One of the unique features characterizing human tuberculosis (TB) is its pathogenesis. The pathogenesis of TB involves cell-mediated immune responses against Mycobacterium tuberculosis. Concisely, macrophages activated by various soluble mediators or cytokines released through the cellular interactions after infection with M. tuberculosis play a pivotal role in the pathogenesis of human TB. In fact, very complex cellular interactions are going on within the host after infection with or endogenous reactivation of M. tuberculosis. Cells communicate by cell-cell contact and by the release of mediators which may originate locally, called cytokines.
In TB infection, macrophages can be activated by two ways directly with mycobac terial organisms or lipid fractions of their cell walls at the earlier phase of infection, and indirectly with cytokines produced by CD4⁺ T cells specifically activated by mycobacterial peptide antigens at the later phase of infection. The various clinical features of TB are the summarized outcome of cell to cell interactions mediated by diverse cytokines produced by various immune cells which are initially triggered by M. tuberculosis infection.
CD4⁺ T cells can be classified into two subsets according to the patterns of cytokines they produce Thl cells give rise to cell-mediated immunity and are characterized by the production of IL-2 and IFN-γ, whereas Th2 cells are more efficient in mediating antibody production and secrete IL-4, IL-5, IL-6 and IL-10. Th2 cells can control Thl cells and vice versa. Th2 cells therefore inhibit the production of cytokines by Thl cells by releasing IL-4 and IL-10.
Infection with mycobacteria stimulates macrophage IL-12 production which appears to act directly on naive CD4+ T cells to induce Thl development and initiation of cell-mediated immunity. IL-12 is a critical component in the development of cell-mediated immunity. In addition, IL-12 also activates NK cells and γ/δ T cells, both of which secrete various macrophage-activating factors to kill M. tuberculosis.
One of the structural characteristics of M. tuberculosis is the cell wall rich in lipid components. Of importance among various biological activities of the cell wall lipids is the stimulation of mononuclear phagocytes to produce a certain number of cytokines or monokines including IL-12 and IL-10, both of.which play important roles in regulation of immune responses in mycobacterial infection and in pathogenesis of TB. Considering the biological characteristics of mycobacterial lipid components, we need take these lipids into consideration in the future research of TB immunology, particularly in the strategy for development of a potent TB vaccine

View full abstract

A twenty-four year old male Peruvian of Japanese origin, who came to Japan in September 1990 and had been working in a minor factory in a rural area, was admitted to a hospital in March '91 with severe cough. Smear examination of his sputum smear was positive for acid-fast bacilli and his chest X-ray showed multiple cavities (Index case). Subsequent contact examination identified further four patients with pulmonary tuber culosis among his colleagues in the factory, all of whom lived in the same house with the index case.
During following three years, further six patients with mycobacteriosis, two Peruvians and four Japanese, were found among the employee of that factory. M. tuberculosis was cultured from the sputa obtained from seven of these eleven patients. Another patient was diagnosed as non-tuberculous mycobacteriosis.
Restriction fragment length polymorphism (RFLP) analysis carried out with five strains of M. tuberculosis isolated from these patients revealed the identical RFLP pattern which is uncommon in Japan. Still more, an isolate from another patient was subjected to RFLP analysis by chance, and was found to show the same RFLP pattern. Later epidemiological study revealed that the last patient, a 53 year-old saleswoman of boxlunch, might have some contact with the index case at her booth.
Though RFLP analysis was not done for the isolate from the index case, from the identity of RFLP patterns of other isolates, clinical course and epidemiological study, it is considered that six patients were certainly, and two others were probably infected from the index case. One of the patients had a history of surgical treatment for pulmonary tuberculosis and, as RFLP analysis could not be carried out, it is not possible to determine whether his disease was due to reactivation or re-infection.
Tuberculin skin test survey of 133 workers in the factory was carried out in March '91. The diameter of erythema showed bimodal distribution pattern for the Japanese workers. Considering that most of the young Japanese have been vaccinated with BCG, it is assumed that at least 40% (10/23) of Japanese workers younger than thirty years old were infected in this epidemic. All the Peruvians, who had not been vaccinated with BCG, showed positive reaction to PPD (mean diameter was 41.9mm) and were assumed to had been infected newly in this epidemics or in the past. Chemoprophylaxis were indicated for two young Peruvians only. Subsequent patients were diagnosed among the strong tuberculin reactors (For Japanese ≥50 mm, for Peruvians ≥30mm in diameter).
Total delay in the diagnosis of the index case was considered to be about six months. Though he was coughing on his entrance to Japan on September '90, no reliable medical checkup was done until he was pointed out the abnormal findings on his chest X-ray image at a routine medical checkup in November '90. At that time he was recommended to go to some hospital or clinics, but he did not obey this recommendation promptly. Such a delay may cause this outbreak.

View full abstract

A 54 year-old woman was admitted with cough and high fever. Computed tomographic scan of the chest showed bilateral patchy infiltrates, predominantly in the upper lobes. Eosinophils in the bronchoalveolar lavage fluid (BALF) accounted for 19% of BALF cells. Furthermore, Mycobacterium avium was isolated from a bronchial washing from the upper area of the right lung (S³) and a sample of sputum which had been submitted for microbial examination about 1 month before admission by another clinic. Based on these finding's the diagnosis of eosinophilic pneumonia associated with Mycobacterium avium infection was established. The infiltrates of the lung rapidly decreased after administration of anti tuberculous agents.
The simultaneous presentation of eosinophilic pneumonia and Mycobacterium avium infection has not been previously reported. Because of the efficacy of antituberculous agents in this case, we concluded that Mycobacterium avium was a cause of eosinophilic pneumonia.

View full abstract

Many leprosy patients have deformity or disability owing to the characteristics of Mycobacterium leprae i.e. M. leprae affects skin and peripheral nerve. Optimum growth temperatue of M. leprae was estimated by clinical manifestations and animal experiments, and it was concluded that the optimum temperature is 33°C, and this characteristic of M. leprae may be one of the reason why M. leprae affects skin tissue.
There was no reliable treatment of leprosy before 1943, but effectiveness of promin againt leprosy was proven in 1943, and chemotherapy of leprosy was gradually improved especially since 1960 after the discovery of mouse footpad inoculation of M. leprae.
In vitro cultivation technique of M. leprae is still unestablished, but susceptibility of ninebanded armadillo to M. leprae was discovered in 1970. Supply of M. leprae collected and purified from M. leprae infected armadillo tissue became available, then biochemistry, immunology and molecular biology of M. leprae was improved significantly.
Ridley-Joppling's classification of leprosy i.e. two types (tuberculoid and lepromatous) and two groups (indeterminate and borderline) classification is being adopted at present.
Rifampicin, DDS (dapsone) and clofazimine (lamprene) are widely used for chemo therapy of leprosy. WHO is recommending Multidrug Therapy (MDT) of leprosy i.e. administration of rifampicin and DDS for paucibacillary group, administration of rifampicin, DDS and clofazimine for multibacillary group.
About 2.4 million leprosy patients are registered and under chemotherapy in the world at present, and about five hundred thousand new patients are being registered every year. Target of leprosy elimination by WHO is prevalence rate of leprosy should be less than one per ten thousand in every country. If all registered cases and all newly found cases can be covered by MDT, leprosy will be eliminated by the year 2000.

View full abstract