When Mycobacterium tuberculosis infects humans, about 20% of those infected actually develop tuberculosis (TB)1). In Japan, the incidence of TB in 2008 was 24,760 cases (19.4/100,000 persons) and the rate has been decreasing gradually, but is still higher than in the USA, Holland, and Belgium, for example. Histologically, tuberculosis displays exudative inflammation, proliferative inflammation and productive inflammation depending on the time course. In productive inflammation, granulomatous lesions with necrotic centers are formed. The typical granulomas consist of epithelioid macrophages, Langhans' multinucleated giant cells, lymphocytes and fibroblasts, and the process of their formation involves many cytokines, chemokines and transcription factors. These findings have been derived primarily from animal experiments utilizing an airborne infection apparatus. The conditions for airborne infection have been described in detail elsewhere2). This mini-review focuses on what has been found through animal experiments, and also indicates areas for which data are not currently available.
The role of vaccines to tuberculosis and leprosy is to induce a cellular immunity, and as a result to induce the differentiation of memory CD8+ cytotoxic T cells. 'Help' from CD4+ T cells is important for the differentiation of naive CD8+ T cells to effector and memory CD8+ cytotoxic T cells. However, how CD4+ T cell 'help' is involved in the steps instructing T helper (Th) polarization is not yet clear. Peptide-25, a major Th epitope of Ag85B from Mycobacterium tuberculosis , preferentially induced development of Th1 cells. In contrast, altered peptide ligands (APL) that have a substitution of glycine for alanine at position 248 of Peptide-25 induced solely Th2 development. To elucidate the role of Th polarization on the 'Help' function of CD4+ T cells, we established an in vitro culture system using OVA specific CD8+ T cells, Peptide-25 specific CD4+ T cells and splenic dendritic cells (DCs). The DCs that were pre-cultured with Peptide-25 specific CD4+ T cells together with OVA and Peptide-25 induced the proliferation and granzyme B production of OVA specific CD8+ T cells. On the other hand, the DCs that were pre-cultured with Peptide-25 specific CD4+ T cells together with OVA and APL induced only proliferation of OVA specific CD8+ T cells. These results suggest that Th1 immune response induced by Peptide-25 plays an important role in the induction of functional activation of CD8+ cytotoxic T cells.
Prevalence of disability among leprosy patients and effectiveness of standard predonisolone treatment for leprosy reaction at field level in some place of Myanmar are shown in this paper as results of joint leprosy research collaboration. WHO disability grading was measured for all newly registered leprosy patients through 2007 in 5 selected townships of Ayeyarwaddy Division, with the results of G0=66.3%, GI=18.9%, GII=14.7%(N=95). The cross-sectional disability survey at selected 9 townships in Mandalay, Sagaing and Magway Division for all registered patients who had completed WHO/MDT done by JICA project in 2003/4 showed G0=62.5%, GI=2.4%, GII=35.1% (N=10,528). From these two data, it is supposed that considerable number of patients with G1 at registered time developed worsening of disability from G1 to G2. Proportion of G0 also reduced a little bit in patients who completed WHO/MDT. Early detection and proper treatment of leprosy reaction are one of the main issues of prevention of disability. Effectiveness of leprosy reaction services were evaluated at Mandalay Special Skin Clinic, where WHO fixed regimen of prednisolone were given as routine service. 100 cases were evaluated who developed leprosy reactions from 1st December 2007 to 31st December 2008 and identified severe reaction who needed oral prednisolone treatment. Evaluation criteria of "effective" was defined as "no more signs and symptoms of reactions were present after treatment. And "less effective" was defined as "more than one of signs and symptoms were still remained after treatment". Over all "effective" was 36(36%) and "less effective" was 64(64%). It was also found that rates of improvement of nerve functions, either in sensory or in motor, were little after the standard treatment.
Macrophages (MΦs) play a central role as anti-microbial effector cells in the expression of host resistance to mycobacterial infections. With respect to antimicrobial effector molecules of host MΦ against mycobacterial pathogens, recent studies suggest the possibility that the reactive nitrogen intermediates (RNI) - and reactive oxygen intermediates-independent antimycobacterial mechanism(s) may be crucial for the antimycobacterial function of host MΦ. In this context, we previously found that free fatty acids (FFAs) such as arachidonic acid (AA) and linolenic acid exhibited potent antimicrobial activity against mycobacterial organisms, including Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC). In addition, FFAs in combination with RNI played critical roles in manifestation of the activity of MΦ against mycobacterial organisms. Moreover, our recent studies have shown the following findings. First, anti-MTB activity of IFN-γ-activated MΦs was specifically blocked by arachidonyl trifluoromethylketone (aTFMK), an inhibitor of cytosolic phospholipase A2 (cPLA2). Second, ATP potentiated the anti-MAC bactericidal activity of MΦs cultivated in the presence of clarithromycin and rifamycin. This effect of ATP was closely related to intracellular Ca2+ mobilization and was specifically blocked by aTFMK. Third, intramacrophage translocation of membranous AA molecules to MAC-containing phagosomes was also specifically blocked by aTFMK. In the confocal microscopic observation of MAC-infected MΦs, ATP enhanced the intracellular translocation of cPLA2 into MAC-containing phagosomes. These findings suggest that FFAs (especially AA) produced by the enzymatic action of cPLA2 play important roles as antimycobacterial effectors in the expression of MΦ antimicrobial activity against mycobacterial pathogens.
The number of ex-leprosy patients has reduced rapidly who were forced to be admitted under leprosy prevention/segregation law and are staying at national sanatoriums with different disabilities due to different physical and social reasons for long time in Japan. Most of them have been of clinically cured status for decades after effective chemotherapy. Some have still been suffering from acute or chronic neuralgic pains which are supposed to be long standing consequences of nerve damage of leprosy and getting medications for long period. Pharmacy department of National Suruga Sanatorium has studied the amount of prescriptions of some medicines for last 11 years, which were thought to be prescribed for pain including neuralgic pain. There seem to be some tendencies of medications during last decade. VitaminB12 (Mecobalamine) is one of the commonest drugs for neuralgic pain at this sanatorium and the amount of prescription had almost been unchanged through the years. Prescription of non-steroid antiinflammatory drugs (NSAIDs) increased year by year, which may reflect the increasing age of ex-patients who need more pain killers for their painful joints or back. Loxoprofen is the most popular pain killer here and increased by ten times for last decade. The number of prescription for Pentazocine and Hydroxyzine Hydrochloride injection increased for last several years, which reflects a few patients who were still suffering from severe chronic neuralgia for years. It is desirable that a standard regimen for chronic neuralgic pain as a consequence of nerve impairment in leprosy will be developed as soon as possible.