fish. Between both tribes, the stigma of leprosy was not strong and the degree of rejection was more towards those with severe disease, particularly patients with ulcerated lesions and severe deformities. Patients were cared for by the family and lived in a separate hut within the families' housing compounds. In this remote area where medical services are scarce or nonexistent, those interviewed did not realize that leprosy was treatable by modern medicine. This influenced the treatment-seeking behaviour of patients, who were often treated by spiritual healers and other traditional medicine practices. With the introduction of multidrug therapy and health education of patients and society, many more patients are now seeking medical treatment, indicating a change in health seeking behaviour.

Attitude to Health↗

Enhancement in the histological diagnosis of leprosy in patients with only sensory loss by demonstration of mycobacterial antigens using anti-BCG polyclonal antibodies.

This study was undertaken to assess whether the immunoperoxidase technique using anti-BCG serum is able to confirm the diagnosis of early leprosy among patients whose unique clinical manifestation is a localized area of sensory loss, in a higher proportion than the routine mycobacterial staining methods, namely hematoxylin-eosin and Wade. The study was held in the north of a hyper-endemic area of leprosy, Manaus, Amazonas (Brazil). Fifty-one paraffin-embedded skin biopsy blocks were retrieved and processed for the immunohistochemical study, by means of anti-BCG polyclonal antibodies for the detection of mycobacterial antigens. The routine stains confirmed the leprosy diagnosis in 17% of the cases, while the immunostaining method confirmed it in 47%. The McNemar test showed that the observed difference between these two techniques was statistically significant (p = < 0.05). In the same way, 50 blocks of skin conditions considered in the differential histopathological diagnosis of early leprosy were processed for the immunohistochemical test to analyze the possibility of false-positive results which occurred in 8 (16%) patients. The study suggests that immunostaining may increase the proportion of the routine histological diagnosis of leprosy in patients who have sensory loss only, even while using biopsies obtained in fieldwork conditions. This is very advantageous in hyper-endemic areas and in areas that are in the post-elimination period of leprosy control where sensory loss may be a sentinel sign of the disease.

Adolescent↗

Quantitative, histologic and ultrastructural studies of the index branch of the radial cutaneous nerve in leprosy and its correlation with electrophysiologic study.

A correlative study of clinical, electrophysiological, quantitative, histopathologic and ultrastructural changes seen in 13 instances of the index branch of the radial cutaneous nerve was undertaken in leprosy patients. Testing by graded nylon proved to be more reliable than any other conventional clinical tests. The quantitative studies revealed that small-sized fiber loss was encountered in the early stages of nerve involvement in leprosy followed by loss of large-sized fibers with or without increase in small-sized fibers. Segmental dymyelination of small-sized fibers was seen in early stages of degeneration in leprosy nerves irrespective of type of leprosy. Wallerian degeneration was encountered in advanced stages with total destruction of the nerves. At the ultrastructural level clinically normal nerves of leprosy patients (LN series) showed minimal but significant changes, such as thickening of the basement membrane of perineurial cells, as well as an increase in the amount of collagen between the perineurial layers. Marked increases in the amount of endoneurial collagen were noticed. Axons devoid of myelin, probably demyelinated fibers, were occasionally observed. Slight proliferation of the basement membrane of the endothelial cells was also observed. These changes were of a more advanced nature in the clinically involved cases of leprosy (L series). Two BL types of cases from the L series, showed presence of M. leprae in Schwann cell cytoplasm of myelinated and unmyelinated fibers, perineurial cells, in endothelial cells and macrophages. In cases having impaired sensory modalities (L series), thickening of the perineurium was due to increase in the number of layers of perineurial cells in addition to the increase in collagen. Probably one of the ways in which unmyelinated fibers degenerate is by splitting the Schwann cell columns and extrusion of the axons. Collagen pockets were seen in the LN series of cases. These are probably the degenerated nonmyelinated fibers being replaced by collagen fibrils. Postoperative clinical charting was done on the patient whose IRC nerves were removed. It showed complete restoration of all modalities of sensation in the area of its distribution by the end of three months.

Axons↗