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PubMed2002

[Frequency of previous tuberculosis history in patients with and without active tuberculosis admitted to our hospital in 1980-83 and in 1997-99].

To study recurrence rate over a long period after recovery from previous tuberculosis history, we examined the frequency of previous tuberculosis history in patients who were admitted to our hospital in 1980-83 and in 1997-99 and the comparison was made between cases with and without culture-positive tuberculosis. The tuberculosis groups comprised of 297 patients in 1980-83 and 688 patients in 1997-99. The non-tuberculosis groups (control groups) comprised of 373 patients in 1980-83 and 1092 patients in 1997-99 with non-tuberculosis diseases other than the tuberculosis-related diseases such as non-tuberculosis mycobacteriosis, pulmonary aspergillosis, bronchiectasis, chronic bronchitis and tuberculosis sequelae. The patients with viral chronic hepatitis previously operated and transfused were also excluded as they might be operated because of pulmonary tuberculosis in the era of surgical treatment for tuberculosis. In both tuberculosis and control groups, they had previous tuberculosis history most frequently when they were twenties. In the control groups, the frequency of previous tuberculosis history among cases admitted in 1980-83 and were born in 1910-19, 20-29, 30-39, 40-49 were 15/84 (17.9%), 22/93 (23.7%), 11/77 (14.3%) and 3/43 (7.0%), respectively, and those admitted in 1997-99 were 11/70 (15.7%), 30/231 (13.0%), 28/288 (9.7%), and 10/230 (4.3%), respectively. In these 4 birth year groups, frequency of previous tuberculosis history among cases admitted in 1997-99 were significantly lower than that admitted in 1980-83 (p < 0.05, one-sided paired t-test), and the fact suggests that persons with tuberculosis history died earlier than those without it. In the tuberculosis groups, the frequencies of previous tuberculosis history among cases admitted in 1980-83 and were born in 1910-19, 20-29, 30-39 and 40-49 were 20/35 (57.1%), 31/58 (53.4%), 19/48 (39.6%), and 11/53 (20.8%), respectively, and those among cases admitted in 1997-99 were 30/99 (30.3%), 58/125 (46.4%), 22/102 (21.6%) and 17/136 (12.5%), respectively. The frequency of previous tuberculosis history among cases admitted in 1997-99 was significantly lower than that admitted in 1980-83 (p < 0.01) as was the case in the control groups. As recurrence within 5 years had occurred in only 4 out of 113 tuberculosis patients (3.5%) in the above-mentioned 4 birth year groups, almost all tuberculosis patients were assumed to have recovered completely from previous tuberculosis. Comparison between the recurrence rate from previous tuberculosis and the incidence rate from the remotely infected persons without previous tuberculosis history in the same birth year group can be done by calculating the prevalence of tuberculosis infection for each birth year group using a model of annual risk of tuberculosis infection appropriate for Japanese. The ratios between the recurrence rate from previous tuberculosis patients and the incidence rate from remotely infected persons without previous tuberculosis history were 4.71, 2.33, 1.78 and 1.11 in 1980-83 and 1.84, 3.99, 1.80 and 1.11 in 1997-99 for groups born in 1910-19, 20-29, 30-39 and 40-49, respectively. The ratio did not change systematically with time in these groups, indicating the recurrence rate did not change with time more than ten years after recovery from previous tuberculosis. The ratio was about 3 for groups born in 1910-19 and 20-29 and 1 for group born in 1940-49. Almost all patients born in 1940-49 could receive chemotherapy for tuberculosis in their twenties, while most of the patients born in 1910-29 could not. Therefore, the above-mentioned fact may reflect the recurrence rate of patients treated successfully with chemotherapy is almost the same as the incidence rate from remotely infected persons, while that the recurrence rate from previous tuberculosis patients spontaneously recovered is 3 times higher than the incidence rate from remotely infected persons.

Adolescent↗
PubMed2005

[Amendment of tuberculosis prevention law and prospect of tuberculosis control program].

Tuberculosis Control Law, which provides a legal basis for national tuberculosis control, was amended in 2004 and entered into force on April 1, 2005. As it is more than half a century since its initial enactment, the law has been drastically amended based on some of the relatively new important ideas such as up-to-date scientific evidence, recent epidemiological conditions of tuberculosis, decentralization and respect for human rights. Japan has once seen a time when considerable part of producing population were affected with tuberculosis which caused severe infliction on the whole Japanese society including economical damage. With progress in medical technology such as development of chemotherapy and improvement of sanitary conditions, there was a major decline in incidence rate and death rate during the 1960s and 1970s. However, the decrease in TB incidence began to stagnate in the 1980s, partly explained by aging of the overall society and worsening of the urban tuberculosis conditions. Since then, there has been a discussion on review of national tuberculosis control program, and the increase in the number of tuberculosis patients in 1997, which happened for the first time in 38 years, precipitated the process. In 1999, 'Tuberculosis Emergency Declaration' was announced by the Minister of Health, which led to emergency national tuberculosis survey in 2000, and based on the result came forward the Recommendation on Comprehensive Review of National Tuberculosis Plan. Main ideas and spirits of the Recommendation were taken full account of during the process of the amendment of the law and were mostly reflected on the final outcome. Five key elements include; Establishment of National Tuberculosis Fundamental Guideline and Prefectural Tuberculosis Prevention Plan, Review on TB screening, Review on BCG vaccination policy, Promotion of a Japanese version of DOTS, Review on Tuberculosis Advisory Committee 1. Establishment of National Tuberculosis Fundamental Guideline and Prefectural Tuberculosis Prevention Plan With a view to establishing a comprehensive plan in the context of local tuberculosis situation, it was deemed to be necessary for both the central government and local governments to set out a detailed and comprehensive plan that may supplement the newly amended law. Prior to the amendment of Tuberculosis Prevention Law, it was made obligatory in the amended Infectious Diseases Control Law for the central government to establish National Fundamental Guideline and for local governments to establish Prefectural Prevention Plan. 2. Review on TB Screening With a view to promoting early detection of tuberculosis, tuberculosis screening system was totally reviewed to be turned into more effective and efficacious means for the purpose. Previously, all people above 19 years of age were to be screened annually for tuberculosis with chest X-ray. By this means, however, only 1,600 tuberculosis patients were detected out of 20,000,000 people screened which means the detection rate is 0.0067%. Thorough analysis was made to identify who would benefit from regular X-ray screening in terms of detection of tuberculosis patients and was decided to be those who have certain risk factors to develop tuberculosis such as the elderly and socio-economically challenged people and those who, once develops tuberculosis, may easily infect others such as school teachers, healthcare workers and such. Also the procedure of contact trace was reviewed and in highly required cases, compulsory examination implemented by health care officers has become a choice. 3. Review on BCG vaccination policy Previously national BCG policy included BCG vaccination for young children who tested negative on tuberculin skin test before they become 4 years old. However due to low sensitivity of tuberculin skin test and resulting too many of false-positive cases, the estimated number of unnecessary chemoprophylaxis was thought to be more than justifiable. Also, as regards the timing for vaccination, it was'thought of as best to give BCG vaccination before one gets infected, which may happen even before 4 years of age. For reasons above, new national BCG policy include direct BCG vaccination for infants younger than 6 months of age. 4. Promotion of a Japanese version of DOTS DOTS (Directly Observed Treatment, Short-course) is, needless to say, a tuberculosis control policy advocated worldwide by World Health Organization (WHO) since early 1990s. Japan has a long history of supporting tuberculosis patients through various activities by health care workers such as home-visit follow-up, although it is worthwhile to note that in a newly amended law there is a reference to having patients take medicine in the law itself as direction by a doctor or a director of the public health care center. 5. Review on Tuberculosis Advisory Committee The Tuberculosis Advisory Committee is a regional commi- ttee that gives advice on issues such as treatment of tuberculosis and hospitalization order based on the law. The amendment includes review on committee members to select at least one committee member from non-medical staff from the perspective of human rights protection. We acknowledge this time's amendment of the law is a significant step forward in the history of national tuberculosis control and it is our sincere hope that this will eventually lead to great improvement of national tuberculosis condition.

Antitubercular Agents↗
PubMed2004

Tuberculosis situation among tribal population of Car Nicobar, India, 15 years after intensive tuberculosis control project and implementation of a national tuberculosis programme.

OBJECTIVE: To assess the tuberculosis (TB) situation in the tribal community of Car Nicobar island 15 years after the national TB programme was implemented in this area after an intensive phase of TB control in 1986. METHODS: The entire population of Car Nicobar was enumerated through a house-to-house survey. Children aged <14 years were tuberculin tested and read for reaction sizes. Individuals aged >15 years were asked about the presence of chest symptoms (cough, chest pain, and unexplained fever for two weeks or longer and haemoptysis), and sputum samples were collected from patients with chest symptoms. Sputum samples were examined for presence of acid-fast bacilli. FINDINGS: Among the 4,543 children enumerated, 4,351 (95.8%) were tuberculin tested and read. Of the 981 children without bacille Calmette-Guerin scars, 161 (16.4%) were infected with TB. A total of 77 cases who were smear-positive for TB were detected from among 10,570 people aged >15 years; the observed smear-positive case prevalence was 728.5 per 100,000. The standardized prevalence of TB infection, annual risk of TB infection, and prevalence of cases smear-positive for TB were 17.0%, 2.5%, and 735.3 per 100,000, respectively. CONCLUSION: The prevalence of TB infection and smear-positive cases of TB increased significantly between 1986 and 2002. Such escalation took place despite the implementation of the national TB programme on this island, which was preceded by a set of special anti-TB measures that resulted in sputum conversion in a substantially large proportion of the smear-positive cases prevalent in the community. The most likely reason for the increase seems to be the absence of a district TB programme with enough efficiency to sustain the gains made from the one-time initial phase of special anti-TB measures. High risk of transmission of TB infection currently observed on this island calls for a drastic and sustained improvement in TB control measures.

Adolescent↗
PubMed1986

A controlled clinical trial of 3- and 5-month regimens in the treatment of sputum-positive pulmonary tuberculosis in South India. Tuberculosis Research Centre, Madras, and National Tuberculosis Institute, Bangalore.

A controlled comparison of 3 short-course regimens was undertaken in patients with newly diagnosed, sputum-positive, pulmonary tuberculosis in South India. The regimens were: R3: rifampin plus streptomycin plus isoniazid plus pyrazinamide daily for 3 months; 5: the same as regimen R3 followed by streptomycin plus isoniazid plus pyrazinamide twice weekly for 2 months; Z5: the same as regimen R5 but without rifampin. The distributions of various pretreatment characteristics were similar in the 3 series. At the end of treatment, 6 patients (3 R3, 3 Z5) of 694 (228 R3, 230 R5, 236 Z5) with drug-sensitive organisms initially were classified as having an unfavorable response. By 24 months (21 months of follow-up for the R3 regimen and 19 months for the R5 and Z5 regimens), a bacteriologic relapse requiring treatment occurred in 20% of 200 R3, 4% of 187 R5, and 13% of 199 Z5 patients, the difference between the R3 and R5 series being highly significant (p = 0.00001). Considering patients with cultures initially resistant to isoniazid, 4 of 57 in the R3 and R5 series combined had an unfavorable response to treatment compared with 13 of 26 in the Z5 series (p less than 0.0001). Of the 4 patients with an unfavorable response in the R3 and R5 series combined, resistance to rifampin emerged in 2. Complaints of arthralgia were made by 45% of the R3 and R5 patients combined and 70% of the Z5 patients (p less than 0.00001). However, chemotherapy was modified in only 5 and 12%, respectively. Jaundice occurred in 7% of the R3 and R5 patients and 1% of the Z5 patients (p less than 0.00001).

Adolescent↗
PubMed2005

[The diagnosis of definitive or probable tuberculosis and latent tuberculosis infection in children with suspected tuberculosis].

Pulmonary tuberculosis (Tbc) continues to be an important cause of morbidity in children in our country and in the world. There are diagnostic difficulties in the evaluation of the patients with suspected Tbc. In our study of 118 cases, the signs or symptoms suggestive of pulmonary Tbc have a microbiologically confirmed ratio of 26% within the cases having a positive tuberculin test result or having a contact with an adult that had Tbc. Thirty-one (26%) patients were diagnosed with definite Tbc, 48 (41%) patients with probable Tbc and 28 (24%) patients with latent Tbc infection. The tuberculin test was positive in 22 (71%) patients with definite Tbc and in 29 (60%) patients with probable Tbc. A history of a contact with an adult having Tbc has been observed in 18 (58%) patients in definite Tbc case group, in 23 (48%) patients in probable Tbc case group and in 13 (46%) patients in latent Tbc infection case group. No significant difference has been observed between patients with definite or probable pulmonary Tbc according to the average age, sex, tuberculin test positivity and history of Tbc contact. The most common clinical symptoms that has been observed in both groups were cough, fever and weight loss and the most common radiological finding that has been found in both groups was persistent infiltration. Definite or probable Tbc cases were treated for a period of 6 months with 3 anti-Tbc drugs. There were no patients who had failed to response to the treatment. These results showed that, the diagnostic criteria used for probable pulmonary Tbc are also useful in detecting the patients who should be treated with anti-Tbc drugs.

Adolescent↗
PubMed1989

[Situation of tuberculosis in the world and the role expected of Japan in the global fight against tuberculosis].

The whole world is divided into 3 groups by the magnitude of tuberculosis problem: namely, developed countries in which tuberculosis is already a minor health problem and continues to decline; NIES and some oil-producing countries in which tuberculosis started to decline significantly; and most developing countries in which tuberculosis is still highly prevalent and no or only a slow decline. Number of new smear positive pulmonary tuberculosis in the whole world in a year is estimated at about 4.5 million, and adding smear negative pulmonary tuberculosis and extra-pulmonary tuberculosis, total number of new tuberculosis patients amounts to 9 to 10 million, and nearly 3 million persons die every year from tuberculosis, and 97% of these cases occur in developing countries. Failure of tuberculosis control in most developing countries could be explained by slow economic development of financial crisis, which caused poor allocation of budget for health including tuberculosis programme and slow development of primary health care. Activities of tuberculosis supervisory teams are weak. Tuberculosis programmes succeeded in developed countries could not be implemented easily in developing countries. New obstacles to the rapid decline of tuberculosis are the epidemic of AIDS, movement of population and lowering concern on tuberculosis problems, and tuberculosis will remain as one of serious global health problems at least for coming several decades. Maintenance of research and training facilities for tuberculosis is needed, however, they have been disappearing in developed countries. Facilities in developing countries might have difficulties to maintain unless financial and technical support is given from developed countries. Japan is the second biggest economic power in the world, and it is our duty to increase ODA for developing countries. In the field of health, Dr. Nakajima started to work as the director-general of WHO since 1988. We have to intensify our technical cooperation in health. As we succeeded to control tuberculosis in the past 40 years and still maintain research and training facilities for tuberculosis, they should be used for the sake of developing countries. Multi-and bi-lateral cooperation in tuberculosis control should also be intensified. The author would like to urge members of the Japanese Society for Tuberculosis to talk about the importance of tuberculosis problem and role expected to Japan in the global fight against tuberculosis to people outside the society so as to have appropriate understanding on global tuberculosis problems.

Developing Countries↗
PubMed2000

Drugs for preventing tuberculosis in HIV infected persons.

BACKGROUND: People with HIV have a increased risk of developing tuberculosis. Preventive therapy may help prevent progression of tuberculosis infection to disease. OBJECTIVES: The objective of this review was to assess the effects of preventive therapy with anti-tuberculosis drugs in people with HIV infection. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Researchers in the field were contacted. SELECTION CRITERIA: Randomised trials of anti-tuberculosis drugs in people with HIV infection but without evidence of active tuberculosis. DATA COLLECTION AND ANALYSIS: One reviewer assessed eligibility and trial quality. Study authors were contacted for additional information. MAIN RESULTS: Six trials were included. Compared to placebo, preventive therapy was associated with a lower incidence of active tuberculosis (relative risk 0.54, 95% confidence interval 0.39 to 0.76). Risk of death (relative risk 0.96, 95% confidence interval 0.82 to 1.13) was not significantly different in the two groups. Incidence of tuberculosis was reduced in people with a positive tuberculin skin test (relative risk 0.24, 95% confidence interval 0.14 to 0.40), but was not significantly lower in those with a negative skin test (relative risk 0.87, 95% confidence interval 0.56 to 1.36). Similarly death was less frequent in those with a positive skin test who received preventive therapy (relative risk 0.77, 95% confidence interval 0.58 to 1.03), but this difference was not observed among those with a negative skin test (relative risk 1.07, 95% confidence interval 0.88 to 1.30). Each regimen (isoniazid alone, isoniazid plus rifampicin, isoniazid plus rifampicin plus pyrazinamide, rifampicin plus pyrazinamide) had similar protective effects against active tuberculosis for people with positive skin tests. REVIEWER'S CONCLUSIONS: Preventive therapy appears to be effective in reducing incidence of tuberculosis, and death from tuberculosis in HIV infected adults with a positive tuberculin skin test, at least in the short to medium term.

AIDS-Related Opportunistic Infections↗
PubMed1999

Genomic analysis reveals variation between Mycobacterium tuberculosis H37Rv and the attenuated M. tuberculosis H37Ra strain.

Mycobacterium tuberculosis H37Ra is an attenuated tubercle bacillus closely related to the virulent type strain M. tuberculosis H37Rv. Despite extensive study, the reason for the decreased virulence of M. tuberculosis H37Ra has not been determined. A genomic approach was therefore initiated to identify genetic differences between M. tuberculosis H37Rv and M. tuberculosis H37Ra as a means of pinpointing the attenuating mutation(s). Digestion with the rare-cutting restriction endonuclease DraI revealed two polymorphisms between the strains: a 480-kb fragment in M. tuberculosis H37Rv was replaced by two fragments of 220 and 260 kb in M. tuberculosis H37Ra, while there was a approximately 7.9-kb DraI fragment in M. tuberculosis H37Ra that had no counterpart in M. tuberculosis H37Rv. As the M. tuberculosis insertion sequence IS6110 contains a single DraI restriction site, it was considered possible that these polymorphisms were the result of IS6110 transposition events in M. tuberculosis H37Ra, events that may have inactivated virulence genes. The 7.9-kb polymorphism was found to be due to the presence of the previously described H37Rv RvD2 deletion in M. tuberculosis H37Ra, with sequence analysis suggesting an IS6110-mediated deletion mechanism for loss of RvD2. Three other IS6110-catalyzed deletions from the M. tuberculosis H37Rv chromosome (RvD3 to RvD5) were also identified, suggesting that this mechanism plays an important role in genome plasticity in the tubercle bacilli. Comparative mapping and sequencing revealed that the 480-kb polymorphism was due to an IS6110 insertion in M. tuberculosis H37Ra near oriC. Complementation of M. tuberculosis H37Ra with a 2.9-kb restriction fragment from M. tuberculosis H37Rv that encompassed the IS6110 insertion did not increase the survival of recombinant M. tuberculosis H37Ra in mice. In conclusion, this study describes the presence and mechanisms of genomic variation between M. tuberculosis H37Ra and M. tuberculosis H37Rv, although the role that they play in the attenuation of M. tuberculosis H37Ra is unclear.

Animals↗
PubMed1997

[Clinical course of HIV-infected tuberculosis patients who admitted to the tuberculosis isolation ward: current problems of medical care].

To clarify the problems of medical care of HIV-infected tuberculosis patients, we investigated clinical course of six cases admitted to our tuberculosis isolation ward. All cases were sputum smear positive for tubercle bacilli at the time of diagnosis of tuberculosis. HIV-positive was confirmed at the same time or soon after the diagnosis of tuberculosis in four cases. CD4+ cell count was on the average 21/mm3 on admission, and all cases were defined as acquired immunodeficiency syndrome (AIDS) by the criteria of AIDS surveillance committee in Japan. Two patients presented with miliary tuberculosis and five documented evidence for intrathoracic and/or cervical lymph node involvement. All cases but one responded well to antituberculosis drugs, and sputum smears and cultures became negative soon after the initiation of therapy. However, the patients were still needed to be hospitalized for the treatment and control of complications other than tuberculosis after sputum negative conversion, and they stayed in the isolation rooms of our tuberculosis ward for 110 +/- 49 days. During the treatment for tuberculosis, each patient developed 3 to 8 complications of HIV infection such as pneumocystis carinii pneumonia (PCP) (four cases), bacterial infection (four cases), neuropathy (four cases), and HIV encephalopathy (three cases). The last two complication worsened active daily life. White blood cell count was more likely to fall when sulfamethoxazole/trimethoprim mixture for the prevention of PCP and antituberculosis drugs were administered together. In three cases, ST mixture could not be continued, then two patients developed PCP after changing to an alternative pentamidine inhalation. Although three patients discharged from our tuberculosis ward, four died of AIDS related complications other than tuberculosis, one died of tuberculosis (multidrug-resistant M. tuberculosis strain was not documented initially but was detected five months later), one died of tuberculosis meningitis after the discharge, and one was lost because he returned to his own country. The survival time between the start of treatment and death ranged from 90 to 244 days in five cases. Integrated medical care system both for HIV and tuberculosis is warranted for the management of HIV-infected tuberculosis patients since they suffer many complication in addition to tuberculosis. A guideline of methods and duration of isolation for tuberculosis is needed for the most effective care of HIV-infected tuberculosis patients in Japan.

AIDS-Related Opportunistic Infections↗
PubMed2006

Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa.

BACKGROUND: The epidemics of HIV-1 and tuberculosis in South Africa are closely related. High mortality rates in co-infected patients have improved with antiretroviral therapy, but drug-resistant tuberculosis has emerged as a major cause of death. We assessed the prevalence and consequences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in a rural area in KwaZulu Natal, South Africa. METHODS: We undertook enhanced surveillance for drug-resistant tuberculosis with sputum culture and drug susceptibility testing in patients with known or suspected tuberculosis. Genotyping was done for isolates resistant to first-line and second-line drugs. RESULTS: From January, 2005, to March, 2006, sputum was obtained from 1539 patients. We detected MDR tuberculosis in 221 patients, of whom 53 had XDR tuberculosis. Prevalence among 475 patients with culture-confirmed tuberculosis was 39% (185 patients) for MDR and 6% (30) for XDR tuberculosis. Only 55% (26 of 47) of patients with XDR tuberculosis had never been previously treated for tuberculosis; 67% (28 of 42) had a recent hospital admission. All 44 patients with XDR tuberculosis who were tested for HIV were co-infected. 52 of 53 patients with XDR tuberculosis died, with median survival of 16 days from time of diagnosis (IQR 6-37) among the 42 patients with confirmed dates of death. Genotyping of isolates showed that 39 of 46 (85%, 95% CI 74-95) patients with XDR tuberculosis had similar strains. CONCLUSIONS: MDR tuberculosis is more prevalent than previously realised in this setting. XDR tuberculosis has been transmitted to HIV co-infected patients and is associated with high mortality. These observations warrant urgent intervention and threaten the success of treatment programmes for tuberculosis and HIV.

Adult↗