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Among 50 patients with lepromatous leprosy and borderline lepromatous leprosy in Turkey, the prevalence of HLA-DR2 was 25/50 (50%). The prevalence of the same alleles among 50 healthy controls was 13/50 (26%).
We examined the structural requirements within the species-specific 3,6-di-O-methyl-beta-D-glucopyranosyl-(1 leads to 4)-2,3-di-O-methyl- alpha-L-rhamnopyranosyl-(1 leads to 2)-3-O-methyl-alpha-L-rhamnopyranose unit of the phenolic glycolipid I antigen of Mycobacterium leprae for binding to anti-glycolipid immunoglobulin M from human leprosy sera. We used chemically defined, partially deglycosylated fragments of phenolic glycolipid I, two other minor M. leprae-specific phenolic glycolipids (those containing 6-O-methyl-beta-D-glucopyranosyl-(1 leads to 4)-2,3-di-O-methyl-alpha- L-rhamnopyranosyl-(1 leads to 2)-3-O-methyl-alpha-L-rhamnopyranose and 3,6-di-O-methyl-beta-D-glucopyranosyl-(1 leads to 4)-3-O-methyl-alpha- L-rhamnopyranosyl-(1 leads to 2)-3-O-methyl-alpha-rhamnopyranose units), and phenolic glycolipids from other mycobacteria. Additionally, the trisaccharide of phenolic glycolipid I, the 3,6-di-O-methyl-beta-D-glucopyranosyl-(1 leads to 4)-2, 3-di-O-methyl-alpha-L-rhamnopyranose, the 6-O-methyl-beta-D-glucopyranosyl-(1 leads to 4)-2,3-di-O-methyl-alpha- L-rhamnopyranose, and the beta-D-glucopyranosyl-(1 leads to 4)-2,3-di-O-methyl-alpha- L-rhamnopyranose disaccharides were synthesized and characterized, and their activities were examined. Only the phenolic glycolipids containing 3,6-di-O-methyl-beta-D-glucopyranosyl at the nonreducing terminus were efficient in binding the anti-glycolipid immunoglobulin M, and the 3,6-di-O-methyl-beta-D-glucopyranosyl-containing di- and trisaccharides were the most effective in inhibiting this binding. Thus, the 3,6-di-O-methyl-beta-D-glucopyranosyl substituent was recognized as the primary antigen determinant in phenolic glycolipid I. With this information, bovine serum albumin containing reductively aminated 3,6-di-O-methyl-beta-D-glucopyranosyl-(1 leads to 4)-2,3-di-O-methyl- L-rhamnose was prepared and shown to be highly active in the serodiagnosis of leprosy.
The successful conclusion of the first leprosy eradication program carried out with combination therapy is reported. This program started in Malta in June 1972. It was based on extensive experimental and clinical studies and was formally concluded on 31 December 1999. No new infections occurred after the start of this 27-year progress report. The youngest patient was 16, and the eldest 83 years old. Of the total of 261 cases in the project, 201 had already received pretreatment [mainly with diaminodiphenylsulfone (DDS)] at the start. Sixty-one cases had no pretreatment. These were predominantly elderly patients who were late in deciding to have treatment. The very long follow-up period totaling 27 years was consistently maintained in order to be able to refute all potential objections empirically, e.g. with regard to relapses at a late stage. Besides the overall symptoms which are typical for the broad picture of leprosy, the involvement of the eyes was very striking (at least 50%). The therapeutic effect was of very rapid onset in these cases without surgery. Rifampicin (RMP) + isoniazid + prothionamide + DDS (trade name Isoprodian-RMP) was used as medication in a fixed combination. This fixed combination had already proved to be highly effective in the treatments during the course of the project, surprising therapy results (including lifesaving effects) were also noticed in other diseases.
A total of 410 patients (288 males, 122 females) aged between 9 and 60 years with an average age of 32.5 years were assessed for deformities of the eyes, hands and feet. The objectives were to find out the number and types of leprosy deformities in the leprosy population of the hospital, the proportion of those deformed among them and to establish the deformity baseline for the hospital. The study lasted 1 year, 38.78% (26.59% males, 12.20% females) of those investigated had one or more deformities. Apart from plantar and palmar insensitivity which accounted for 17.91% and 17.24% of all deformities, the most frequent deformities were mobile claw hand 12.94%, plantar ulcers 10.78% and palmar ulcers 5.97% respectively. With the exception of eye deformities, males accounted for a higher proportion of all deformities. Hand deformities were the most frequent of the three parts of the body studied. The patients' problems were highlighted and the need for adequate management and self-care were emphasized.
A Modified Leprosy Elimination Campaign (MLEC) in September 1998 in the District of Midnapore, West Bengal, covered a population of 8.1 million people and detected 8181 new cases. Available data from 7328 cases were studied to observe the trend for leprosy in this area. Data are presented on sex and age distribution, classification and the proportions of multibacillary (MB), paucibacillary (PB) and single skin lesion (SSL) cases discovered in a period of only 8 days. The large numbers of people examined in this district and the high total of new cases revealed are in keeping with experience in other parts of the State and in other parts of India. However, many cases were found in endemic areas and these will receive special attention in a second MLEC, planned for January 2000.
Patients with lepromatous leprosy (LL) but not borderline tuberculoid leprosy (BT) have defective cell-mediated immune responses to Mycobacterium leprae, despite normal responses to other stimuli, as judged by in vivo skin testing and in vitro lymphocyte transformation. To investigate the basis of the immune defect in LL patients, we studied the ability of patient mononuclear leukocytes to produce interleukin 1 (IL 1) and interleukin 2 (IL 2) upon stimulation with M. leprae, and determined the ability of exogenous IL 1 and IL 2 to reconstitute the LL patient response to this antigen in vitro. Equal numbers of adherent non-T cells from LL and BT patients produced similar amounts of IL 1 upon challenge with M. leprae, and addition of IL 1 to the culture medium failed to reconstitute the response of lymphocytes from LL patients to M. leprae. On the other hand, T cells of LL patients failed to express receptors for IL 2 or to produce IL 2 in response to M. leprae, whereas similarly treated T cells of BT patients both expressed IL 2 receptors and produced IL 2. Finally, recombinant human IL 2 purified to homogeneity as well as crude supernatants of mitogen-activated lymphocytes failed to reconstitute the response of LL patients to M. leprae. These results suggest that T cells of LL patients fail to respond to M. leprae despite an ability to produce IL 1 and that their failure to express receptors for IL 2 may explain both defective proliferation and the failure of exogenous IL 2 to reconstitute the response.
Leprosy bacilli of human origin were inoculated into a white-handed gibbon by the i.v. and i.p. routes, and also locally into ears, testis and around an ulnar nerve. The animal was observed closely during a period of nearly 15 years and did not exhibit any clinical evidence of cutaneous or neurological disease. At death, a wide range of tissues was taken for bacterial counts and histological examination, and a disseminated and progressive infection was demonstrated. Acid-fast bacilli were found in many sites; their morphological appearance distribution in nerves, and pattern of multiplication in mouse foot-pads, and also the presence of anti-mycobacterial antibody in the serum and the absence of specific lymphocyte transformation were all in keeping with an infection by Mycobacterium leprae, at an early lepromatous stage. This is probably the first fully documented report of experimental lepromatous infection in a primate. The findings are discussed in relation to the long incubation period of le promatous leprosy and the difficulties of diagnosing the disease at an early stage in man.
Certain Social and Related Factors responsible for 231 dropout leprosy patients from treatment are discussed. Dropout rate was lowest among lepromatous patients (1.2% Vs 10.9% among nonlepromatous patients); patients with stigma/deformity were significantly less (P less than .001); among dropouts; proportion of wage-earners was high in them (p less than .001); student dropouts were few (Z-2.78, P less than .05, X2 - 10.32, d.f.-1, P less than .005); there was little association between socioeconomic status and dropout rate (P greater than .5); dropouts amongst patients who self-registered for treatment were much less than in those who were enlisted for treatment during survey (P less than .05); 38% had dropped out within the first six months of registration for treatment; lepromatous patients attended clinics for more than 25 months before becoming dropouts; fear of loss of wages, belief that it was not leprosy, social stigma attached to the disease, disinterest for treatment when lesions were small and few, dissatisfaction with treatment, and belief that patches self-healed were the main causes for discontinuance of treatment; all those who dropped out due to shyness were women of 15-44 age-group.
The Hemerijckx leprosy centre at Polambakkam in South India covers a rural population of about 800,000 and has treated over 40,000 cases of leprosy during the period 1955-75. Based on a stratified random sample of 25% of the case records, information was obtained about the profile of newly-detected cases in various cohorts (1955-57, 1958-60, 1961-64, 1965-69, 1970-75), regularity in drug collection and response to treatment. In newly-detected cases, the ratio of males to females was stable (3:2), but the proportion of adults aged 45 years or more increased from 15% in 1958-60 to 20% in 1970-75 and the lepromatous rate decreased from 9% to 6%; the proportion deformed at the time of diagnosis ranged from 11% to 15%. Regularity in drug collection was unsatisfactory even in the first year of treatment, with less than half the patients making 6 (or more) of the 12 monthly drug collections. The clinical status at 4-6 years was known for 70-75% of the patients who started treatment and of those approximately 60% had inactive or arrested disease. Data from population surveys was sparse; about 60% of the expected numbers were initiated and less than 30% of these had a coverage of 75% or more. The limited evidence, however, showed a decline in the prevalence of about 2 per thousand per annum. Field studies to evolve strategies for better motivation of patients, introduction of short-course regimens, and continuous monitoring of the programme are urgently needed.
Analysis of records of urban leprosy clinic of the University Hospital, Varanasi for deformities was done for the years 1979 to 83. Gross deformity rate was 3.73 percent only. The majority of cases of deformity were in borderline type of leprosy. The commonest deformity was claw hand. It is discussed that dapsone treatment does not increase the chance of deformity. The rate, however, increased with age.
Occurrence of leprous pathology/bacilli in the internal organs in cases of polar tuberculoid leprosy, support the systemic nature and haematagenous transmission and spread of the disease process. Pathogenesis of leprosy has been postulated.
Study was conducted in 24 cases of various types of leprosy and 10 healthy controls to find out the effect of various sera on the T cell count of peripheral blood lymphocytes by sheep erythrocyte rosetting method. The percentage of T lymphocytes in lepromatous and tuberculoid cases were significantly lower compared to that in normal healthy controls. All sera except FCS had a stimulatory effect on the number of T cells. The cells incubated for 24 hours in FCS did not show any stimulatory effect on the number of T cells, however, these FCS incubated cells showed a significant elevation in the number of T cells when further incubated in sera either from leprosy cases or from healthy subjects.
A total of six index finger branch of the radial cutaneous (IRC) nerves from three BL, two BB and one BT cases of leprosy, with less than 6 months history of disease were subjected for nerve conduction velocity (NCV) studies followed by biopsy. The biopsy was divided into three parts and subjected for light microscopy quantitative histology, electron-microscopy and fibre tease studies. The nerves revealed a slight reduction in NCV and a varying degree of segmental demyelination ranging from 10% to 35%. The earliest changes observed were the thickening and proliferation of Schwann cell processes of the unmyelinated fibres and degeneration of their axons regardless of the type of leprosy.
Recently, there has been a sharp increase in the number of leprosy patients in The Netherlands, due to an increased immigration from Surinam where leprosy is hyperendemic. The patients registered at the Dermatological Department of the University of Amsterdam during the years 1972-1976 were reviewed. It was found that 28% of the untreated patients had recently suffered a relapse. A substantial percentage took the medication irregularly or discontinued treatment prematurely and quite a few patients required other types of treatment besides chemotherapy, such as surgical treatment and physiotherapy.
AIM: This is the second paper in a series of three papers on the occurrence of reactions and impairments in leprosy in Thailand, and focuses on the prevalence and incidence of reactions, including silent neuropathy. STUDY DESIGN: A population-based, prospective cohort study. STUDY POPULATION: All 640 newly diagnosed and registered leprosy patients in three neighboring provinces in northeastern Thailand 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: Clinical data and data on the sensibility and motor function of the eyes, hands and feet were obtained when appropriate. The occurrence of reactions, including silent neuropathy, at the beginning of, during and after treatment was ascertained. During surveillance mild late reactions were also recorded. RESULTS: Severe reversal reactions (RR) at the start of and during treatment were seen in 2.6% [confidence interval (CI) 1.1-4.1] of the PB and 29% (CI 23-35) of the MB patients. In the PB group the majority (82%) of severe RR were found at the start of treatment. In the MB group 35% of the severe RR were found at the start of treatment and another 59% during the first year of treatment. It is shown that there is a statistically highly significant increasing proportion of patients with severe RR starting from tuberculoid and going toward borderline lepromatous. The incidence rate of severe RR during treatment was 1.4 (CI 0.46-4.5) per 100 person-years at risk (PYAR) for PB patients and 12 (CI 9.0-16) per 100 PYAR for MB patients. Late (mild and severe) RR were seen in 2.7% of the PB and 9% of the MB patients (35% of these reactions being considered severe). Late reactions were mainly seen in borderline tuberculoid (PB group) and in borderline lepromatous patients. Recent silent neuropathies were seen at first examination and during treatment in 1.4% of the pB and 4.1% of the MB patients. During surveillance only a few silent neuropathies were seen. If all severe RR, severe erythema nodosum leprosum and silent neuropathies at the start of, during and after treatment were added together, then 53% of the borderline lepromatous and 42% of the lepromatous patients had or developed one or another serious complication in need of steroid treatment.
In Paraguay, the National Leprosy/Tuberculosis Program is based on a combined chemotherapy with isoprodian and rifampicin. The aim of this descriptive study was to investigate the therapy durations used so far in the treatment of 475 leprosy patients and to analyze the criteria responsible for the wide-ranging differences in therapy durations. As initial criteria, the following parameters were identified to have a significant influence on the therapy duration: Patients never treated before or pretreated, clinical classification and initial bacteriological index (BI) value. During therapy, conditions like the attendance and BI decrease/year showed a significant correlation with the therapy duration. Even though the studied criteria did not allow to draw a definite conclusion with regard to an 'ideal' therapy duration, they proved to be reliable, as only 2 patients have relapsed so far.
Charts of 1226 paucibacillary leprosy patients, registered between 1982 and 1987 were reviewed for recent facial nerve damage, facial patches and the presence of Type I reaction. Twenty-six (2.1%) patients with recent lagophthalmos were identified. In a great majority (85%) patients with recent lagophthalmos showed significant patches over the malar region or around the eye, at the same side as the nerve damage together with clinical signs of Type I reaction. This combination of significant patches in certain locations and Type I reaction seems to be a pre-condition for facial nerve damage. The clinical implication is that a small group of patients may be identified, who are at risk of facial nerve damage. By examining these patients more carefully it will be possible to detect nerve damage early and to prevent permanent damage of the facial nerve by timely treatment with an appropriate steroid regimen.
The cure rates of two treatment regimens in PB leprosy were compared in a prospective randomized trial: treatment U consisting of a single dose of rifampicin 40 mg/K bodyweight, and treatment A of rifampicin 1500 mg in a single dose, followed by one year of daily dapsone 100 mg. In patients with a BI = 0, the cure rates evaluated on the basis of histopathology of skin biopsies, were identical for the two regimens but in patients with a BI = 1, cure and relapse rates were unacceptable. For this reason and particularly the need to separate patients on the basis of the BI in skin biopsies, the single dose regimen does not appear to be suited for wide-scale application.