(Vol.77 No.10 October 2002) <6> Kekkaku Vol.77, No.10:671-677,2002 Field Activities A STUDY ON PATIENTS WITH TUBERCULOSIS AMONG FOREIGNERS OVERSTAYED IN JAPAN AFTER EXPIRATION OF VISA -Activities over Three Years- Jumpei YAMAMURA and Takashi SAWADA Abstract An analysis of thirty-two cases of foreign patients with tuberculosis (TB) who had overstayed their residence permits was done at Minatomachi Medical Center over the past three years. The ratio of male to female patients was 2.5 to 1;the age of the subjects was evenly distributed. By country of origin, 87% of the cases were from Southeast Asia and East Asia. As none of the patients belonged to health insurance schemes because of their illegal status, their access to medical care was restricted, and the delay in visiting clinics was notable. As 22% of the cases were diagnosed as a result of programs to provide free TB screening for foreigners, it is important to ensure easy access to TB screening and medical facilities for early detection of TB. Amongst the cases, the proportion of cases of extrapulmonary tuberculosis occupied 28%, which is higher than that of Japanese. Although the defaulting rate among patients during the nine years period from 1990 to 1998 was high (41%), it decreased to 12% during the past three years of this study. The following active measure was vital for preventing defaulting from treatment and ensuring clinical cure: 1. Utilization of the Tuberculosis Prevention Law to reduce the economic burden of the patients. 2. Interpreters available in various native languages. 3. Provision of adequate information of TB before starting treatment. 4. Strict follow-up of patients to ensure coherence to treatment. 5. Establishment of an international network of governmental organizations, NGOs, and medical facilities to exchange informations on preventive and curative cares in the home and host countries. Key words:Tuberculosis, Foreigners without their residence permits, Default, Repatriation, International network Internal Medicine, Minatomachi Medical Center Correspondence to:Jumpei Yamamura, Internal Medicine, Minatomachi Medical Center, 7-6, Kinko-cho, Kanagawa-ku, Yokohama-shi, Kanagawa 221-0056 Japan. <7> Kekkaku Vol.77, No.10:679-686,2002 The 77th Annual Meeting Lunch Time Lecture TUBERCULOSIS CONTROL AND STRATEGY AS AN URBAN PROBLEM Toshio TAKATORIGE Abstract Tuberculosis is always an urban problem. There are differences in the severity of pulmonary tuberculosis in relation to socio-economic groups. The percentages of cases shown to be positive by smear microscopy of acid-fast bacilli in their sputum specimens and of cases with cavitary lesions in the lungs were high for the lower socio-economic group. The percentage of cases having had chest X-ray examination within the preceding year was low for the lower socio-economic group. The Osaka metropolitan area consists of many prefectures and cities. Osaka City is in the center of this great metropolis. Registered cases of each zone had statistically differences about social characteristics. This result was thought to reflect the population of each zone. Cooperative common political will against tuberculosis in this area is needed to promote tuberculosis control. We analyzed the incidence rate in Osaka City in five-year from 1978 to 1997. Until the first half of 1980, the tuberculosis incidence rate in Osaka City had been dropping every year, but the rate of decline has been slowed substantially or even stopped since 1983. The slowdown in the reduction of the tuberculosis incidence rate has occurred not in all wards, but in a few wards and it is a typical phenomenon of the middle-aged in those wards. Such tuberculosis among employees in an insecure position has a growing urban social problem. It is important to establish the cooperation between medical facilities and public health centers within the territory of tuberculosis hospitals in an urban area. The sources of tuberculosis infection in an urban area are quite diverse and complicated. We shall utilize a molecular epidemiologic analysis of the Mycobacterium tuberculosis. Key words:Tuberculosis control, Urban problem, Socio-economic, Political will Department of Social and Environmental Health, Osaka University Graduate School of Medicine Correspondence to:Toshio Takatorige, Department of Social and Environmental Health, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita-shi, Osaka 565-0871 Japan. (E-mail:tori@pbhel.med.osaka-u.ac.jp) <8> Kekkaku Vol.77, No.10:687-692,2002 The 77th Annual Meeting Education Lecture THE MECHANISM OF HIV REPLICATION AT THE SITE OF INFLAMMATION COINFECTED WITH HIV AND M.TUBERCULOSIS 1Koh NAKATA, 1Naoto KEICHO, 2Yoshihiro HONDA, 3Hideaki NAGAI, 3Akira HEBISAWA, and 4Akira FUJITA Abstract HIV-1 replication is remarkably augmented in macrophages at the site of inflammation due to tuberculosis. Reduction of expression of an inhibitory C/EBPƒÀ transcription factor and activation of NF-ƒÈ B are observed at the site of inflammation. Of 18 paraffin embedded tissue sections of HIV-tuberculosis confected autopsy or biopsy samples, 9 samples were positive for HIV-p24 staining, which were all derived from patients with blood CD4 cell counts more than 50/mm(3). Moreover, the P24 positive cells were morphologically macrophages or epithelioid cells. CD4 positive lymphocytes consistently located near the P24 positive macrophages. Therefore, we hypothesized that lymphocyte- macrophage contact is important for maximal HIV production from macrophages. In vitro experiments showed that contact between lymphocytes and macrophages reduced inhibitory C/EBPƒÀ, activated NF-ƒÈB and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBP/ƒÀ expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-ƒÈ B was activated. Antibodies which cross-linked macrophage expressed B-7, VCAM and CD40 were used mimic lymphocyte contact. Cross-linking antibodies abolished inhibitory C/EBPƒÀ expression; however, the HIV-1 LTR was not maximally stimulated and NF-ƒÈ B was not activated. Maximal HIV-1 LTR stimulation required both lymphocyte derived soluble factors and cross-linking of macrophage expressed co stimulatory molecules. These results demonstrate that neither contact nor soluble factor(s) are sufficient to maximally enhance HIV-1 LTR activity in macrophages. Contact between activated lymphocytes and macrophages is necessary to down-regulate inhibitory C/EBPƒÀ, thereby derepressing the HIV-1 LTR. Lymphocyte derived soluble factor(s) activate NF-ƒÈ B, further enhancing the HIV-LTR. Key words:HIV, Tuberculosis, C/EBPƒÀ, NF-ƒÈB, p24 1Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, 2Department of Medicine, Sendai Kosei Hospital, 3Department of Pulmonary Diseases, National Tokyo Hospital, 4Department of Pulmonary Diseases, Metropolitan Fuchu Hospital Correspondence to:Koh Nakata, Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655 Japan. (E-mail:knak@ri.imcj.go.jp) <9> Kekkaku Vol.77, No.10:693-697,2002 The 77th Annual Meeting Symposium TUBERCULOSIS IN ASIA Chairpersons:1Masashi SUCHI and 2Seiki TATENO Abstract 1.Philippines:The development, expansion and maintenance of pilot area activities: Cristina B. Giango(Technical Division, Cebu Provincial Health Office, the Philippines) In 1994, the Department of Health developed the new NTP policies based on WHO recommendations and started a pilot project in Cebu Province in collaboration with the Japan International Cooperation Agency. To test its feasibility and effectiveness, the new NTP policies were pre-tested in one city and one Rural Health Unit. The test showed a high rate of three sputum collection (90%), high positive rate (10%), and high cure rate (80%). Before the new guidelines were introduced, the new policy was briefed, a baseline survey of the facility was conducted, equipment was provided, and intensive training was given. Recording/Reporting forms and procedures were also developed to ensure accurate reporting. Supervision, an important activity to ensure effective per- formance, was institutionalized. Laboratory services were strengthened, and a quality- control system was introduced in 1995 to ensure the quality of the laboratory services. With the implementation of DOTS strategy, barangay health workers were trained as treatment partners. In partnership with the private sector, the TB Diagnostic Committee was organized to deliberate and assess sputum negative but X-ray positive cases. The implementation of the new NTP guidelines in Cebe Province has reached a satisfactory level, the cure rate and positive rate have increased, and laboratory services have improved. Because of its successful implementation, the new NTP guidelines are now being used nationwide. 2. Nepal:The DOTS Strategy in the area with hard geographic situation:Dirgh Singh Bam (National Tuberculosis Center, Nepal) Three groups of factors characterize the population of Nepal:1)Socio-cultural factors, e.g. migration, poverty, language;2)Environmental factors, e.g. geography and climate; and 3)Political factors, prisoners and refugee populations. These factors pose particular problems for implementing DOTS in various ways. Socio-cultural and environmental factors are particularly important in Nepal, and several measures have been developed to overcome these difficulties. One is active community participation through the DOTS committee. The committee consists of a group of motivated people, including social workers, political leaders, health services providers, journalists, teachers, students, representatives of local organizations, medical schools and colleges, industries, private practitioners, and TB patients. One DOTS committee is formed in every treatment center. A key role of the DOTS committee is to identify local problems and their solutions. It increases public awareness about TB and DOTS;supports people with TB in the community by providing treatment observers and tracing late patients;and encourages cooperation among health institutions, health workers, NGOs, and political leaders. The case finding rate is now 69%, and nearly 95% of diagnosed TB cases are being treated under DOTS. The treatment success rate of new smear-positive cases is nearly 90%. Thus, DOTS increases the case finding and treatment success. 3.Cambodia:HIV/TB and the health sector reform:Tan Eang Mao (National Center for Tuberculosis and Leprosy Control, Cambodia) Cambodia is one of the 23 high burden countries of tuberculosis in the world. Moreover, HIV/AIDS has been spreading rapidly since 1990s, which is worsening the tuberculosis epidemics. To cope with the burden, Cambodia has started implementation of DOTS in 1994 and has expanded it to most of public hospitals across the country by 1998. NTP of Cambodia is now enjoying high cure rate of more than 90%. However, due to the constraints such as weak infrastructure and the poverty, it is proved that many of TB sufferers do not have access to the TB services, resulting in still low case detection rate. It is for this reason that the NTP has decided to expand DOTS to health center and community level based on the new health system. Its pilot program that has been carried out in collaboration with JICA and WHO since 1999 has achieved promising results with high detection and cure rates. All of the over 900 health centers across the country will be involved in DOTS strategy by 2005. In the fight against TB/HIV, National Center for TB Control is providing free TB screening for PLWH (people living with HIV/AIDS), and it is developing a comprehensive plan of TB/HIV care including home delivery DOT services. 4.China:The World Bank Project and the Prevalence Survey in China:Hong Jin DuanMu (National Tuberculosis Control Center, China) Since 1992, China has utilized a World Bank loan to implement TB control projects among 560 million people in 13 provinces. Free diagnosis and treatment services have been provided to all patients, and a fully supervised standard short-course chemotherapy was applied to all diagnosed tuberculosis patients. In 1999, more than 190,000 smear-positive cases, ten times the number in 1992, were detected, and the registration rate of new cases reached 30 per 100,000 population. From 1992 to 1999, a total of 1.40 million smear- positive TB patients were discovered. The cure rate of smear-positive TB patients has been improved to an overall cure rate of 93.6%. The cure rates for the new cases and re-treatment patients were 95.1% and 89.6%, respectively. The fourth nationwide random survey for the epidemiology of tuberculosis was conducted in 2000. The prevalence of active tuberculosis was 367/100,000, the prevalence of infectious tuberculosis was 160/100,000, and the prevalence of smear-positive tuberculosis was 122/100,000. The tuberculosis mortality was 9.8/100,000. 5.Vietnam:The road to reaching the Global Target:Le Ba Tung(Pham Ngoc Thach Tuberculosis and Lung Disease Center, Vietnam) TB control activities started in 1957 and were reorganized in 1986 with the technical assistance of IUATLD, KNCV and material assistance of Medical Committee Netherlands Vietnam (MCNV). The New National TB Control Program follows the main directives of WHO and IUATLD's procedures of case-finding, chemotherapy and management. Passive case- findings are based on sputum smear. Chemotherapy with priority for smear positive cases is 3SHZ/6S2H2 for new cases and 3HRE/6H2R2E2 for retreated cases, which is undertaken with directly observed therapy (DOT strategy) mainly at commune health posts. Since 1989, DOTS strategy with 2SHRZ/6HE for new cases and 2SHRZE/1HRZE/5H3R3E3 for retreated cases has gradually been introduced in districts and communes of every province. In 1995, the government established the National and Provincial TB Control Steering Committees and has provided incentives for detected smear positive cases and cured smear positive cases. The government has also started strengthening the program of managerial and supervisory capacity for TB staff and has promoted the cooperation of all associated organizations of TB control. The WHO global surveillance and monitoring project reports that in 2000 Vietnam reached the global target, i.e., 99.8% population covered by DOTS with 80% of expected new smear positive cases being detected and a high cure rate ranging from 85.3% in 1989 to 90.3% in 1999. A distinguishing aspect of TB control in Vietnam is the effective international partnerships combined with high political commitment of the government nationally and provincially as well as active participation of all organizations in the community. Key words:Tuberculosis control, Asia, The DOTS strategy 1The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 2International Medical Center of Japan Correspondence to:Masashi Suchi, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (E-mail:suchi@jata.or.jp)