Objective: The present study was undertaken to evaluate the utility of the serodiagnosis of pulmonary tuberculosis and nontuberculous pulmonary mycobacteriosis by ELISA using a Pathozyme-Myco kit (Myco kit) and a Pathozyme-TB complex kit (TB kit) (OMEGA Diagnostics Ltd.).
Study population: The subjects comprised 256 healthy volunteers (HV, healthy hospital employees), 66 patients with sputum-positive active pulmonary tuberculosis (apTB), 14 patients with healed pulmonary tuberculosis (hp TB), 24 patients with nontuberculous pulmonary mycobacteriosis (NTM) and 32 patients with pulmonary diseases other than mycobacteriosis.
Results: 1) The serum IgG antibody titers determined with the Myco kit were significantly higher in the apTB group (p<0.01), the hp TB group (p<0.01), and the NTM group (p<0.01) than those in the HV and the other pulmonary disease group. At a cut-off value of the mean +2SD of the values obtained in the HV, the positive rate was 47.0% in patients with apTB, 50.0% in those with NTM, 21.4% in those with hp TB, 3.1% in those with other pulmonary diseases, and 1.6% in the HV. Analysis of ROC curves showed that the HV and the pulmonary mycobacteriosis group (apTB and NTM) were best distinguished by a cut-off value of -0.280 OD (log), with the sensitivity and the specificity being 83.3% and 78.5%, respectively. It was impossible to distinguish apTB from NTM. 2) The serum IgG antibody titers determined with the TB kit were significantly higher in the apTB group than those in the HV (p<0.01), the NTM group (p<0.05) and the other pulmonary disease group (p<0.01). No significant difference was observed between the HV and the patients with NTM or those with other pulmonary diseases. Although the positive rate of the test was low in the apTB group (42.4%), there was a significant difference between apTB and NTM (12.5%) (p<0.05), suggesting that apTB could be distinguished from NTM. 3) Since the serum antibody titers determined by the Myco kit showed no significant difference between apTB and NTM, and there was also no difference in the positivity between the two diseases, we performed serologic examination using the Myco kit to detect both diseases as pulmonary mycobacteriosis. After diagnosing pulmonary mycobacteriosis by the Myco kit, we then used the TB kit to separate apTB from NTM. In this case, the sensitivity and specificity of the test were 55.6% and 85.7%, respectively. Better methods should be developed to distinguish apTB from nontuberculous mycobacteriosis.

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The usefulness of the two tuberculin skin test in the preceding year for the contact investigation was reported, when a pulmonary tuberculosis patient was discovered in our hospital.
Four persons showed stronger reaction than the results in two-step tuberculin skin test in the preceding year after nosocomial infection.
One of them was diagnosed as pulmonary tuberculosis by chest radiograph, and antituberculosis chemotherapy was started. Other three started chemoprophylaxis. The chemoprophylaxis subjects might increase 4, if basic value of tuberculin reaction had not been available by two-step tuberculin skin test in the previous year. We could identify persons in whom tuberculin reaction became stronger by comparing the test results after exposure with the result of two-step tuberculin skin test in the preceding year. It is considered that two tuberculin skin test is very useful to efficiently execute the protective measure.

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A study was made on the relation between active pulmonary tuberculosis and underlying diseases in 119 tuberculosis patients.
Out of total 119 patients, 87 patients (73.1 %) had underlying diseases. The most common underlying disease was diabetes mellitus in 34 patients (39.1 %), followed by HCV (+) chronic hepatitis, sequela of cerebral infarction, hypertension and gastric ulcer. In patients who had underlying diseases, the mean age was higher, proportion of sputum smear positive cases was higher, albumin was lower, and period until sputum culture negative conversion was longer.
In patients who had diabetes mellitus, proportion of cases with cavity on chest X-P was higher, and in patients who had sequela of cerebral infarction or hypertension, mean age was higher.
In patients who had diabetes mellitus and whose HbA is was 9%, proportion of smear positive cases was higher, albumin was lower and period until culture negative conversion was longer than in patients who had diabetes mellitus and whose HbAlc was >9%, suggesting that control of blood sugar in diabetes mellitus related to severity of pulmonary tuberculosis. In patients who had diabetes mellitus and whose albumin was >3g/dl, period until culture negative conversion was longer than in patients who had diabetes mellitus and whose albumin was 3g/dl.
In patients who had underlying diseases, these diseases caused decline of tuberculous immunity and nutritional disturbance represented by lower albumin also promoted decline of tuberculous immunity. It is suggested that the underlying diseases affected the onset and progression of pulmonary tuberculosis.

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A 15-year-old girl, third-grade student of a junior high school (the index case) was found to have smear-positive, cavitary pulmonary tuberculosis. Contact investigation was conducted, including tuberculin skin test and chest X-ray examinations over 700 persons. Tuberculin skin test revealed an excess of strongly-positive reactors in the thirdgrade students. During 2 years after the detection of the index case, a total of 31 tuberculosis patients were newly diagnosed, and out of them 8 were culture positive and restriction fragment length polymorphism (RFLP) analysis of the 8 strains and that of the index case demonstrated an identical pattern. A delay in diagnosis of the index case and poor ventilation of the classrooms were attributable to this rather large outbreak. In addition the source case seems to be highly infectious, because transmission following only sporadic contact was documented.
Among the third-grade students and school staff, 129 persons were strongly-positive reactors to tuberculin skin test. Out of them one hundred five persons completed isoniazid chemoprophylaxis of recommended six months, and the others didn't receive chemoprophylaxis because most of them were aged above 30 years. All of them were followed up for 2 years after the detection of the index case, and out of 105 persons who received chemoprophylaxis, 2 cases (1.9%) were newly diagnosed as tuberculosis, while out of 24 persons without chemoprophylaxis, 6 cases (25 %) developed tuberculosis.

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Antituberculous treatment could be continued by using steroid as adjunctive therapy in two patients showing feabrile reaction to antituberculous drugs in spite of desensitization therapy.
Case 1 (39-year-old man) was admitted to our hospital with positive sputum-smear and bilateral cavitary tuberculosis (b II 2) on chest X-ray. He showed fever of 38-39°C after 8 days of HREZ treatment. Desensitization therapy of RFP with the combined use of prednisolone was enforced, since the exothermic reaction continued in spite of stopping the 4 medicines, and the treatment became possible. Case 2 (40-year-old woman) was admitted with positive sputum-smear and bilateral cavitary tuberculosis (b II 2) on chest Xray. The administration of drugs was stopped as temperature rose to 38-39 t after 12 days of HREZ treatment. Though the DLST of INH was positive, the treatment with INH became possible by the combined use of PSL.

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結核菌は初期の段階でエンドソームの成熟を停止させ抗菌作用に抵抗することでマクロファージ内での増殖を可能にする. T細胞は結核特異免疫の中心的なメディエーターであり, マクロファージを活性化することによって結核感染防御を誘導する。結核菌の蛋白抗原はMHCクラスII分子によってCD4T細胞に提示され, これを活性化しIFN-γ産生を誘導する. CD8T細胞もIFN-γを産生し, 細胞傷害活性を示すことで結核感染防御に重要である. 脂質抗原に対応するγδT細胞などのunconventionalT細胞はIFN-γ産生および細胞傷害活性を介して作用する.
結核感染は人類の約1/3にみられるが, 多くは感染がコントロールされ発病しない. 既に存在するBCGワクチンは成人においては適当な防御活性を賦与できないため十分ではない. 新たなワクチンを開発するためには, 何故BCGや自然感染が十分な感染防御活性を誘導できないか明らかにする必要がある. また, 結核菌のゲノム解読によって感染防御抗原や病原因子の解明に道を開いている. 防御抗原の同定はサブユニットワクチンの開発に重要であり, 病原因子の同定は全菌ワクチンのために重要である.
サブユニットワクチン開発には, (1) ワクチン抗原の免疫原性を高めるためのフォーミュレーション, (2) DNAワクチン, (3) リコンビナントワクチンに関する研究が含まれる. 有望なサブユニットワクチンには蛋白性アジュバントを用いたAg85やMtb8.4, あるいはAg85やESAT-6を含んだ融合蛋白, DNAワクチン候補にはHsp60, Ag85, Mtb8.4があげられる. 弱毒ワクチンとしては, (1) 病原遺伝子を欠失させた結核菌ワクチン, (2) 結核菌またはBCGの栄養要求性変異株, (3) cytolysinなどを組み入れて免疫原性を高めたリコンビナントBCG株, そして (4) Ag85のような重要な抗原を過剰発現させたリコンビナントBCG株の開発が考えられている. また, 異なったアプローチを組み合わせることで増強効果が期待できる. 例えば, 初回免疫を生菌, 追加免疫をサブユニットワクチンで, あるいは初回免疫をBCGと新たなワクチンを組み合わせることでワクチン効果を高めることができるかもしれない.
BCGワクチンや自然感染後の免疫応答に関する研究や低感受性および高感受性宿主問の比較検討から結核感染防御機構に関するわれわれの知見が蓄積されつつある. 有効なワクチン開発までまだまだ道のりは遠いが, 最近のゲノミクス, プロテオミクス, 免疫学研究によってBCGに勝る新たな結核ワクチンの登場する日が来ることを期待したい.

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