Human leukocyte antigens (HLA) class II alleles were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist among the forms of leprosy in classification of World Health Organization-recommended multidrug therapy (WHO-MDT). The subjects were 86 unrelated Japanese leprosy patients, including 62 multibacillary leprosy (MBL), 24 paucibacillary leprosy (PBL). Controls were 114 unrelated healthy subjects. Genotyping of HLA class II alleles was performed by using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequencies of HLA-DRB1* 1501, * 1502 and DRB5* 0101,* 0102 and DQA1* 0102 and DQB1* 0602 were significantly increased in the whole patients (44.2%, 34.9%, 44.2%, 34.9%, 53.4% and 41.9%, respectively) as compared with the control subjects (14.0%, 21.1%, 14.0%, 21.1%, 27.2% and 13.2%, respectively). On the other hand, the frequencies of HLA-DRB1* 0405, * 0803, * 0901 and DQA1* 03 and DQB1* 0401 were significantly decreased in the whole patients (10.5%, 5.8%, 16.3%, 41.9% and 9.3%, respectively) as compared with the control subjects (29.8%, 17.5%, 30.7%, 78.1% and 29.8%, respectively). When MBL and PBL patients were compared, the frequencies of HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 were significantly increased in the MBL patients (51.6%, 51.6% and 48.4%, respectively) as compared with the PBL patients (25.0%, respectively). Our results suggest that HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 contribute to the susceptibility to the Japanese MBL.
Leprosy is a chronic disease and a major health problem in Thailand because it is a communicable disease involving of the nervous system causing deformation in severe cases.The Leprosy Control Program in Thailand was started on 1909 and continuing its operation presently.The Leprosy control activties were deviled into 4 phrase as follow.(1,2) 1.Initial isolation phrase.In the initial phase there was an estimated 10,000 leprosy patients.During this period in time the only effective drug was Dapsone.At this time all Leprosy patients were isolated to Leprosalium, Mckane Leprosalium, for treatment.This isolation was an effective way of stopping the furthur
A gelatin particle agglutination test (MLPA) for the detection of anti-phenolic glycolipid-1 (PGL-1) antibodies was compared with the slit skin smear method in the diagnosis of leprosy. MLPA and BI tests showed a good agreement rate of 88.1% and MLPA and ELISA tests showed an excellent agreement rate 96.2%. This MLPA test is simple and reliable, it will be very convenient for the medical practitioners, it would be of great benefit for leprosy patient as well because this test would look like a routine blood examination compared with slit skin smear method which is widely known diagnostic tool for leprosy.
BCG vaccine (Tokyo strain) was given in BALB/cA mice intradermally 1 or 3 months before Mycobacterium leprae (M. leprae) challenge as modified Shepard's method. The vaccine dosage was 10(7-8) or 10(6). The BCG gave good protection in both dosages and both challenges against M. leprae infection. Lymphocytes proliferations of BCG-vaccinated splenocyte cultures in response to M. leprae lysate or BCG components (hsp65, 38 kD, 30 kD or 12 kD protein) were tested, and potent proliferative responses were seen in the cultures with M. leprae lysate and hsp65. Furthermore, gamma-IFN productions were positive in the cultures with M. leprae lysate or hsp65, but negative with other antigens. The production of gamma-IFN with hsp65 was never inhibited with polymyxin B, but inhibited with IL-10. These results show that BCG (Tokyo strain) is a useful vaccine for M. leprae infection in mice, and one of the components of BCG, hsp65, may be a effective antigen component for protection of M. leprae infection inducing Th1 type cytokine.
In the previous paper, it was indicated that the activity (ATP values extracted from collected cells) of Mycobacterium leprae could be maintained in the phosphate buffer (pH 7.0) containing fetal calf serum (10%) for more than 4 weeks under the incubation at 30 degrees C. The present paper describes that the activity of cells of M.leprae is prolonged and somewhat stimulated when glycerin and dextran are added to the buffer serum system. The optimal concentrations for glycerin and dextran are 2% and 1%, respectively. In addition, it is found that the dextran of MW. 200,000-300,000 is much more effective than that of MW. 100,000-200,000.
Neurotropism is one of the most important characteristics of Mycobacterium leprae (M. leprae). It is believed that nerve damage of leprosy is caused by various immune mechanisms 1), and so called "autoimmune reaction" is suspected to have one of the role in nerve damage.M. leprae 65 kDa heat-shock protein (hsp65) has noticeable characteristics. Hsp65 is a highly conserved protein2). Itbelongs to the family of groEL proteins3). The amino acid sequence of M. leprae hsp65 shows homology of more than 90% with other mycobacterial hsp65s and shares around 48% amino acid identity with the mammalian mitochondrial P1 or hsp 604). Hsp65 was also reported to be a highly immunogenic protein of M. leprae in both Bcell and T-cell responses5, 6). Recently, many reports have described the relationships between hsp65 and some autoimmune diseases such as Kawasaki disease7), rheumatoid arthritisa8) and so on; the role of hsp65 in immunological disorders may be one of molecular mimicry9). Freedman et al described the expression of hsp 60 and hsp 70 by human glial cells. Such hsps were supposed to be the recognition molecule (s) for γ δT cells which mediated glial cell lysis in uitro 10 There are no providing mechanisms for nerve damage in leprosy just now, but the molecule(s) of hsp65 may at least be the possible candidate as a recognition molecule for γ δT cells generated during M. leprae infection.In this paper we reported stablishment of mouse cell lines showing stable expression of M. leprae hsp65, such cell lines would work as a target cell in cytolysis assay in vitro for cytotoxic T cells and γ δT cells generating during M, leprae infections.
We examined 24 dermatologically cured leprosy patients with ongoing uveitis (UV+) and 22 age and type matched controls (UV-) to study the late phase leprous UV. All patients have been skin smear negative for more than 10 years. The history of chemotherapy, 5 years before and after a accomplishing bacterial negativity, was evaluated and represented by "SCORE". It was found that anti-PGL-I and anti-LAM-B antibodies were significantly higher in UV+ group compared to the controls. The mean SCORE of chemotherapy in UV+ group was significantly lower than in the controls. Iris pearls were seen in 10 cases or 42% out of 24 UV+ patients. No iris pearls were seen in control group. These results suggest that insufficient chemotherapy and consequent incomplete elimination of bacilli are the risk factors for leprous UV in the quiescent stage of the disease.
This paper report the progress and impact of MDT implementation to leprosy control in Thailand since 1984 until 1994. By ten years of MDT implementation, number of registered cases dropped from 44,406 in 1984 to only 4,878 cases in 1994. Which made prevalence rate declined 90% from 8.8 to 0.83 per 10,000 population, the detection rate of new case declined from 6.2 to 1.97 per 100,000 population. Total 39,372 cases have been completely covered by MDT and 22,821 cases are under post MDT surveillance with the low relapse rate only 1.46% other indicators showing natural decline of leprosy were increasing in proportion of multibacillary leprosy and mean age at onset of new case of leprosy together with decreasing in proportion of children among new case. Other impact of MDT showing increasing trend of proportion of new case of patient who voluntarily attend treatment centers. However, there were still no satisfactory impact on decreasing in proportion of deformity and duration since onset to the first detection of new case of leprosy.
We studied dermal connective tissue of leprosy patients(Pa) in inactive condition. The dermal thickness(D) and the volumes of collagen and elastic fibers were measured utilizing automated computerized image analyzer. The length of each elastic fibers(E) in lower legs were also measured. The E in upper dermis of forearms were observed microscopically. All these were compared with age-matched control(Co). We got the following results accordingly. There was a relative increase of E in Pa's limb skin in spite of greatly decreased dermal thickness and fibrous components. The influence of sun exposure could not be recognized in this result. Each elastic fibers of Pa were longer than that of Co. The increased E in upper dermis was evident in Co's forearms, but not in Pa's. From our results, it is conceivable that the Pa's E either outlast or are overproduced exceedingly the collagen fibers. The factors that may account for these results are remained to be clarified.
リファンピシン,ダプソン,クロファジミンなどよりなるらいの多剤併用療法の普及によりらい有病率は著しく低下したが,更に強い抗らい菌活性を有する新規薬剤並びに多剤併用レジメンを開発することにより優れた短期•間欠療法の方式を確立することが望まれる。本総説では諸種の抗らい剤の研究の現況について解説し,併せて将来の問題点についてもふれるところがあった。
A 67-year-old patient has had exanthema in the lower right limb since 51 years ago (16 years old at onset), which underwent repeated remission and recurrence. At present, he has bilateral symmetrical widespread infiltrating exanthema and asymmetrical marked neuralhypertrophy, and has been diagnosed typical LLs (His father had the same disease). The exanthema recurred several years ago, and the patient is being treated for Hansen's disease. He had a dark brown flat elevation with a rough surface and the size of a small finger tip in his right abdominal skin for approximately 20 years. A biopsy was performed, and the specimen was fixed in 10% formalin and paraffin sections were prepared for histopathologic examination. A part of the specimen was processed forscanning electron microscopic examination. Seborrheic keratosis was diagnosed by H & E staining. Acid-fast (FITE) staining, immunohistochemical staining (keratin, S-100 protein, anti-PGL antibody and anti-BCG antibody) and scanning electron microscopy revealed the presence of bacteria (M. leprae) in the dermal foam cells, the matrix with a banded structure and the squamous epithelial cells which normally lack phagocytosis function. Compared to the basal cells of normal epidermis, the basal cells located adjacent to the dermis affected with seborrheic keratosis showed increased proliferation and more marked characteristics of a germinative cell. The degree of differentiation of the basal cells appeared regressed, and they probably possessed augmented phagocytic activity. The phagocytosed bacteria were probably carried by the epidermal cell cycle toward the surface layer. However, bacteria could not be found in the stratum corneum, probably due to an association with the lysosome.
The clinical spectrum of leprosy reflects the diverse nature of human immune responses to Mycobacterium leprae. The clinical presentations correlate with the level of cell-mediated immunity against M. leprae. Cell-mediated immunity, as assessed by the Mitsuda reaction, is positive in tuberculoid patients and negative in lepromatous patients. In contrast, humoral immunity, as assessed by anti-M. leprae antibodies is greatest in lepromatous patients. The inverse correlation between cell-mediated immunity can be explained on the basis of the local cytokine pattern.
