ad hoc committee of Japanese Leprosy Association recommends revised standard treatment protocol of leprosy in Japan, which is a modification of World Health Organization's multidrug therapy (WHO/MDT, 1997). For paucibacillary (PB) leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough. However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment seems insufficient. Thus, (A) For MB with bacterial index (BI)≥3 before treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary.. When BI become negative and active lesion is lost within 2 years, no maintenance therapy is necessary. When BI is still positive, one year of MDT/MB is added (3 years in total), followed by maintenance therapy by dapsone and clofazimine until BI negativity and loss of active lesions.(B) For MB with BI<3 or fresh MB (less than 6 months after the onset of the disease) with BI≥3, 1 year treatment by MDT/MB is necessary. When BI become negative and active lesion is lost within one year, no maintenance therapy is necessary. When BI is still positive or active lesion is remaining, additional therapy with MDT/MB for one more year is recommended. This is a simplification of first version in 2000. Brief summary of diagnosis, purpose of therapy, character of drugs, and prevention of deformity is also described.

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Antimicrobial susceptibility testing of Mycobacterium leprae by non-radioactive bioluminescence assay was developed. Optimization of the assay conditions such as temperature and time for ATP extraction, bacteria dose, preparation of bacteria suspension and pH of culture medium was carried out using M. leprae Thai 53 strain. Samples of bacterial suspension of M. leprae were first treated with filamentous cell treatment reagent at room temperature for 30 minutes and ATP was extracted from the leprosy bacilli by heating at 60 degrees for five minutes. Luciferin luciferase was added to the extract after cooling to room temperature followed by measurement of relative light units (RLU) of each sample using a luminometer. The concentrations of the drugs used for the evaluation of antimicrobial activities of rifampin (RFP), clofazimine (CLF), ofloxacin (OFLX) and clarithromycin (CAM) were 0.125, 0.50, 2.0 and 8.0μg/ml respectively. Middlebrook 7H9 broth medium was used (pH6.6) as the basal medium and the bacilli were cultivated at 32°C for 0-14 days. ATP was extracted from 0.1ml of culture suspension and inhibition of the luminescent activity was calculated. The results were compared to that obtained by radio-active CO₂ detection system, Buddemeyer method which is commonly used for measuring anti-M. leprae activity.
There was a good correlation between the results obtained by ATP method on the tenth day of culture and the results obtained by Buddemeyer method on the seventh day of culture. ATP method may be useful for the determination of drug susceptibility of M. leprae.

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The elimination of leprosy with the advent of multidrug therapy (MDT) is one of the success stories in public health. Elimination will be achieved in the regions of Western pacific and South-East Asia in near future. A biregional consultation between the WHO South-East Asia and Western Pacific regions was held in the end of 2004 in Manila, the Philippines. A strategy document was developed during the consultation, to sustain quality leprosy services in Asia and the Pacific beyond 2005, and to further reduce the leprosy burden. The main strategy involves timely detection of new cases, multidrug treatment, and the key element of integration of leprosy services into general health services.

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Most of 148 newly registered leprosy patients in the past 10 years from 1995 to 2004 in Japan had received some examinations, such as histopathology test (85%), skin smear test (84%), estimation of PGL-I antibody titer (55%) or detection M. leprae with PCR method (41%).
17% of newly patients should receive wrong therapy, if they hadnot had aforesaid clinical examinations in addition to count skin lesions.
Improvement of technical level at skin smear test should be required for accurate treatment program in Japan.
In Japanese patients, the number has been decreasing year by year; epidemiological condition was different between in Okinawa prefecture and in others, about ratio of sex, kind of type and age group.

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We present the situation of leprosy in Brazil, reporting about epidemiology, clinical criteria for classification, multidrugtherapy and special situations, as co-infection. This material was presented in the 79th Annual Meeting of Japanese Hansen's Disease Association in May 2006, during a discussion about the Japanese Guidelines for leprosy treatment.

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Laboratory tests necessary for the diagnosis of leprosy have not been well introduced in general hospitals and clinical laboratories. Therefore, several tests have been performed in Leprosy Research Center, National Institute of Infectious Diseases since July, 1997, as a part of administrative examinations (tests done by request of Ministry of Health, Labour and Welfare). These examinations include histopathology, serum antibody titers (anti-PGL-I antibody), PCR test and bioactivity of anti-bacterial agents.

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To develop the rapid and simple genomic diagnostic method, we analyzed the partial dnaA sequence of 27 mycobacterial species. The partial dnaA sequence could distinguish M. kansasii and M. gastri. Based on this region and RLEP sequence of M. leprae, we established the loop-mediated isothermal amplification method (LAMP) to detect each species. The LAMP method for M. kansasii and M. gastri, could detect 500 copies. Five copies of M. leprae genomic DNA could be detect in 30min. To simplify the sample processing, the LAMP assay was performed with FTA filter paper. M. leprae bacilli were applied on filter paper that lyses bacilli and bound DNA, eliminating sample centrifugation and extraction procedures. Assays of number standards showed reproducible detection rate 50 bacilli of M. leprae. Thus, The LAMP assay combined with FTA card has the advantages of rapid and simple detection and provides a practical, economical, and specific method for the diagnosis of M. leprae and NTM infection.

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Antibiotic susceptibility test of Mycobacterium leprae still relies on the time consuming methods based on the growth of M. leprae in the mouse footpad. Thus, the establishment of a rapid, simple and reliable method for the detection of drug-resistant M. leprae is one of the most urgent subjects in the treatment of leprosy patients. Recently, many data on the mutation of specific genes correlating with drug resistance have been accumulated. Application of these data permit the establishment of new gene diagnostic methods for drug susceptibility test of leprosy.
In this paper, the method using the low density oligonucleotide array that enables the detection of base substitutions involved in resistance against anti-leprosy drugs on a single platform was discussed. The low density oligonucleotide array described in this paper will open the new perspectives in terms of patient management for leprosy with low cost requirement.

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Host defense against Mycobacterium leprae (M. leprae) is chiefly conducted by cellular immunity. The adaptive immunity plays an important role, and T cells are activated through recognition of some immunodominant antigens of M. leprae. A search for an immunodominant antigen was carried out using human peripheral monocytes-derived dendritic cells and M. leprae-derived cell membrane fraction which is the most antigenic fraction of the bacteria, and Major Membrane Protein (MMP)-II was found as one of the immunodoninant antigens. The MMP-II highly stimulated both dendritic cells and macrophages to produce various cytokines. Further, MMP-II was recognized by T cells in vivo in patients infected with M. leprae. Then, we constructed a recombinant BCG secreting MMP-II. The recombinant BCG strongly stimulated both naïve CD4⁺ and naïve CD8⁺ T cells, and seemed to be a useful immunostimulatory agent.

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The most convenient way of diagnosing an infectious disease is by serological methods. To improve the quality of diagnosis in leprosy, simple tests in addition to diagnosis by clinical signs, are necessary. Here, PGL-I based methods for detection of multibacillary and paucibacillary leprosy, have been revisited and newer methods are discussed.

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[in Japanese]

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