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Eye disease in multibacillary leprosy patients at the time of their leprosy diagnosis: findings from the Longitudinal Study of Ocular Leprosy (LOSOL) in India, the Philippines and Ethiopia.

Existing prevalence surveys do not provide adequate information to estimate the magnitude of ocular pathology or vision loss in leprosy patients. We sought to determine the prevalence of ocular findings and related risk factors in leprosy patients at the time of their disease diagnosis. We also sought to determine if there were geographic differences and whether these were due to different demographic characteristics of the populations. The study was undertaken at Schieffelin Leprosy Research & Training Centre (Karigiri, India), Leonard Wood Memorial Leprosy Institute (Cebu, Philippines), and (for 3 years only) ALERT (Addis Ababa, Ethiopia). Newly diagnosed multibacillary (MB) leprosy patients as well as MB cases relapsed after dapsone monotherapy were eligible for enrollment. In each study site, the target population was 300. Standardized examinations were conducted between 1991 and 1998. Patient enrollment included 301 patients in Karigiri, 289 patients in Cebu, and 101 patients in Addis Ababa. The age-adjusted prevalence of blindness (< 6/60 in the better eye) and visual impairment (6/24-6/60) was 2.8% and 5.2%, respectively. Lagophthalmos and leprosy related uveal changes were detected in 3.3% (95% CI 2.0-4.7%) and 4.1% (95% CI 2.4-5.7) of patients, respectively. Overall, 11% (95% CI 8.5-13.2%) of newly enrolled MB patients had potentially blinding leprosy related ocular pathology. Lagophthalmos was associated with increasing age, a short duration between onset and diagnosis, and a previous reaction involving the face. Uveal conditions were associated with increasing age. Overall, eye disease was more common in Indian and Ethiopian patients compared to Filipino patients; however, differences were not significant when controlling for age and clinical (non-ocular) factors. Patients with potentially blinding leprosy related pathology were over three times more likely to have other (hand and foot) disabilities than patients without pathology. Differences in the prevalence of blindness and potentially blinding leprosy related ocular pathology between the sites could be accounted for by the differences in age and other clinical factors of the patients at the different sites. Findings suggest that, even in the face of active leprosy control efforts, around 11% of patients will have potentially blinding pathology at the time of their diagnosis and 2.8% will be blind. If those patients with lagophthalmos or blindness are considered appropriate for referral for more detailed assessment, approximately 4% of newly diagnosed leprosy patients will require active follow-up for eye care; including those with reaction involving the face will result in 9.4% of patients requiring active follow-up. These people are likely to be older, with a reaction involving the face, and/or with other disabilities than those not requiring active follow-up.

Adult↗

In vitro stimulation of lymphocytes in leprosy patients, healthy contacts of leprosy patients, and subjects not exposed to leprosy. Comparison of an antigen fraction prepared from Mycobacterium leprae and tuberculin-purified protein derivative.

In vitro lymphocyte stimulation was performed on peripheral blood lymphocytes from 48 leprosy patients, 15 healthy contacts of leprosy patients, and 16 normal controls who lived in a leprosy-free area and who had not been exposed to leprosy. Tuberculin PPD and an antigen fraction. MLW 1, prepared from M. leprae, were used as stimulants. The MLW 1 preparation contained one antibody-precipitable component when tested in crossed immunoelectrophoresis against a polyvalent anti-M. leprae immunoglobulin preparation, namely the ML 7 antigen. MLW 1 induced strong lymphocyte responses in patients with tuberculoid leprosy and healthy contacts of leprosy patients, but only a weak or no responses in lepromatous leprosy patients and non-exposed controls. A marked depression of the response to tuberculin PPD was observed in lepromatous leprosy patients. The specificity of the MLW 1 antigen is discussed, and a new estimator of specific lymphocyte stimulation, the delta cpm', is introduced.

Adolescent↗

Occurrence of reactions, their diagnosis and management in leprosy patients treated with multidrug therapy; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

This paper reports on reactions in leprosy patients who were treated with multidrug therapy (MDT) in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. Only those reactions which occurred in patients who had not been treated with dapsone before MDT and which required treatment with prednisolone were included. Until the end of the second year of MDT a reversal reaction had been diagnosed in 43.6% of 266 borderline lepromatous (BL) patients and in 19.2% of 109 lepromatous leprosy (LL) patients, and an erythema nodosum leprosum (ENL) reaction in 2.7% and 11.1% of the patients, respectively. The reversal reactions were observed in 4.9% of the BL patients and in 0% of the LL patients at the time of diagnosis of leprosy, in 26.3% and 12.8% of the patients during the first year of MDT, and in 12.4% and 6.4% during the second year of MDT. ENL reactions were seen in 0.8% of BL patients at diagnosis, 1.1% in the first year and 0.8% in the second year and 2.8% at diagnosis, 5.5% in the first year, and 2.8% in the second year for LL patients. During a 3 1/2-year period, a total of 405 reactions were diagnosed among multibacillary (MB) patients on MDT; 365 of these reactions (90.1%) were reversal reactions and only 40 (9.9%) were ENL reactions. The point in time of the reversal reactions showed that the risk of reversal reaction is highest during the first year of MDT. Thereafter there is a gradual decline, although reactions were still observed during the fifth year of MDT. A reversal reaction was diagnosed in 21.0% of 438 BT patients; in 3.4% of the patients the reaction was present at the time of diagnosis of leprosy; in 10.3% it occurred during MDT, and in 7.3% during the first year after release from MDT. During a period of 3 1/2 years a total of 183 reversal reactions were diagnosed among BT patients. The point in time showed a declining trend in the risk of reversal reaction after starting MDT. The risk is highest during MDT, followed by the first 6 months after stopping MDT. However, reactions, although few, still occurred during the fourth year after stopping MDT. The analysis of the results of prednisolone treatment in 161 patients who were treated for nerve function loss in the field showed that 142 patients (88.2%) regained complete or partial recovery of the nerve function(s), while no improvement was observed in 19 patients (11.8%).(ABSTRACT TRUNCATED AT 400 WORDS)

Drug Therapy, Combination↗

Duration of multidrug therapy in paucibacillary leprosy patients; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Of 6042 paucibacillary patients who were put on MDT during a period of 7 years, 5485 patients (90.8%) completed the course of MDT; 437 patients (7.2%) did not fulfill the requirement for clinic attendance and either discontinued MDT themselves or the treatment was discontinued by the service. The remaining 120 patients (2.0%) either died, were transferred, left the control area or continued MDT after 9 months. The urine spot test for the presence of dapsone showed a significantly higher proportion of positive results for patients on MDT than for patients on dapsone. The analysis of the compliance with the prescribed doses of MDT showed that of 963 patients, 81.9% received six doses of MDT and 18.1%, more than six doses; 82.6% of these 963 patients attended with 100% regularity, 12.7%, 3.6%, and 1.1% missed one, two, or three clinic appointments, respectively, while fulfilling the requirement for overall clinic attendance. Of the 429 patients who had not been treated with dapsone before MDT, the skin lesions were clinically active at the time of stopping MDT in 130 patients (30.3%). In all, except one of the 114 patients (0.9%) who attended for follow-up examinations, the skin lesions had become clinically inactive within 2 years after stopping MDT. The recommended duration of MDT is discussed based on findings in the ALERT leprosy control programs and observations by others.

Dapsone↗

Relapses among leprosy patients treated with multidrug therapy: experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia; practical difficulties with diagnosing relapses; operational procedures and criteria for diagnosing relapses.

Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All African Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Paucibacillary (PB) patients are treated with 6 months of MDT. Multibacillary (MB) patients are treated with at least 2 years of MDT and until skin-smear negativity. An analysis was made of the relapses which had been diagnosed among self-reporting patients in four rural districts and Addis Ababa. Among 3065 PB patients, 34 relapses (1.1%) were diagnosed during an average period of 6.1 years after stopping MDT (range 2 1/2 to 7 1/2 years). Among 2379 MB patients, 24 relapses (1.0%) were diagnosed during an average period of 4.7 years after stopping MDT (range 2 1/2 to 6 years). The estimated relapse rate per 1000 patient-years after release from MDT was 2.1 for PB patients and 2.4 for MB patients. From the analysis of the clinical, bacteriological, and histopathological findings, it was concluded that there was strong positive evidence for the diagnosis for 16 of the 34 relapses in the PB patients and for 0 of the 24 relapses in the MB patients. The main cause for overdiagnosis of MB relapses was that too much reliance had been put on skin-smear results, without a careful comparison of the results with those from before, during, and at completion of MDT; the diagnosis was based on the finding of positive smears in one set of smears only; insufficient attention was given to finding solid-staining bacilli; and findings in biopsies, if these were examined, did not confirm the diagnosis. The main cause of overdiagnosis of PB relapses was that too much reliance was put on histological findings, while these are often inconclusive for differentiating between a relapse and late reversal reaction. Recommendations are made on how to limit overdiagnosis of relapses. Operational procedures and criteria for making the diagnosis under conditions where facilities for back-up histological and mouse foot pad investigations are not available are proposed.

Clofazimine↗

Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT.

Adolescent↗

Experience with WHO-recommended multidrug therapy (MDT) for multibacillary (MB) leprosy patients in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center in Ethiopia: appraisal of the recommended duration of MDT for MB patients.

During 1981 a World Health Organization Study Group recommended that multibacillary (MB) leprosy patients should be given multidrug therapy (MDT) for at least 2 years and, wherever possible, until skin-smear negativity. This paper reports on the experience with MDT for MB patients under routine field conditions in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in the Shoa Region of Ethiopia. The period of MDT to reach skin-smear negativity was evaluated for 348 new MB patients. Only 31.6% of these patients could be released after 26 four-weekly doses of MDT, and 19.8% needed over 5 years of MDT. The average period of MDT to reach skin-smear negativity was estimated at about 4 years. Of 3343 patients of cohorts which, almost exclusively, consisted of patients treated with dapsone before MDT, 72.8% were released after 26 four-weekly doses of MDT; whereas of 712 patients of cohorts which mainly included new patients, only 23.5% were released. It was estimated that if MDT would be stopped, regardless of skin-smear results, after 26 four-weekly doses of the drugs collected within a period of 3 years, about 80% of the patients would complete treatment. The operational problems with continuation of MDT until skin-smear negativity are discussed. Although as yet it has not been proven by study results that after 2 years of MDT the relapse rate will be low, the available knowledge indicates that this is likely to be the case. Based on a) probability, b) the finding that 2 years of MDT can be maintained in the majority of the patients, and c) the operational difficulties with the continuation of MDT until skin-smear negativity, it is recommended that MDT should be limited to 2 years. MDT of limited and fixed duration will facilitate the implementation and expansion of the treatment in parts of the world where most patients are not yet benefitting from this treatment.

Cohort Studies↗

Patterns of indoor admissions of leprosy patients in pre-MDT and post-MDT era and a role for leprosy referral hospital in leprosy integration programme.

Analysis of the admission patterns in a leprosy referral hospital during the last 27 years (1966 through 1993) shows a decrease in the number of annual admissions since 1987. While there were 1550 admissions during 1981-1983, only 842 patients were admitted during 1991-1993. There was no great change in the reasons for admission, about 46% for reactions, 37% for ulcers, 5% for neuritis and about 12% for other problems. However, compared to the pre-MDT days, admissions for neuritis have increased. A case is made for the continuation of special leprosy referral hospital even beyond the year 2000 AD, i.e., even after elimination of leprosy as a public health problem.

Adolescent↗

Experimental murine leprosy. IX. Antibodies against Mycobacterium lepraemurium in C3H and C57BL mice with murine leprosy and in patients with lepromatous leprosy.

Sera from C3H and C57BL mice infected with Mycobacterium lepraemurium (MLM) and from human leprosy patients were examined for antibodies against MLM by a crossed immunoelectrophoresis (CIE) technique. Altogether antibodies against six or seven MLM antigens were found in the mouse sera. After a small inoculum of MLM, C3H mice produced more antibodies than C57BL mice. After a large inoculum both strains produced about the same amount of antibodies but showed qualitative differences in their response patterns. A serum pool from patients with lepromatous leprosy contained antibodies against six MLM antigens; five of these were identical with the antigens against which antibodies were found in infected mice. C57BL mice that had lost their delayed-type hypersensitivity to MLM during the course of a disseminated infection showed a fairly strong antibody response to three antigens and a weak response to three others. Since almost the same spectrum of antibodies, although in lower titres, could be demonstrated in C57BL mice with intact delayed-type hypersensitivity to the bacilli, these antibodies did not seem to interfere with the expression of cell-mediated immunity.

Animals↗

Comparative study of the 48-hour response to soluble antigens obtained from human and armadillo leprosy material in lepromatous leprosy patients and normal persons, contacts of leprosy patients.

We prepared antigens by precipitating with 80% ammonium sulfate supernatants of human and armadillo antigen at a concentration of 160 X 10(6) bacteria per ml. The precipitate was resuspended, dialyzed and filtered. The antigen obtained was inactivated with trypsin during 30 minutes. The tests made with these antigens were negative for the 48-hour test in lepromatous patients and highly positive in normal persons who were contacts of leprosy patients.

Animals↗

Models for leprosy. An appraisal of graphic representations of the "spectrum" concept as models and a suggestion for a catastrophe theory model for leprosy.

Graphic representations of the spectrum concept of leprosy are examined in some detail as models for this disease. This reveals that this concept is somewhat inadequate and that the spectrum metaphor may itself be inappropriate because, by its very linearity of logic, it may not be able to depict the nonlinear behavior of leprosy properly. The assumptions underlying this concept and their logical consequences, brought out by the graphic representations, include an invariable relation between CMI and BI, identity of one type of leprosy with one specific level of CMI, a fixed sequence of types, and the consequent impossibility of skipping the sequence. However, our experience with leprosy does not bear out these assumptions. Further, development and progress of leprosy from a normal (nonleprous) state cannot be represented in these models. A search for alternative conceptual models therefore appears reasonable and even necessary. The catastrophe theory (a branch of topology in mathematics) describes a number of models for explaining how continuous causes could produce sudden or discontinuous changes. Of the various catastrophe theory models available, the relatively simple "cusp" model appears capable of application to leprosy. This model, as applied here, requires two control factors (identified tentatively as the amount of dead bacilli and the amount of living bacilli or their indicators) and one pattern of behavior, identified as progress towards limited or extensive disease. This model suggests under what conditions leprosy will change from one type to another and whether that will happen gradually or suddenly. It also suggests that for certain values of control factors the disease may manifest in one of two forms of borderline leprosy, and that lesions very similar to start with can progress to quite different states under similar conditions of change. The behavior of leprosy agrees more or less with that suggested by this model. The cusp model thus seems to: a) provide an insight into the behavior of leprosy, enabling us to understand the dynamics of the disease; b) explain some of its intriguing manifestations; c) ask meaningful questions; and d) plan new therapeutic approaches. Although this is a highly speculative and probably too simple a model, this attempt shows that it is possible to view leprosy outside the framework of the concepts of spectrum scale and polar types of leprosy, the conceptual models which dominate all of our current thinking about the disease.

Humans↗

Leucocytic alkaline phosphatase activity in leprosy: a possible guide in the follow-up of leprosy.

In order to investigate a possible involvement of phagocytic cells in the various types of leprosy, we undertook the study of enzymatic activities in circulating leucocytes. The activity of leucocytic alkaline phosphatase was studied by histochemical techniques on blood smears in 31 patients presenting with leprosy and aged between 4 and 73, and in 11 non infected people. The 31 patients suffering from leprosy were distributed as following: 14 lepromatous leprosy of which 6 had not yet been treated and 8 were under treatment, 9 cases of tuberculoid leprosy of which 7 had been treated and 2 had not yet, 3 cases of borderline leprosy which had all been treated, and 5 patients whose form of leprosy was indeterminate (before treatment). The distribution of the different values we obtain shows a very significant difference (p less than 0.001) between patients with and without leprosy (respectively 33.8 +/- 7.3 and 109.8 +/- 12.5). Moreover, the decrease of the alkaline phosphatase activity correlated with the severity of the disease (47.2 +/- 11.4 in tuberculoid leprosy and 20.6 +/- 9.3 in lepromatous leprosy) thus suggesting that the evaluation of leucocytic alkaline phosphatase activity should be advised as a possible prognosis guide in indeterminate leprosy.

Adolescent↗

Lesional T-cell subset in leprosy and leprosy reaction.

BACKGROUND: The T-cell-mediated immune response plays an important role in leprosy. The in situ proportion and pattern of distribution of T-cell subsets in leprosy skin lesions have been studied, but no conclusion could be drawn. METHODS: We used monoclonal antibodies for T-helper and T-suppressor surface antigen to define the nature of dermal infiltration in 17 cases of nonreactional leprosy and 20 cases of reactional leprosy. RESULTS: We found T helper admixed with T suppressor in an aggregated pattern in the granulomas of most cases of nonreactional leprosy and in type I reactional leprosy, but a diffuse infiltrate throughout the dermis of type II reactional leprosy. The T-helper/suppressor ratio was 1.68 in tuberculoid and 1.5 in lepromatous cases. The T-helper/ suppressor ratios of borderline tuberculoid (3.11) and type I reactional leprosy (2.54) were not statistically different. The T-helper/suppressor ratio of type II reactional leprosy (5.83) was statistically higher than nonreactional lepromatous cases. CONCLUSIONS: The alteration of the T-helper/suppressor ratio in our study is mainly due to the reduction of T-suppressor cells in the dermal infiltrates, especially in type II reactional leprosy. Further studies of T-suppressor functions may be important in the pathogenesis of leprosy.

CD4 Antigens↗

Leprosy case detection rates by age, sex, and polar type under leprosy control conditions.

The knowledge of leprosy epidemiology is still extremely limited as to basic epidemiologic characteristics. Only the infectious agent and the reservoir of infection have been firmly established. It is all the more surprising that very few studies of analytical leprosy epidemiology are reported in the literature. In order to contribute to the analysis of these characteristics, data are presented on the age and sex distribution of types of leprosy from the Pogiri Leprosy Control Project, a large leprosy control project in Andhra Pradesh, India. This data base includes records on biannual examination of some 160,000 household contacts of nearly 48,000 leprosy cases observed from five to nine years between 1962 and 1970. These data indicate a peak of leprosy prevalence and incidence in the age group 35-44 years. The sex differential in leprosy, observed in these data, appears more related to sex differences in social contact, as sex ratios of leprosy vary widely among different populations. Finally, the age distribution of tuberculoid leprosy shows a bimodal curve, with peaks at ages 10-14 and 35-44 years. The first peak appears related both to the occurrence of early and self-healing lesions in school children, and to the more frequent examination of school children. Additional observations are presented on type ratios of leprosy in single and multiple case households, and on per cent of single lesions for tuberculoid cases detected over time.

Adolescent↗

Immunoglobulin class specific antibodies to M. leprae in leprosy patients, including the indeterminate group and healthy contacts as a step in the development of methods for sero-diagnosis of leprosy.

IgA, IgM and IgG anti-M. leprae antibody activity was quantitated by solid phase radioimmunoassay in groups of untreated leprosy patients throughout the spectrum, in lepromatous leprosy patients treated for more than 10 years, in an indeterminate leprosy group, and in a non-leprosy control group. IgA, IgM and IgG anti-M. leprae antibody activity increased from the group of healthy individuals exposed to M. leprae but without clinical signs of leprosy to tuberculoid (BT and BT/TT) and further to lepromatous (BL to LL) leprosy. There was a considerable overlap in IgA antibody activity, while the overlap between controls and tuberculoid and lepromatous leprosy was less than 20% in the IgM and IgG assays. After more than 10 years of treatment, the IgG anti-M. leprae activity had decreased markedly, whereas there was less effect in the IgA assay and no significant change in the IgM assay. In contrast to earlier findings, the group of 'strictly indeterminate leprosy' showed signs of an active humoral immune response against M. leprae. The IgM anti-M. leprae activity was higher in indeterminate leprosy than in the control group with virtually no overlap. IgA anti-M. leprae was higher in indeterminate leprosy, but with considerable overlap with the controls. No difference between these two groups was found in the IgG assay. The results are discussed in relation to the value of the various immunoglobulin specific anti-M. leprae assays for different purposes, including development of techniques for sero-diagnosis of leprosy.

Antibodies, Bacterial↗

Cytokines in leprosy, I. Serum cytokine profile in leprosy.

BACKGROUND: Leprosy is a chronic infectious disease characterized by a broad spectrum of clinical forms depending on the patient's immune response, in particular cell-mediated immune response. METHODS: Cytokines can play a role in the cell-mediated immune response. Serum levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-2 receptor (IL-2R), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA) in 55 untreated leprosy patients and 35 reactional leprosy patients, in addition to 20 age- and sex-matched healthy controls. RESULTS: Leprosy patients showed significantly higher serum levels of the studied cytokines (except IL-2) compared with healthy controls. When the two poles were compared, tuberculoid leprosy (TT) patients showed significantly higher levels of IFN-gamma and TNF-alpha with significant negative correlations with the bacterial index (BI), whereas lepromatous leprosy (LL) patients showed significantly higher serum levels of IL-2R, IL-10, and IL-1beta with significant positive correlations with the BI. Both type I and type II reactional patients showed significantly higher serum IFN-gamma, IL-2R, and IL-1beta, in addition to IL-10 in type II reactional patients, compared with nonreactional leprosy patients. When compared with each other, type I reactional patients showed increased levels of IFN-gamma, whereas type II reactional patients showed increased levels of IL-10. CONCLUSIONS: In leprosy patients, both IFN-gamma and TNF-alpha are immunoprotective, whereas IL-2R, IL-10, and IL-1beta are immunosuppressive. Our results indicate that type I reaction, with increased levels of IFN-gamma, is a cell-mediated immune response, whereas type II reaction, with increased levels of IL-10, is essentially an immune complex disease.

Cytokines↗

Segregation of HLA/TNF region is linked to leprosy clinical spectrum in families displaying mixed leprosy subtypes.

Each year an estimated 600000 new leprosy cases are diagnosed worldwide. The spectrum of the disease varies widely from limited tuberculoid forms to extensive lepromatous forms. A measure of the risk to develop lepromatous forms of leprosy is provided by the extent of skin reactivity to lepromin (Mitsuda reaction). To address a postulated oligogenic control of leprosy pathogenesis, we investigated in the present study linkage of leprosy susceptibility, leprosy clinical subtypes, and extent of the Mitsuda reaction to six chromosomal regions carrying known or suspected leprosy susceptibility loci. The only significant result obtained was linkage of leprosy clinical subtype to the HLA/TNF region on human chromosome 6p21 (P(corrected)=0.00126). In addition, we established that within the same family different HLA/TNF haplotypes segregate into patients with different leprosy subtypes directly demonstrating the importance of this genome region for the control of clinical leprosy presentation.

Chromosomes, Human, Pair 6↗

[Epidemiological immunological studies on leprosy in Okinawa. 6. Lepromin, lymphocyte transformation, FLA-ABS and leproagglutination tests in the in-and out-patients with leprosy and the relationships among these tests and personal or family history or clinical findings of the patients].

In- and out-patients with leprosy in Okinawa were surveyed by using the following immunological tests: cutaneous reaction to Mitsuda's lepromin (40 million bacilli/ml) (LPR), lymphocyte transformation test with Dharmendara's antigen (DL-LTT), that with phytohemagglutinin (PHA-LTT), fluorescent leprosy antibody absorption test (FLA-ABS) and Leproagglutination test with cardiolipin-lecithin antigen (LAT). A correlation between two tests and a relationship between the test and personal or family history or clinical finding of the patients were evaluated by non-parametric statistics. Spearman's rank correlation coefficient was significant between LPR and DL-LTT, while a reverse correlation was found between LPR and FLA-ABS, DL-LTT and FLA-ABS, and DL-LTT and LAT, respectively. High reactivity in PHA-LTT was found in almost all of patients, irrespective of type and stage of leprosy, suggesting general immune responsiveness of leprosy patients in Okinawa. The other tests showed a significant difference in the mean rank of reaction values according to clinical findings such as type and stage of leprosy, property of skin lesion, loss of eyebrow, and bacteriological test. The use of LPR and DL-LTT for the study of cell-mediated immunity in leprosy was therefore confirmed. FLA-ABS was found useful for early serodiagnosis, while LAT for the study of autoimmunity in leprosy. None of these immunological tests showed significant difference among the subgroups of patients classified by the following items: presence or absence of consanguineous patient with leprosy, living place, place of onset, presence or absence of neural symptoms such as the enlargement of peripheral nerve, claw hand and facial palsy, ocular and nasal involvement, ENL in lepromatous and borderline leprosy and conditions in the treatment. On the other hand, LPR showed higher reactivity in female than in male, in the patients at home than those discharged, and in the patients with drop foot than those without. Higher reactivity of DL-LTT was also found in male than in female and in the patients with plantar ulcer than those without. FLA-ABS reactivity was significantly higher in the discharged patients than the inpatients, in the period of 5 to 9 years after onset than that of 20 or more years, but the reactivity was lower in the patients with drop foot than those without. LAT reactivity was significantly higher in the 30-39 years old patients than 0-19 years old, and in the patients with physical work than those with mental.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗