[Efficacy of the treatment for latent tuberculosis infection and delayed reactivation of tuberculosis].

PURPOSE: To evaluate the efficacy of treatment for latent tuberculosis infection and delayed reactivation of tuberculosis. METHOD: During a large tuberculosis outbreak, 129 individuals who were in close contact with tuberculosis patients and subsequently tested strongly positive by the tuberculin skin test were followed up for 10 years after identification of the source case. RESULT: Of the 129 individuals, 105 received treatment for latent tuberculosis infection for 6 months as per recommendation, while the remaining 24 did not receive treatment, because most of them were above 30 years of age and were therefore discouraged from receiving treatment, as was done in the earlier times in Japan. Of the 105 individuals, 5 (4.8%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 53 months. Of the 24 individuals who did not receive treatment for latent tuberculosis infection, 6 (25.0%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 8.2 months. CONCLUSION: The risk of active tuberculosis was reduced by 81.0% with treatment for latent tuberculosis infection, compared with that without treatment. Delayed reactivation of tuberculosis was observed among patients treated with isoniazid for latent tuberculosis infection for 6 months.

[Evaluation of tuberculosis transmission routes in an outbreak among young adults for developing an effective method for contact investigations].

PURPOSE: To evaluate the various transmission routes of tuberculosis in an outbreak among young adults in order to develop an effective method for contact investigations. METHOD: We reviewed the records of 21 tuberculosis patients involved in an outbreak of tuberculosis; the records were collected by conventional epidemiological studies. Mycobacterium tuberculosis isolates were genotyped using IS6110-based restriction fragment length polymorphism (RFLP). RESULT: The index patient was a 26-year-old man whose 32-year-old brother was identified as the source patient of tuberculosis through a contact investigation. Investigation of their contacts led to the identification of 10 tuberculosis patients. Further, 5 more patients with only casual contact with the index or source patients developed tuberculosis 18-25 months after identification of the index patient. The RFLP analysis of strains obtained from these 5 patients as well as the index and source patients revealed an identical pattern. Further, 4 persons, among those who had epidemiological links with some of the above-mentioned 5 patients, developed tuberculosis 22-34 months after identification of the index patient. All 21 patients were relatively young. In total, 15 strains obtained from these patients were sent for the RFLP analysis, all of which showed an identical pattern. The epidemiological links were categorized into a household environment, an entertainment area, a university, a music band, and a construction site. CONCLUSION: Molecular epidemiology can provide insights into the process of tuberculosis transmission, which may otherwise go unrecognized by conventional contact investigations. Additionally, it can play an important role in identifying places of tuberculosis outbreaks and routes of transmission in a contact investigation.

[The issue of tuberculosis in the elderly in Japan].

Tuberculosis in the elderly remains a health burden in Japan. Most of the elderly aged more than 70 years in Japan had become infected with Mycobacterium tuberculosis in their youth, and the elderly represent a population at a special high risk for developing tuberculosis owing to comorbidity and age-related immunosuppression. The characteristics of tuberculosis in the elderly are different from young patients. To reduce active tuberculosis in the elderly, treatment of latent tuberculosis infection for compromised host could be strengthened, however its impact might be limited. Elderly tuberculosis patients have not only clinical problems but also socioeconomic problems. Major problems of elderly tuberculosis patients are concurrent diseases, bed ridden states, necessity of nursing care, undernourished, poor adherence, and poor performance status of patients. With this symposium, we focused on the issue of tuberculosis in the elderly in Japan. The speakers were invited from various areas, including tuberculosis surveillance center, public health center and national hospital organization medical center. (1) Current trend of elderly TB: Masako OHMORI (Tuberculosis Surveillance Center, Research Institute of Tuberculosis, JATA) Although the tuberculosis (TB) incidence rate in Japan reached 19.4 per 100,000 in 2008, the rates among the elderly (65 + yrs) were high, e.g., 29.5 of those aged 64-74 years, 64.2 of those aged 75-84 years and 97.3 of those aged 85 years and over. The proportion of those aged 65 years and over increased from 36.8% in 1987 to 56.7% in 2008. Regarding the delay of case detection among elderly TB patients, the patient's delay tended to be shorter but the doctor's delay was longer. Although most TB patients including elderly TB patients were detected upon visiting a medical institution with some symptoms, in the case of elderly TB more patients were detected as outpatients or inpatients for a disease other than TB. Among TB patients aged 65 years and over, 26.4% died within one year. (2) The issues of elderly tuberculosis--An outbreak of pulmonary tuberculosis at nursing home for the elderly: Michiaki OKUMURA (Public Health Division, Public Health and Welfare Bureau, City of Osaka) I experienced a mass outbreak of pulmonary tuberculosis with 8 patients (including the source of infection) and 6 latent tuberculosis infections. Five patients (including the source) of the 8, I underwent restriction fragment length polymorphism (RFLP) analysis of isolated from the sputum. Five patients showed an identical RFLP pattern. These results showed that the infection had arisen from one source. The disease of 4 patients (aged 74-103) seemed to be caused by exogenous reinfections. The elderly tend to have some complications and to be malnutrition. These factors may be risk factors of tuberculosis reinfection for elderly. (3) The community DOTS in the elderly: Yoko HASHIMOTO (Wakayama Prefecture Gobo Health Center) In Wakayama prefecture, we have established a standard assessment list of adherence for tuberculosis patients. To identify predictors of default in the elderly, we investigated assessment lists of tuberculosis patients registered in Gobo Health Center from 2004 to 2007. Factors associated with default were concurrent diseases, side effects, disability and no family support. We have developed a liaison critical pathway for tuberculosis in Gobo Health Center and Tanabe Health Center since 2007. Introducing the path, we could strengthen community medical cooperation and build a network to support adherence. Health center staff should expand the community DOTS in the elderly with establishing an effective community collaboration. (4) The clinical issue of tuberculosis in the elderly: Takeshi KAWASAKI (Department of Respirology, Graduate School of Medicine, Chiba University, Department of Thoracic Disease, National Hospital Organization Chiba-East National Hospital) To identify the clinical issue of TB in the elderly, 139 cases were studied. There were 63 elderly cases in the 139. In the elderly TB patients, there were many cases of death and moving out, so the clinical results were poor. Some cases take much time to move out. It is important to inform doctors and people who care for the elderly that the elderly are under high risk of tuberculosis, to consider treatment for latent tuberculosis infection of high risk groups of tuberculosis, and that experts in tuberculosis, local doctors, health care center and geriatric facilities have close relation. (5) Problems and measures of tuberculosis in elderly group: Masahiro ABE (National Hospital Organization Ehime National Hospital) The percentage of the aged is high among all of tuberculosis patients, especially in the country compared to the city. I reported problems concerning tuberculosis treatment and ward management for elderly patients. During the hospitalization, the management of underlying diseases and new complications besides tuberculosis treatment is critical. Dysphagia features particularly make difficult to take anti-TB drugs and nutritional state worse. The rehabilitation of swallowing functions is effective to improve these conditions. To make discharge support more helpful, the support system, including regional cooperation path is expected to advance more widely and deeply.

[Research and control of relapse tuberculosis cases].

UNLABELLED: With this symposium, we focused on the relapse of tuberculosis in Japan. Out of 19,893 tuberculosis patients registered in 2007 in Japan, 7.48% were classified as relapse cases. Relapse cases have the risk of acquired drug resistance. But we have few analyses of the proportion of relapse tuberculosis cases with standard short course regimens for six months, factors contributing to tuberculosis relapse and the proportion of drug resistance among relapse TB cases in Japan. Therefore we analyzed the relapse tuberculosis cases in two rural areas and three urban areas. We also analyzed the proportion of drug resistance among relapse cases with the data of drug susceptibility survey of Ryoken. 1. Research of relapse tuberculosis cases: Makoto TOYOTA (Kochi City Public Health Center). To clarify the relapse rate and factors contributing to tuberculosis relapse, we investigated the relapse tuberculosis cases in the municipality where the proportion of elderly tuberculosis patients was high. Out of 902 tuberculosis patients registered in Kochi City Public Health Center during 10 years, 20 pulmonary tuberculosis patients were confirmed relapse cases with initial registered records. Pretreatment cavitations, sputum culture positivity at 2 months, medical miss-management (e.g. number of doses, duration of therapy) and poor adherence were considered to be factors contributing to tuberculosis relapse. Out of 20 relapse cases, 12 cases were detected with symptoms, while only 3 cases were detected by examination in law. 2. A clinical study on relapse cases of pulmonary tuberculosis: Shuichi TAKIKAWA (National Hospital Organization Nishibeppu National Hospital). The relapse of pulmonary tuberculosis was investigated. In the cases with a treatment history before short course chemotherapy, drug resistance rate was high, and thus it needs to be cautious of drug resistance at the time of the retreatment. In the cases with a treatment history of short course chemotherapy, relapse cases were recognized more significantly in male cases aged 70's. In the cases that deviated from the standard treatment and that became impossible to use rifampicin, it should be careful to emergence of isoniazid resistance. 3. The current status of the recurrence tuberculosis cases in Tokyo: Michiko NAGAMINE (Specific Disease Control Section, Tokyo Metropolitan Government Bureau of Social Welfare and Public Health). As for the background of the patient whose disease has relapsed, unstable elements are observed. After any symptom, more patients are diagnosed as a relapse case rather than finding by a medical check up. And more than half are related to homeless or life without fixed address. Their status of insurance is the livelihood protection, no insurance or the national health insurance. By RFLP analysis in Shinjuku city, some clusters have recurrent cases, one of clusters has both a relapse and exogenous reinfection. This is able to elucidate an infectious state. Like this, the analysis of each cluster can help effective countermeasures. 4. Recurrence of tuberculosis in the City of Yokohama between 2004 and 2008: Michihiko YOSHIDA (Shinagawa Public Health Center), Takahiro TOYOZAWA (Yokohama Public Health Center). To identify the TB recurrence rate, we studied a cohort of 40 cases (treatment completion 36 cases, interruption 4 cases) of whom had a previous history of TB treatment including isoniazid and rifampicin. The time for relapse was 7.9 +/- 8.6 years and the overall relapse rate was 0.6% (0.47-0.7%). Our study suggested the relapse was almost equal to the low incident countries but the long-term follow-up and surveillance data should be carefully evaluated. 5. Comparison of the retreatment cases of pulmonary tuberculosis: Yuka SASAKI (National Hospital Organization Chiba-East National Hospital). To investigate the factors of the retreatment of pulmonary tuberculosis, 134 retreatment cases were studied. The factors leading to retreatment were cavitary and large lesions in chest X-p, sputum smear positive and heavy alcohol-drinkers. The factors leading to defaulting of the treatment were lack in understanding of the treatment and their economic problems. Reexamination of the treatment and support of the patients are important to prevent the retreatment of the pulmonary tuberculosis. 6. Proportion of drug resistance among relapse tuberculosis cases, summary of Ryoken studies 1977-2002: Takashi YOSHIYAMA (Fukujuji Hospital). BACKGROUND AND OBJECTIVE: We have no historical analysis of the proportion of drug resistance among relapse TB cases. Therefore we would like to analyze the proportion of drug resistance among relapse cases in Japan. METHOD: Re-analysis of the data of drug susceptibility survey of Ryoken from 1977 to 2002. RESULT: The proportion of relapse cases among Ryoken has decreased in 1982-1987 and that proportion was 10% in 2002. The average age of relapse cases was 5 years older than the new cases and it was 66 years in 2002. The proportion of drug resistance among relapse cases has decreased form 39% (in 1977) to 16% (in 2002) for isoniazid, was stable and around 10% for rifampicin with 7.5% in 2002. The risk factors for drug resistance were younger age, foreigners and part time job. The proportion of drug resistance was higher among cases that were failure with previous treatment, then default with previous treatment and lower among cases with cure/completion at the previous treatment but this tendency was without significance.

Validity of using tuberculin skin test erythema measurement for contact investigation during a tuberculosis outbreak in schoolchildren previously vaccinated with BCG.

BACKGROUND: Few studies have examined the validity of administering tuberculosis control measures based on tuberculin skin test (TST) erythema measurement. The present study aimed to clarify the relationship between the erythema and the induration seen following TST and to evaluate the validity of diagnosing tuberculosis infection based on the erythema following TST in school-aged contacts who had been vaccinated with bacillus Calmette-Guérin (BCG) in infancy. METHODS: A 56-month longitudinal study from January 1999 through September 2003 followed 566 junior high school students in Kochi City who were contacts of an infectious tuberculosis case. To evaluate the diagnostic accuracy of the erythema and induration following TST of the contacts, false-positive and false-negative TST results were noted. RESULTS: The natural logarithm of the erythematous response size was linearly related to the induration size. When the size of the erythematous response was used to determine the presence of tuberculosis infection, the proportion of infected children increased with increasing exposure to the index case. When the TST results in the contact investigation were interpreted together with the change in the size of the erythematous response from that observed at the regular school-entry checkup, false positive test results were avoidable among the students who had a large erythematous response after the contact investigation TST, but whose response was only slightly larger than their erythematous response following the school-entry TST. Among the students whose TST results were negative, 1.9% developed tuberculosis. CONCLUSION: Both erythema and induration measurement were equally effective for identifying tuberculosis infection in schoolchildren vaccinated with BCG.

[Environmental factors relating to a mass outbreak of tuberculosis in a junior high school].

OBJECTIVE: To clarify environmental factors relating to a mass outbreak of tuberculosis. METHODS: A 15-year old girl, a third-grade student of a junior high school (the index case) was found to have smear-positive cavitary pulmonary tuberculosis. Among 718 subjects who underwent contacts investigation, the rates of infection and cases among different exposure groups were compared. The ventilation rate within the room of the junior high school was analyzed using sulfur hexafluoride (SF6) as the tracer gas. RESULTS: Up to 56 months after the detection of the index case, a total of 34 tuberculosis patients were newly diagnosed, and 155 persons were subjected to chemoprophylaxis. The rates of infection were 90.0% among homeroom classmates and 60.8% among other classmates, respectively. Out of the subjects who had only indirect contact with the index case, 11 patients were diagnosed. Most of the windows of the building were of the fixed sash type, permitting only low ventilation ranging from about 1.6 to 1.8 room air change per hour. When sliding doors of the room were opened, the SF6 concentration in the room was rapidly mixed up with that in the passage. CONCLUSION: Low ventilation of the room and overcrowding contributed to the high infection rate among homeroom classmates. Infectious droplet nuclei spread to the passage at recess. The homeroom of the index case was located in front of the building's entrance. The index case used some common rooms of the building. In addition to these environmental factors, other factors, especially the high infectiousness of the index case also contributed to the mass outbreak.