(Vol.74, No.6 June 1999) <1> Kekkaku Vol.74, No.6: 479-491,1999 IMMUNOTHERAPY FOR MDR-TB (MULTI-DRUG-RESISTANT TUBERCULOSIS)- ITS FEASIBILITY Izuo TSUYUGUCHI* MDR-TB is known to be man-made-disease. Inappropriate treatment of tuberculosis is responsible for the development of MDR-TB. MDR-TB is often accompanied with the immunosuppression of the host. Given that we are unable to develop another potent anti-TB drug in near future, immunotherapy di- rected at combating immunosuppression and enhancing the host's own immune response is an attractive approach to supplement conventional chemotherapy for MDR-TB. Patients with AIDS and patients with abnormalities of macrophage function have fre- quent problems with TB. This is suggesting that the host defenses involved in protection against mycobacteria include T-cell and monocyte/macrophage functions. That is cell-me- diated immunity. Diverse cytokines are known to play an important role in anti-TB cell-mediated immu- nity, including IL-2, IL-12, IL-18 and IFN-. Various animal experiments are indicatiog that administration of these cytokine(s) did recover the suppressed immunity and res- cued the host from death by tuberculous infection. However, we have to keep it in mind that the results obtained from animal model of mycobacterial infection on the study of pathogenesis and immune responses in TB is not always applicable to the understanding of human TB. Clinical trial of inhalation therapy with IFN- showed some improvement for drug-resistant TB. Cytokine treatment, however, often gave some deleterious side ef- fects such as high fever, malaise, general edema and even the death of the host. Clinical trials with M.vaccae have been extensively conducted by UK group. The mecha- nisms underlying its possible therapeutic action remain to be clarified, but when admin- istered at an appropriate dose, it has been shown to elicit a strong Th1 immune response. From the practical view point of immunotherapy for TB, surrogate markers of disease eradication and protective immunity are urgently required. Such markers would facilitate clinical trials by providing early evidence that test compounds or vaccines are effective. Even during the era when no potent chemotherapeutic agents were available, one third of the patients with TB survived the disease and enjoyed the entire lives, Then the ques- tion is what determines the alternative:survival or death following development of drug -resistant TB. Is it host immune responsiveness or virulence of the microbe, or both? Clearly much more work seems required before we are able to find some difinite means to conquer MDR-TB in human. Key words:MDR-TB, Immunotherapy, Cytokines *From the Osaka Prefectural Habikino Hospital, 3-7-1, Habikino, Habikino-shi, Osaka 583-8588 Japan. (Received 2 Dec. 1998/Accepted 8 Jan. 1999) <2> Kekkaku Vol.74, No6:493-497, 1999 THE FREQUENCY PROFILE OF TUBERCULIN SKIN TESTING AMONG STUDENTS IN NURSING SCHOOL Tadahiko Fujino*, Yoshiyuki ABE, Atsushi MIYATA and Kuninori SUZUKI The frequency profile of tuberculin skin testing (TST) among students in nursing school was studied. Students received a TST upon matriculation. The TST was done by the method of Mantoux, in which 0.1ml of PPDs was administered intradermally, and the di- ameters of skin rash and induration were read by the medical doctor at 48 hours. When TST results are negative-tahat is, the diameter of skin rashis below 10mm (in Japan, the TST results are judged by skin rash diameter rather than that of induration)-BCG vaccination is given. Those receiving the BCG vaccination are retested with a TST one year later. When the second TST was also negative both the BCG vaccination and TST were followed for two more years. Those students testing TST-negative are not permitted to take clinical training in the tuberculosis ward. Student's mean age on entrance was 18.6}2.1 years old. and all but three were female. About 70% of students entering in 1996 to 1998 had a history of previous BCG vaccina- tion. In 14% their positive TSTs could be attributed to probable infection with tuberculo- sis in childhood. In the remaining 16%, details as to TST and BCG vaccination status are unknown. The frequency distribution of TST results was bimodal, showing one peak at 6mm and another at 12mm (skin rash diameter). The percentage of negative and positive reactors are 47.1% and 52.9%, respectively. The TST-negative students entering in 1994 to 1996 were given the BCG vaccination. Twenty-four of 134 students (17.9%) ramained negative at the second TST, and 6 stu- dents (4.5%) at the third year, even after two repeated BCG vaccinations. The TST results were chronologically observed in the above 6 students after BCG vac- cination. The TST results of two students showed positive in September, 1996 and June, 1997. While four students showed positive in September, 1996, all ultimately reverted to negative when retested in June, 1997. Those students had negative results for TST at the initial test in 1998 had the two step-tu- berculin skin testing. All eight students with negative TST had the history of BCG vaccination. The second TST showed positive except one student whose scar after BCG vaccination was not observed on the arm. The TST is currently recommended in hospital tuberculosis-control programs. If TST- negative, medical staff and students may not work in the tuberculosis ward. However, after BCG vaccinations is given, and subsequent TST conversion is confirmed, they are then able to work or to have training in the ward. From our results there is 4.5% non- convertors even after 2 years of repeated BCG vaccinations. Howerer, these non-convert- ers turned positive four months after BCG vaccination, only to revert to negative nine months later. These students are considered to have delayed hypersensitivity to PPD after BCG vaccination. However, their reactivity waned in the short period of nine months after the conversion of their TST's. Therefore, it is concluded that non-converters after repeated BCG vaccinations are able to have clinical training in the tuberculosis ward ad long as their BCG vaccinations are correctly administered and any immunological deficiencies are ruled out. Key words:Tuberculin skin testing, Twostep tuberculin test, BCG vaccination, Non-converter, Students in nursing school *From the Respiratory Division, National Sanatorium Kanagawa Hospital, 661-1 Ochiai, Hadano-shi, Kanagawa 257-8585 Japan. (Received 16 Sep. 1998/Accepted 14 Jan. 1999) <3> Kekkaku Vol.74, No.6:499-505, 1999 SERUM SOLUBLE INTERLEUKIN-2 RECEPTOR IN PATIENTS WITH PULMONARY MYCOBACTERIAL DISEASES Atsuhiko TADA*, Shin KAWAHARA, Naokatsu HORITA, Akihide HORIBA, Akihiko TAMAOKI, Chiharu OKADA, Yasuo MISHIMA, Ryo SODA, and Kiyoshi TAKAHASHI Serum soluble interleukin-2 receptor (sIL-2R) levels were measured in patients with untreated pulmonary tuberculosis (24 cases), patients with multidrug-resistant intracta- ble pulmonary tuberculosis (7 cases) and patients with pulmonary non-tuberculosis myco- bacteriosis (27 cases). Serum sIL-2R levels were elevated in patients with pulmonary mycobacterial diseases and were elevated in untreated pulmonary tuberculosis patients than in other patients. In patients with new tuberculosis, serum sIL-2R levels were higher in patients with exten- sive lesions. Serum sIL-2R level showed significant positive correlation with serum C-re- active protein level and erythrocyte sedimentation rate, and significant negative correlation with serum albumin level. In patients with intractable tuberculosis and pa- tients with non-tuberculous mycobacteriosis, serum sIL-2R levels were lower than in pa- tients with new tuberculosis, Even in patients with extensive lesions, serum sIL-2R levels were not elevated. Lower levels of serum sIL-2R, marker of immunocompetent cell activity, suggested that immunocompetent cell activity was suppressed in intractable tuberculosis and in non- tuberculous mycobacteriosis. Key words:Solble interleukin-2 receptor, Tuberculosis, Multidrug-resistant intractable tuberculosis, Non-tuberculous mycobacteriosis *From the Department of Internal Medicine, National Minami- Okayama Hospital, 4066, Hayashima, Hayashima-cho, Okayama 701-0304 Japan. (Received 5 Nov. 1998/Accepted 4 Feb. 1999) <4> Kekkaku Vol.74, No.6:507-511, 1999 TUBERCULOSIS MICROEPIDEMIC IN A COMMUTER BUS Takenori YAGI*, Yuka SASAKI, Fumio YAMAGASHI, Fumio MIZUTANI, Akihiko WADA, and Fuminobu KURODA A tuberculosis microepidemic in a commuter bus was reported. Index patient was a 22 -year-old woman who was an employee of an electronic company. An abnormal shadow was found on her chest roentgenogram during an annual medical check-up in June, 1996. As her sputum smear was Gaffky 6, she was admitted to our hospital for medication. Extraordinary examinations including PPD skin test and chest X-ray were carried out on 49 employees of the company in October, 1996. As the result of these examinations, the distribution of maximum diameters of erythema in PPD skin test showed bimodal distri- bution, and tuberculosis was discovered in two patients by Chest X-ray examination. Moreover, preventive administraiotn of Isonicotinic acid hydrazide (INH) was indicated for 3 employees based on very strong skin reaction to PPD. These five employees were working separately from the index patient and had little contact with the patient in the work places, but using a same commuter bus. Therefore, we strongly suspect that they were infected from the index patient not in the work place but in the commuter bus. The air-conditioning of the bus used a closed recirculation system, hence insufficient ven- tilation in the bus contributed to the spread of tuberculosis infection. Key words:Pulmonary tuberculosis, Outbreak, Microepidemic, Extraordinary examination, Closed environment, Ventilation *From the Division of Thoracic Disease, National Chiba-Higashi Hospital, 673 Nitona-cho, Chuo-ku, Chiba 260-8712 Japan. (Received 11 Dec. 1998/Accepted 10 Feb. 1999) <5> Kekkaku Vol.74, No.6:513-517, 1999 ONE CASE OF CHRONIC PYOTHORAX WITH MRSA INFECTION CURED BY AIR-PLOMBAG METHOD Tokuro OTSUKA*, Yoshio IMURA, Huroshi YAMAMOTO, and Susumu SASANO It is very difiicult to cure a chronic pyothorax with MRSA infection. We experienced one such case with low pulmonary function (VC 1700ml, %VC 50.7%), 73 years old man, who had a history of esophageal cancer and was operated two years ago. As the control of bacteria and the surgical intervention are both important in the treatment of pyothorax cases, we tried to reduce MRSA by washing with Povidone-Io- dine solution through the drain. Then, we selected Air-plombage method as it is expected to maintain or to increase the pulmonary function after operation. We could easily close the bronchial fistula with a muscle flap, as it was located at the centre of the cavity. During the operation we frequently used acidic electrolyzed NaCl so- lution against MRSA. For one month after the operation, we used Vancomycin which is effective against MRSA, however, rather severe side effects were seen, and finally and MRSA vanished. Pulmonary function has improved from the initial VC 1700ml, %VC 50.7% to VC 2120ml, %VC 63.6% one year later. We recommend Air-plombage method for such cases with low pulmonary function under the control of MRSA by using acidic solution. Key words:Chronic pyothorax, MRSA, Air-plombage *From the Thoracic Surjery,Tokyo Metropolitan Fuchu Hos- Pital, 2-9-2, Musashidai, Fuchu, Tokyo 183-0042 Japan. (Received 2 Nov. 1998/Accepted 14 Jan. 1999) <6> Kekkaku Vol.74, No.6:519-521, 1999 A CASE OF ACTIVE PULMONARY TUBERCULOSIS IN THE RIGHT LOWER LUNG FIELD DETECTED BY CT Yasuhito HONDA* Many studies have indicated the pitfalls in detecting abnormalities on chest radiogra- phy, although radiography of the chest has been used for the screening of peripheral lung cancer. Recently, mass screening with a spiral computed tomography scanner has been performed for the detection of small peripheral lung cancers, and it has been clarified that spiral CT was superior to chest radiography in the screening and detection of periph- eral lung cancer. However, there have been only a few reports on pulmonary tuberculosis that was detected by chest CT. We report a case of active pulmonary tuberculosis de- tected by chesst CT, and invisible on plain chest radiography. 39 year old female consulted our hospital, because chest rediography at mass screening for lung cancer showed an abnormal shadow in the left upper lung field. Chest CT re- vealed a high density nodule with calcification compatible with old tuberculosis. How- ever, there was another 20mmX10mm sized nodule in right S9b that was invisible on plain chest radiography. The nodule had a clear margin with satellite lesion that charac- terize active pulmonary tuberculosis. Bronchial lavage was performed by broncho- fiberscopy, and Mycobacterium tuberculosis was isolated from lavage fluid. The nodular shadow disappeared after the treatment with isoniazid and rifampicin for 9 months. Key words:Pulmonary tuberculosis, Chest CT *From the Department of Respirology, NTT Sapporo Hospital, South 1, West 15, Chuo-ku, Sapporo 060- 0061 Japan. (Received 21 Dec. 1998/Accepted 10 Feb. 1999)