SEARCH · PubMed Health

Results for “Tuberculosis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed1993

Large-scale DNA fingerprinting of Mycobacterium tuberculosis strains as a tool for epidemiological studies of tuberculosis.

We conducted a large-scale DNA fingerprinting analysis of Mycobacterium tuberculosis strains in a country in which tuberculosis is endemic (Tunisia) in order to evaluate the importance of microepidemics in the maintenance of the disease within the population. The genetic polymorphisms of 201 strains of M. tuberculosis isolated from 196 unrelated patients living in four districts of northern Tunisia during a 3-year period were studied by restriction fragment length polymorphism (RFLP) analysis by using the insertion sequence IS6110 as a probe. Seventy-three strains isolated from 68 patients living in the districts of Tunis, Nabeul, and Jendouba generated 67 different RFLPs, indicating a high degree of polymorphism of the M. tuberculosis strains within these areas. In contrast, the 128 strains isolated from individuals in the district of Menzel Bourguiba appeared much less heterogeneous since they often generated identical or very similar fingerprints. Seventeen of 29 cases (58%) of active tuberculosis in the city of Menzel Bourguiba could be traced to as few as four M. tuberculosis strains. These results indicate the persistence of underestimated microepidemics in this region. The RFLP typing of a large number of randomly collected strains provides a general picture of the strains involved in tuberculosis. The systematic study of limited areas where tuberculosis is endemic can provide evidence for the existence of persisting epidemics. This stresses the different problems which remain to be solved in order to improve the control of tuberculosis.

DNA Fingerprinting↗

PubMed1998

Comparison of Roche Cobas Amplicor Mycobacterium tuberculosis assay with in-house PCR and culture for detection of M. tuberculosis.

The new Roche Cobas Amplicor Mycobacterium tuberculosis assay, which is a semiautomated version of the manually performed Roche Amplicor M. tuberculosis test, was compared to culture and an IS6110-based in-house PCR protocol. A total of 1,681 specimens from 833 patients, including specimen types other than sputum, were tested in parallel by both the in-house PCR and the Cobas Amplicor M. tuberculosis assay. After we resolved discrepant PCR results, the sensitivity, specificity, and positive and negative predictive values for the Cobas Amplicor M. tuberculosis assay were 66.33, 99.71, 94.36, and 97.66%, respectively. The corresponding values for the in-house PCR were 91.08, 99.85, 97.87, and 99.37%, respectively. For culture- and smear-positive specimens, the sensitivity of the Cobas Amplicor M. tuberculosis test was 96.42% (in-house PCR, 100%). If only smear-negative sputum specimens were considered, the Cobas Amplicor M. tuberculosis assay exhibited a sensitivity of 45.45% (in-house PCR, 63.63%) relative to that of culture. With a modified protocol for DNA extraction (washing of samples plus ultrasonication), both PCR methods performed better with gastric aspirates than with sputum samples (sensitivity of the Cobas Amplicor M. tuberculosis assay with smear-negative gastric aspirates, 70.00%; sensitivity of in-house PCR, 90.00%). With dithiothreitol being used for liquefaction of specimens in this study, the Cobas Amplicor M. tuberculosis assay exhibited an inhibition rate of 9.16%. In our view, the new Cobas Amplicor M. tuberculosis test (i) is well suited for typing of smear-positive specimens, (ii) may also be applied to gastric aspirates and other types of specimens if DNA extraction methods are modified appropriately, and (iii) exhibits a sensitivity with smear-negative sputum specimens which makes it recommendable that a minimum of three samples from the same patient be tested.

Bronchoalveolar Lavage Fluid↗

PubMed2003

Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis.

OBJECTIVE: This study sought to determine the impact of the World Health Organization's directly observed treatment strategy (DOTS) compared with that of DOTS-plus on tuberculosis deaths, mainly in the developing world. DESIGN: Decision analysis with Monte Carlo simulation of a Markov decision tree. DATA SOURCES: People with smear positive pulmonary tuberculosis. DATA ANALYSIS: Analyses modelled different levels of programme effectiveness of DOTS and DOTS-plus, and high (10%) and intermediate (3%) proportions of primary multidrug resistant tuberculosis, while accounting for exogenous reinfection. MAIN OUTCOME MEASURE: The cumulative number of tuberculosis deaths per 100 000 population over 10 years. RESULTS: The model predicted that under DOTS, 276 people would die from tuberculosis (24 multidrug resistant and 252 not multidrug resistant) over 10 years under optimal implementation in an area with 3% primary multidrug resistant tuberculosis. Optimal implementation of DOTS-plus would result in four (1.5%) fewer deaths. If implementation of DOTS-plus were to result in a decrease of just 5% in the effectiveness of DOTS, 16% more people would die with tuberculosis than under DOTS alone. In an area with 10% primary multidrug resistant tuberculosis, 10% fewer deaths would occur under optimal DOTS-plus than under optimal DOTS, but 16% more deaths would occur if implementation of DOTS-plus were to result in a 5% decrease in the effectiveness of DOTS CONCLUSIONS: Under optimal implementation, fewer tuberculosis deaths would occur under DOTS-plus than under DOTS. If, however, implementation of DOTS-plus were associated with even minimal decreases in the effectiveness of treatment, substantially more patients would die than under DOTS.

Cost-Benefit Analysis↗

PubMed1999

[Factors for the onset of and the exacerbation of tuberculosis. 5. The infection and prognosis of tuberculosis among patients with immunodeficiency, especially HIV-infected patients].

The number of people infected with human immunodeficiency virus (HIV) is gradually increasing in Japan, and the morbidity rate from tuberculosis in the Japanese people is high. Accordingly, the number of cases with both infections is considered to increase in the future. Our hospital has already encountered 22 cases of HIV associated tuberculosis. HIV infects mainly CD4-positive cells. The extreme decrease in the cell count results in serious cellular immunological disorder. CD4-positive cell disorder induces disorders of B lymphocytes, cytotoxic T cells, natural killer cells, and macrophage functions. These destructive conditions show the state of immunodeficiency including macrophage that are most important for defense of acid-fast bacterial infection. Migration and activation of macrophages with cytokines derived from T cells are impaired to induce the following phenomena: hypoplasia of granuloma, failure of tubercle bacillus sppression, the spread to regional lymph nodes (hilar or mediastinal lymph nodes), and hematogenous dissemination. On this occasion, caseous necrosis and cavitation are unlikely to occur, and false-negative tuberculin reaction is often observed. The incidence of severe cases, which include miliary tuberculosis, tuberculous meningitis, etc., and extrapulmonary tuberculosis, are high among acquired immunodeficiency syndrome (AIDS)-associated tuberculosis cases. HIV-infected tuberculosis cases are generally regarded as endogenous exacerbation, but they include primary infection and reinfection as well. Even during the treatment for drug-sensitive strains particularly, some cases may have reinfection with multidrug-resistant bacteria, suggesting that caution should be taken against this point. Conversely, the association of tuberculosis is a factor for the poor prognosis of HIV infection, since it facilitates the development of HIV infection. If the bacteria belong to a drug-sensitive strain, the infection with them responds well to antituberculous drugs, the same as in tuberculosis cases without HIV infection, showing a favorable prognosis. However, the mortality rate of infection with multidrug-resistant tuberculosis is extremely high.

Disease Progression↗

PubMed2001

Serological response (Western blot) to fractions of Mycobacterium tuberculosis sonicate antigen in tuberculosis patients and contacts.

OBJECTIVE: To assess the serological response to fractions of Mycobacterium tuberculosis sonicate antigen by Western blot analysis in patients with tuberculosis and contacts. METHODS: We studied 71 individuals including 43 patients with active tuberculosis, 16 contacts and 12 healthy blood donors. For Western blot analysis, M. tuberculosis (H37Rv strain) sonicate antigen extract was fractionated by electrophoresis on polyacrylamide gel (SDS-PAGE). RESULTS: We obtained antibody responses directed against four antigenic fractions with molecular weights of 71, 65, 26-38 and 19 kDa. Sixty per cent of pleural tuberculosis and 52.4% of smear-positive pulmonary tuberculosis had whole responses against all four fractions; there were no partial responses in these groups. For patients with smear-negative pulmonary tuberculosis whole responses were 17.6% and partial responses 41.2%. All contacts whose tuberculin tests converted from negative to positive (three cases) reacted exclusively against the 19 kDa fraction. CONCLUSIONS: Western blot-positive results in patients with pleural and smear-positive pulmonary tuberculosis were characterised by a whole pattern against all four antigenic fractions, whereas patients with smear-negative pulmonary tuberculosis showed heterogeneous results. The exclusive response against the 19 kDa fraction observed in contacts with tuberculin conversion could help to identify candidates for preventive therapy.

Adult↗

PubMed2003

[Significance of tuberculosis of the large bronchi in the diagnosis and treatment of restrictive forms of pulmonary tuberculosis].

A total of 1223 new cases of restrictive forms of pulmonary tuberculosis were examined. Of them 652 and 598 patients were followed up in the period of the good (1980-1984) and poor (1997-2001) tuberculosis epidemiological situation, respectively. A comparative analysis has indicated that there has been recently a rise in the incidence of tuberculosis of main bronchi from 10.5 to 18.0%, which most commonly complicates intrathoracic lymph nodal or infiltrative pulmonary tuberculosis. A more severe clinical course and a more frequent bacterial isolation have been ascertained mainly in infiltrative, ulcerative, and fistular forms of bronchial tuberculosis irrespective of the form of pulmonary tuberculosis. The comprehensive examination of patients with restrictive pulmonary tuberculosis is certain to include bronchial fibroscopy that may determine the form and phase of bronchial tuberculosis, the rate of a process in the lung, make and differentiate its diagnosis, use systematic and topical therapy (with hydrocortisone aerosols, GINK, streptomycin), and cure bronchial tuberculosis within 2-3 months.

Adult↗

PubMed1998

[Multidrug-resistant tuberculosis. 2. Mechanisms of drug-resistance in Mycobacterium tuberculosis--genetic mechanisms of drug-resistance].

Multidrug-resistant Mycobacterium tuberculosis infection is now world wide health problem. However, according to the recent advances of molecular biological technics, some of the genetic mechanisms of drug-resistance of M. tuberculosis has been uncovered. Generally, drug-resistance of M. tuberculosis was caused by point mutations in chromosomal gene. In isoniazid (INH) resistant M. tuberculosis, mutations and genetic deletions in catalase-peroxidase gene (katG), inhA gene, or alkyl hydroperoxide reductase gene were reported. We also found that about 15% of INH-resistant M. tuberculosis isolates lacked katG gene, and these isolates showed highly resistance to INH with MIC > or = 64 micrograms/ml. On the other hand, mutations and other genetic alterations in RNA polymerase beta subunit gene (rpoB) were the major mechanisms of resistance to rifampicin (RFP) with high frequencies of 90% or more. Our evaluation of the relationship between RFP susceptibility and genetic alteration in rpoB gene also showed that 95% of RFP-resistant M. tuberculosis isolates involved genetic alterations in 69 bp core region of rpoB gene. Moreover, these genetic alterations in rpoB gene were suspected as the resistant mechanism to other rifamycin antituberculosis drugs, such as rifabutin and KRM-1648. In addition, it was reported that point mutations in 16S rRNA gene (rrs) and ribosomal protein S12 gene (rpsL) induced M. tuberculosis as streptomycin (SM) resistant phenotype. We analyzed genetic alternations in rpsL gene of clinically isolates of M. tuberculosis, about 60% of SM resistant isolates were shown point mutation in this gene ant they were all high SM-resistant with MIC > or = 256 micrograms/ml. Furthermore, nicotinamidase (pncA) gene, DNA gyrase A subunit (gyrA) gene, and embB gene were reported as the responsible gene to pyrazinamide-, quinolone- and ethambutol-resistance, respectively. Although all mechanisms of drug-resistance were still unclear, these informations are very useful and helpful for development of rapid diagnosis system of drug-resistant M. tuberculosis.

Drug Resistance, Microbial↗

PubMed1994

Tuberculosis and AIDS: a retrospective, longitudinal, multicentre study of Italian AIDS patients. Italian group for the study of tuberculosis and AIDS (GISTA)

We report the results of a retrospective, longitudinal, multicentre study which estimated the cumulative incidence of tuberculosis in patients who eventually develop AIDS, investigated the characteristics of AIDS patients in relation to the development of tuberculosis, and endeavoured to determine the degree of HIV-induced immunosuppression at which tuberculosis occurs. The Infectious Disease Units of 23 hospitals located in 11 of the 20 regions of Italy participated in this study. We investigated 1691 patients with AIDS diagnosed in 1988 and 1989 and reported to the National AIDS Registry by participating units before the end of December 1990. By that time M. tuberculosis had been cultured from 193 patients (11.4%). Compared with intravenous drug users (the largest HIV transmission category), only homosexual men had a statistically significant lower risk of tuberculosis (relative risk = 0.65; 95% confidence interval 0.43-0.99). The median count of CD4+ lymphocytes at the time tuberculosis was diagnosed was 82/mm3 (range 1-752); only four patients (2.1%) had CD4+ lymphocyte counts of more than 500/mm3, and 36 (18.7%) of over 200/mm3. We conclude that in Italy the proportion of AIDS patients who develop tuberculosis is higher than in other industrialised countries and differences in the incidence of tuberculosis among various HIV-transmission categories are less marked than in other western countries. Tuberculosis associated with HIV infection may occur in those with widely differing CD4+ counts, although the risk increases consistently in proportion to the degree of immunosuppression.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Enhancing the protective efficacy of Mycobacterium bovis BCG vaccination against tuberculosis by boosting with the Mycobacterium tuberculosis major secretory protein.

Tuberculosis continues to ravage humanity, killing 2 million people yearly. Most cases occur in areas of the world to which the disease is endemic, where almost everyone is vaccinated early in life with Mycobacterium bovis BCG, the currently available vaccine against tuberculosis. Thus, while more-potent vaccines are needed to replace BCG, new vaccines are also needed to boost the immune protection of the 4 billion people already vaccinated with BCG. Until now, no booster vaccine has been shown capable of significantly enhancing the level of protective immunity induced by BCG in the stringent guinea pig model of pulmonary tuberculosis, the "gold standard" for testing tuberculosis vaccines. In this paper, we describe a booster vaccine for BCG comprising the purified recombinant Mycobacterium tuberculosis 30-kDa protein, the major secreted protein of this pathogen. In the guinea pig model of pulmonary tuberculosis, boosting BCG-immunized animals once with the 30-kDa protein greatly increased cell-mediated and humoral immune responses to the protein in three consecutive experiments. Most importantly, boosting BCG-immunized animals once with the 30-kDa protein significantly enhanced protective immunity against aerosol challenge with highly virulent M. tuberculosis, as evidenced by a significantly reduced lung and spleen burden of M. tuberculosis compared with those for nonboosted BCG-immunized animals (mean additional reduction in CFU of 0.4 +/- 0.1 log in the lung [P = 0.03] and 0.6 +/- 0.1 log in the spleen [P = 0.002]). This study suggests that administering BCG-immunized people a booster vaccine comprising the 30-kDa protein may enhance their level of immunoprotection against tuberculosis.

Animals↗

PubMed2000

Evaluating the usefulness of the ICT tuberculosis test kit for the diagnosis of tuberculosis.

BACKGROUND: Early diagnosis of tuberculosis is crucial, especially in Korea, where tuberculosis is endemic. AIMS: To evaluate the validity of the ICT tuberculosis test (ICT) in early diagnosis of tuberculosis. METHODS: Sixty eight patients with tuberculosis were tested; 37 had no history of previous tuberculosis (patient group 1), and 31 had reactivated tuberculosis (patient group 2). The control groups comprised 77 subjects: 25 healthy adults, 35 hospital workers, and 17 inpatients with non-tuberculous respiratory diseases. RESULTS: The diagnostic sensitivities of ICT were 73% in patient group 1 and 87.1% in patient group 2. In two patients with extrapulmonary tuberculosis, both tested positive using ICT. The specificities of ICT were 88%, 94%, and 94% in healthy adults, hospital workers, and non-tuberculous patients, respectively. CONCLUSIONS: ICT is a useful tool for the diagnosis of tuberculosis.

Adult↗

PubMed2001

Tuberculosis control in the era of the HIV epidemic: risk of tuberculosis infection in Tanzania, 1983-1998.

SETTING: In Tanzania, a national tuberculosis programme (NTP) was established in 1979 based on the principles currently known as the World Health Organization DOTS strategy. From the period 1983-1987 to 1994-1998, notification rates of smear-positive tuberculosis increased from 32 to 69 per 100,000 population, mainly due to the human immunodeficiency virus (HIV) epidemic. OBJECTIVES: To estimate the trend in the annual risk of tuberculosis infection and to establish to what extent the opposing forces of improved tuberculosis control and HIV have had an impact on tuberculosis transmission. METHODS: Three national surveys were conducted in Tanzania among primary school children at 5-year intervals. The annual risk of tuberculosis infection and its trend were determined by tuberculin skin testing. RESULTS: The annual risk of infection in children without BCG scar using the criterion '17 mm + 2 x 18 mm' or more was estimated at 1.1% in 1983-1987, 1.0 in 1988-1992, and 0.9% in 1993-1998. There appears to have been little change in the annual risk of infection over the study period, either when using other criteria to define infection or in children with a BCG scar. The estimated number of infections per notified case decreased over time from 36 to 19. CONCLUSIONS: Despite strongly increased tuberculosis notification rates in adults, associated with the HIV epidemic, the risk of tuberculosis infection in children appears to have been stable over the past 15 years in Tanzania. This remarkable achievement is probably due to the impact of the NTP on tuberculosis transmission.

Adolescent↗

PubMed1962

The trend of tuberculosis in Japan during the period 1953-58. Comparison of the results of tuberculosis prevalence surveys.

In 1953 a survey of tuberculosis prevalence, carried out by the Japanese Ministry of Health and Welfare on a statistical sampling basis, yielded valuable data on the status of tuberculosis in Japan. In 1954, a follow-up investigation, conducted on one-third of the areas surveyed in 1953, gave information which helped to elucidate the trend of tuberculosis and changes in the tuberculin-positive rate and in the incidence of the disease. Five years after the first survey, the Ministry of Health and Welfare conducted yet another survey, again by the stratified sampling method, to obtain basic information on the present status of tuberculosis, and, by comparing the results with those of the 1953 survey, to assess the trend of tuberculosis during the five years in question.The 1958 survey revealed that the prevalence of active tuberculosis was practically the same as in 1953, a decline in the number of active cases among persons under 35 years of age having been offset by an increase in older age-groups. The inactive form, on the other hand, decreased noticeably. The prevalence of primary tuberculosis was considerably lower, and cavitary tuberculosis likewise showed a tendency to decrease.These facts suggest that the tuberculosis situation in Japan is tending to improve, but at the same time they confirm the need to continue the fight against the disease.

Aggression↗

PubMed1982

[Models of tuberculosis control in countries with low tuberculosis prevalence].

To rationalize tuberculosis control in countries with low tuberculosis prevalence it is necessary to evaluate continuously some control measures and to propose suitable modifications. For years Czechoslovakia is taking part in the international research of methods of tuberculosis control; in compliance with the results of these studies its programme of tuberculosis control is being modified. Decision processes are more difficult, when measures till now applied should be limited or given up. In such cases it is necessary to evaluate not only the efficiency of defined health measures but also their possibilities of application, acceptability and influence on the tuberculosis situation in all. For the choice of appropriate models of tuberculosis control the application of experience from other countries should be regarded. However sometimes it is not possible to use this experience in the own country because there are obvious differences in other conditions. Mathematical simulation models may by of good help in the decision process answering the purpose of discerning the effect of different variants of the control measure on the epidemiological trends. For this purpose reliable statistic data should be available. To get such information a central tuberculosis register was established on CSR gathering data on new cases of tuberculosis, on relapses, on the further development of the cases of tuberculosis registered and on data concerning the quality of case-finding, diagnostics and therapy.

Adult↗

PubMed1996

The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices.

This report updates and replaces previous recommendations regarding the use of Bacillus of Calmette and Guerin (BCG) vaccine for controlling tuberculosis (TB) in the United States (MMWR 1988;37:663-4, 669-75). Since the previous recommendations were published, the number of TB cases have increased among adults and children, and outbreaks of multidrug-resistant TB have occurred in institutions. In addition, new information about the protective efficacy of BCG has become available. For example, two meta-analyses of the published results of BCG vaccine clinical trials and case-control studies confirmed that the protective efficacy of BCG for preventing serious forms of TB in children is high (i.e., > 80%). These analyses, however, did not clarify the protective efficacy of BCG for preventing pulmonary TB in adolescents and adults; this protective efficacy is variable and equivocal. The concern of the public health community about the resurgence and changing nature of TB in the United States prompted a re-evaluation of the role of BCG vaccination in the prevention and control of TB. This updated report is being issued by CDC, the Advisory Committee for the Elimination of Tuberculosis, and the Advisory Committee on Immunization Practices, in consultation with the Hospital Infection Control Practices Advisory Committee, to summarize current considerations and recommendations regarding the use of BCG vaccine in the United States. In the United States, the prevalence of M. tuberculosis infection and active TB disease varies for different segments of the population; however, the risk for M. tuberculosis infection in the overall population is low. The primary strategy for preventing and controlling TB in the United States is to minimize the risk for transmission by the early identification and treatment of patients who have active infectious TB. The second most important strategy is the identification of persons who have latent M. tuberculosis infection and, if indicated, the use of preventive therapy with isoniazid to prevent the latent infection from progressing to active TB disease. Rifampin is used for preventive therapy for persons who are infected with isoniazid-resistant strains of M. tuberculosis. The use of BCG vaccine has been limited because a) its effectiveness in preventing infectious forms of TB is uncertain and b) the reactivity to tuberculin that occurs after vaccination interferes with the management of persons who are possibly infected with M. tuberculosis. In the United States, the use of BCG vaccination as a TB prevention strategy is reserved for selected persons who meet specific criteria. BCG vaccination should be considered for infants and children who reside in settings in which the likelihood of M. tuberculosis transmission and subsequent infection is high, provided no other measures can be implemented (e.g., removing the child from the source of infection). In addition, BCG vaccination may be considered for health-care workers (HCWs) who are employed in settings in which the likelihood of transmission and subsequent infection with M. tuberculosis strains resistant to isoniazid and rifampin is high, provided comprehensive TB infection-control precautions have been implemented in the workplace and have not been successful. BCG vaccination is not recommended for children and adults who are infected with human immunodeficiency virus because of the potential adverse reactions associated with the use of the vaccine in these persons. In the United States, the use of BCG vaccination is rarely indicated. BCG vaccination is not recommended for inclusion in immunization or TB control programs, and it is not recommended for most HCWs. Physicians considering the use of BCG vaccine for their patients are encouraged to consult the TB control programs in their area.

Adult↗

PubMed1997

Estimation of the impact of the human immunodeficiency virus infection on tuberculosis: tuberculosis risks re-visited?

The human immunodeficiency virus (HIV) infection has both a direct and an indirect effect on the incidence of tuberculosis. The direct effect is due to the increased number of cases among HIV-infected individuals because of their enhanced susceptibility to the disease. The indirect effect is increased transmission of Mycobacterium tuberculosis infection in a community with high levels of dual infection, as a consequence of infectious cases occurring in HIV-infected persons. The risk of infection by M. tuberculosis in the population will then increase, as will the number of tuberculosis cases in the general population. According to the World Health Organization, over 4 million people are estimated to be dually infected with HIV and M. tuberculosis world-wide. In 1990, it was estimated that 300,000 new TB cases (4% of total new cases) were attributable to HIV infection; around 1.4 million cases are expected per year by 2000 (equivalent to about 14% of expected cases), thus increasing the reservoir of tuberculosis patients capable of transmitting the infection to others, and increasing the burden on the already overstretched National Tuberculosis Control Programmes, especially in resource-poor countries. This paper is a review of methods suggested to quantify the effect of the interaction between HIV infection and tuberculosis at population level, and more particularly the effect of HIV on the risk of tuberculosis infection.

AIDS-Related Opportunistic Infections↗

PubMed1998

Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Joint Tuberculosis Committee of the British Thoracic Society.

BACKGROUND: The guidelines on chemotherapy and management of tuberculosis in the United Kingdom have been reviewed and updated. METHODS: A subcommittee was appointed by the Joint Tuberculosis Committee (JTC) of the British Thoracic Society to revise the guidelines published in 1990 by the JTC. In preparing the revised guidelines the authors took account of new published evidence and graded the strength of evidence for their recommendations. The guidelines have been approved by the JTC and the Standards of Care Committee of the British Thoracic Society. RECOMMENDATIONS: (1) Patients with tuberculosis should be notified. (2) In view of the rising incidence of drug resistance, bacteriological confirmation and drug susceptibility testing should be sought whenever possible. (3) A six month short course regimen, with four drugs in the initial phase, should be used for all forms of tuberculosis, except meningitis, in both adults and children. (4) The fourth drug (ethambutol) in the initial phase can be omitted in certain circumstances. (5) Treatment of all patients should be supervised by physicians with full training in the management of tuberculosis and with direct working access to tuberculosis nurse specialists or health visitors. (6) Advice is given on (a) management in special situations and patient groups, (b) drug interactions, and special precautions and pretreatment screening, (c) chemoprophylaxis for different groups, and (d) the management of single and multiple drug resistance. (7) Advice is given on follow up after treatment and the organisational framework for tuberculosis services. (8) The role of directly observed therapy is discussed. (9) The management of multidrug resistant tuberculosis is explained in outline: such patients should be managed by physicians with special experience and in close liaison with the Mycobacterium Reference Units, and in hospitals with appropriate isolation facilities. (10) Infection control and segregation for such patients and for patients with dual infection with human immunodeficiency virus (HIV) and tuberculosis are covered in an appendix.

Adult↗

PubMed2006

Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design.

Tuberculosis remains a substantial global health problem despite effective drug treatments. The efficacy of BCG, the only available vaccine, is variable, especially in tuberculosis-endemic regions. Recent advances in the development of new vaccines against tuberculosis mean that the first of these are now entering into early clinical trials. A recombinant modified vaccinia virus Ankara expressing a major secreted antigen from Mycobacterium tuberculosis, antigen 85A, was the first new tuberculosis vaccine to enter into clinical trials in September 2002. This vaccine is known as MVA85A. In a series of phase I clinical trials in the UK, MVA85A had an excellent safety profile and was highly immunogenic. MVA85A was subsequently evaluated in a series of phase I trials in The Gambia, a tuberculosis-endemic area in west Africa. This vaccine is the only new subunit tuberculosis vaccine to enter into clinical trials in Africa to date. Here, we discuss some of the issues that were considered in the protocol design of these studies including recruitment, inclusion and exclusion criteria, reimbursement of study participants, and HIV testing. These issues are highly relevant to early clinical trials with all new tuberculosis vaccines in the developing world.

Acyltransferases↗

PubMed2002

Bacillarity at autopsy in pulmonary tuberculosis. Mycobacterium tuberculosis is often disseminated.

The aim of this investigation was to quantify dissemination of Mycobacterium tuberculosis infection in patients with pulmonary tuberculosis and to show the pattern of eradication during treatment. The study is based on 98 out of the 113 patients with pulmonary tuberculosis who died during their admission to hospital in the Municipality of Copenhagen from 1963 to 1971. These patients had cultures for M. tuberculosis performed from different organs at autopsy: 78% treated <=100 days had dissemination of bacteria, cultured with decreasing frequency in the lungs, spleen, liver, and kidneys, respectively. In comparison, 23% treated >100 days had dissemination of bacteria, among which 50% occurred in patients with records of poor treatment compliance, 14% in patients with good treatment compliance. 81% of all patients had at least one chest x-ray judged to be without a miliary pattern. This study emphasizes that M. tuberculosis is often disseminated to organs other than the lungs in severe pulmonary tuberculosis. Eradication of bacteria in these organs can take several months. This observation adds to our understanding of the natural history of tuberculosis: M. tuberculosis is a resilient organism that can adapt to a wide variety of environmental conditions.

Adult↗