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In a number of developing countries, particularly in Sub-Saharan Africa, infection with both M. tuberculosis and human immunodeficiency virus (HIV) is highly prevalent. HIV infection results in an impairment of the immune system and entails a substantial risk of TB in those individuals who are or become infected with the tubercle bacillus. Because persons with both infections have an increased risk of developing clinical TB and further transmitting M. tuberculosis infection, some of these countries are facing, or will have to face, a rapid upsurge of the TB problem. The interaction between HIV and M. tuberculosis infection poses a serious health problem which will result in a major increase in disease, death and health care service needs in many countries. Immediate action at the global, national and local levels is needed to address this problem. In their national plans of action, national AIDS and TB control programmes should include coordinated activities to reduce the impact of the problem and international organizations and donor countries should be encouraged to support them technically and financially. Control of this TB epidemic linked with HIV infection will depend largely on the availability of prompt diagnosis and adequate treatment for TB, and possibly of effective chemoprophylaxis, not just for HIV-infected persons but for other groups as well. To deal with this problem, a number of issues need to be studied urgently. In addition, a number of immediate steps can be taken by control programmes.
BACKGROUND: Mycobacterium vaccae has been advocated for immunotherapy in the treatment of tuberculosis and other infections caused by mycobacteria. OBJECTIVES: The objective of this review was to assess the effects of Mycobacterium vaccae for treating tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials register, Medline, Embase and reference lists of articles. We also contacted organisations and individuals working in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of preparations of whole, killed Mycobacterium vaccae in patients with tuberculosis. DATA COLLECTION AND ANALYSIS: One reviewer assessed trial quality and extracted data. MAIN RESULTS: Four trials met the inclusion criteria. There was no effect on mortality (2 trials, RR 1.01, 95% CI 0.50 to 2.04); no consistent effect on sputum negativity or sputum culture; and a high level of adverse reactions. REVIEWER'S CONCLUSIONS: Immunotherapy with Mycobacterium vaccae does not appear to benefit patients with tuberculosis.
BACKGROUND: The number of people infected with tuberculosis continues to rise world-wide. Rifampicin-containing treatment regimens can achieve high cure rates. Intermittent drug treatment delivered in the community has the potential to improve adherence to treatment. OBJECTIVES: The objective of this review was to compare the effectiveness of rifampicin-containing short-course chemotherapy regimens, given two or three times a week, with similar regimens given daily in patients with pulmonary tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of any multi-drug regimen containing rifampicin in patients with confirmed pulmonary tuberculosis. Treatment had to be given up to three times a week for up to nine months, with any initial daily dosing period not more than one month, and was compared to daily dosing throughout for the same period. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. MAIN RESULTS: One trial involving 399 patients was included. The trial compared treatment three times per week with daily treatment for six months. There was no difference in cure rate (198 out of 199 people in the intermittent group compared to all 200 in the daily group), but 5 patients relapsed in the group receiving intermittent therapy compared to one in the group receiving the daily regimen. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the equivalence of effect between fully intermittent, rifampicin-containing short-course chemotherapy and similar daily therapy in patients with pulmonary tuberculosis. Larger randomised studies are required to establish the effectiveness of fully intermittent, short-course chemotherapy.
Information on the risk of tuberculous infection in the Netherlands has been linked with information on the incidence of tuberculosis, in an attempt to estimate the risks of developing the disease following infection or reinfection. It was postulated that: (a) those with a recent primary infection had a characteristic risk of developing progressive primary tuberculosis; (b) those with a distant (i.e. not recent) primary infection and a recent reinfection had a characteristic risk of developing exogenous tuberculosis; and (c) those with a distant primary infection but no recent reinfection had a characteristic risk of developing endogenous tuberculosis. The information on the risk of tuberculous infection was used to estimate the size of the population in each of these infection classes for different age-groups and calendar years in the Netherlands. Using multiple regression to link these population figures with the information on tuberculosis incidence in the same age group and calendar year, it was possible to estimate the above risks of developing tuberculosis. For Netherlands males aged 15-69 years during the period 1951-70 the three risks of developing pulmonary tuberculosis were estimated to be: (a) 5.06 per cent annually (for 5 years) following primary infection; (b) 1.91 per cent annually (for 5 years) following reinfection; (c) 0.0253 per cent annually, after the first 5 years following primary infection, in the absence of reinfection. The corresponding (and significantly different) estimated annual risks of development of pulmonary tuberculosis for females were 5.85, 1.10 and 0.0020 per cent respectively. From these risks, it may be estimated that the degree of protection conferred by a distant primary infection, against pulmonary tuberculosis arising from a recent reinfection, was 63 per cent for males and 81 per cent for females. The estimated relative proportions of cases of progressive primary, exogenous and endogenous tuberculosis varied considerably with age and calendar year. Progressive primary tuberculosis was dominant at the younger ages, exogenous and endogenous tuberculosis at older ages. At these older ages, the great majority of cases in the Netherlands in the early 1950s appeared to be exogenous in origin, but by 1970, with the decrease in the risk of infection, the exogenous contribution had dwindled substantially, especially among males.
As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis. Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals). Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g. through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.
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OBJECTIVE: To determine the superoxide dismutase (SOD) activity from clinical isolates of Mycobacterium tuberculosis and to study the seroreactivity of SOD from M. tuberculosis H37Rv. DESIGN: Crude cell extracts of 16 strains of M. tuberculosis isolated from tuberculosis (TB) patients were assayed for SOD activity. SOD from H37Rv was partially purified and characterized, and the seroreactivity was studied by ELISA using sera from 36 active pulmonary TB and 31 leprosy patients. RESULTS: SOD activity was detected in all the 16 strains of M. tuberculosis and also in the medium of logarithmic and stationary cultures of H37Rv. SOD activity from H37Rv extract was not affected by 1 mM KCN or by 5 mM H2O2 and was only 20% inhibited by 10 mM NaN3, suggesting that it is a Mn-containing enzyme. SOD was partially purified from H37Rv extract by gel filtration chromatography as a tetramer of molecular weight (MW) of 80,000 and a subunit MW of approximately 23,000. A delayed type hypersensitivity was elicited by SOD in guinea pigs sensitized with H37Rv or M. leprae sonicate. ELISA using SOD as antigen indicated 100% positivity with TB sera, while 84% positivity was observed with leprosy sera. Western blotting with pooled TB and leprosy sera indicated the presence of antibodies to the 23 kD SOD protein. CONCLUSION: Our data indicate that M. tuberculosis strains are rich in SOD, and the secretion of SOD may play a valuable role in the pathogenesis of M. tuberculosis.
Tuberculosis in respiratory system is most common in mycobacterial infections. Eighty percent of the patients with pulmonary tuberculosis visit hospital because of the respiratory symptoms, and only 10% of them were discovered by chest X-ray mass screening. In order to confirm respiratory tuberculosis, various methods to obtain specimens for mycobacterial examination have been carried out; hypertonic saline nebulizing for sputum expectoration, trans-bronchoscopic biopsy, percutaneous needle aspiration, and so on. The recent development of imaging modalities including CT, MRI, and ultrasonogram have been much contributed to the improvement of diagnosis of pleural tuberculosis. Basically, the main treatment for respiratory tuberculosis is chemotherapy except chronic tuberculous thoracic empyema. The initial chemotherapy regimen should be chosen among the three arms; [INH + RFP + PZA + EB (or SM)] x 2-->[INH + RFP] x 6, [INH + RFP + EB (or SM)] x 6-->[INH + RFP] x 3-6, and [INH + RFP] x 6-9. The sputum positive patient is recommended to have the chemotherapy regimen including PZA. In the patients with tracheo-bronchial tuberculosis an attention should be paid for the airway narrowing or obstruction during and after the scheduled chemotherapy. For a part of patients with tuberculous pleurisy and thoracic empyema, a surgical treatment must be indicated.
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A simple and sensitive passive haemagglutination (PHA) test has been evaluated in the serology of human tuberculosis. Double aldehyde stabilized red cells were sensitized with cell extracts and PPD antigens from M. tuberculosis (H37Rv) and used as reagents in the test. The study was conducted on sera from 71 bacteriologically confirmed cases of tuberculosis and their controls, inclusive of 59 healthy blood donors and 28 non-tuberculous chest disease patients. In addition, 318 random samples of sera and 107 finger prick blood samples collected on filter papers from apparently healthy people were examined. For comparative evaluation, tuberculous patients' sera were examined by enzyme linked immunosorbent assay (ELISA) and crossed immunoelectrophoresis (CIE). The distribution of IgG and IgM type antimycobacterial antibodies (AMA) in tuberculous patients' sera was evaluated by a modified PHA test. The results of the study indicated that the PHA test was a sensitive method for the quantitation of antibodies, which could be demonstrated in all groups of sera studied. The PHA test and ELISA with the antigens used were not found to be specific enough for the serodiagnosis of tuberculosis; the results indicated the need to investigate several immunological approaches for this purpose. Both tests did differentiate between the mean AMA levels of tuberculous patients and their controls and both showed treated and relapsed cases of tuberculosis to contain higher serum levels of antibodies than did new cases. Both tests were found to be more sensitive than CIE with the intermediate gel technique. The PHA test was found to be sensitive enough for the measurement of antibodies in finger-prick blood samples, indicating its potential for field studies.
Two hundred and fifty-six sputum, bronchoalveolar lavage, and bronchial and tracheal aspirate specimens from 243 patients were tested for the presence of Mycobacterium tuberculosis complex by auramine fluorochrome staining, rRNA target amplification (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test [AMTD]), and PCR (Roche Amplicor Mycobacterium Tuberculosis Test [Amplicor PCR]. The results were compared with those of conventional Löwenstein-Jensen tube culture and BACTEC radiometric liquid culture. A total of 26 specimens from 18 patients were culture positive for M. tuberculosis. In addition, seven specimens were positive by staining and by culture for other Mycobacterium species but negative by nucleic acid amplification methods and were not included in the comparison. When compared with that for culture, the sensitivities of the techniques were as follows: for staining, 80.8%; for Gen-Probe AMTD, 84.6%; and for Roche Amplicor PCR, 84.6%. The specificities were 99.1, 98.7, and 99.1%, respectively. After resolution of discrepant results by review of the patients' clinical data, 29 specimens from 21 patients were considered positive, and the overall sensitivities, specificities, and positive and negative predictive values were 89.7, 100, 100, and 98.7% for culture; 75.9, 99.5, 95.7, and 96.9% for staining; 86.2, 100, 100, and 98.2% for Gen-Probe AMTD; and 82.8, 100, 100, and 97.9% for Roche Amplicor PCR, respectively. It is concluded that both nucleic acid amplification methods are rapid, sensitive, and specific methods for the detection of M. tuberculosis in respiratory specimens.
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Consensus-based recommendations have been developed by a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis surveillance data in the countries of Europe. A uniform case definition and a minimum set of variables for reporting on each case have been agreed which, when collated on a national basis, will allow comparison of the epidemiology of tuberculosis in different European countries. The Working Group recommends that the case definition includes "definite" cases, where the diagnosis has been confirmed by culture (or supported by microscopy findings in countries where diagnostic culture facilities are not available), and "other than definite cases" based on a clinical diagnosis of tuberculosis combined with the intention to treat with a full course of antituberculosis therapy. Both "definite" and "other than definite" cases should be notified by physicians and, in addition, laboratories should be required to report "definite" cases. The minimum set of variables to be collected on each case of tuberculosis should include: date of starting treatment, place of residence, date of birth, gender, and country of origin, to characterize the patient. Recommended disease-specific variables include: site of disease, bacteriological status (microscopy and culture), and history of previous antituberculosis chemotherapy. The minimum set of variables should be collated on all patients and should be as complete as possible. Additional variables may be collected for individual, local or national purposes, but, in general, completeness of reporting on cases is likely to be better if the information requested is kept to a minimum. Timely reporting of cases is essential for appropriate public health action. Cases should be reported to the health authority at the local and/or regional level within 1 week of starting treatment. Individual-case based information should be reported to the national level by the local or regional level. Feedback to reporters is essential. At the national level, preliminary quarterly reports should be produced and final reports should be published annually.
The results of 22.218 respiratory specimens sent to our laboratory were studied to determine the sensitivity of the Ziehl-Neelsen (Z-N) stain and microscopy-fluorescence method for detection of M.tbc and MOTT. There were no AIDS patients among analyzed cases. Smears were positive for acid fast bacilli (AFB) 60.0% (480 of 800) of specimens growing M. tuberculosis and 25.1% (219 of 872) of specimens growing the six common species of MOTT. Smear positivity by species was 28.1% (141 of 502) for M. kansasii, 29.4% (43 of 146) for MAIC, 28.7% (35 of 122) for M. xenopi. No smear was positive for M. gordone (43 cultures), M. fortuitum (33 cultures), M. scrofulaceum (26 cultures). The rate of nonculturable mycobacteria on L-J medium was 0.2%; mean rate of contamination was 4.6%. We also analyzed the relation between the number of AFB seen on the smear and time of the growth of M. tuberculosis and relation between abundance of the culture growth and AFB seen on smears. These study suggest that the sensitivity of microscopy for Mycobacterium tuberculosis is comparable with the data of others authors. Sensitivity of microscopy is lower in MOTT detection than for M.tbc (p < 0.001). Time of growth and abundance of the M. tuberculosis cultures were adequate to AFB seen in microscopy.
Two patients with rare localizations of extrapulmonary tuberculosis are presented. In a 55-year-old man admitted with septic fever and a low neutrophil count, ultrasonography of the spleen revealed splenomegaly with numerous hypodense foci. Fine needle biopsy of one of the foci disclosed tuberculosis. Persistent splenogenic neutropenia and thrombocytopenia, despite tuberculostatic therapy, required splenectomy which confirmed the initial diagnosis. At laparotomy no other abdominal foci of tuberculosis were found. In a second 57-year-old man admitted for ascites and weight loss, a biopsy specimen of the liver showed normal liver parenchyma but, by chance, peritoneal tuberculosis. Tuberculostatic therapy brought about cure.
This consensus statement is prepared primarily as a concise reference for tuberculosis chemotherapy in Hong Kong. Treatment should be tailored to patients individually, expert advice should be sought when necessary, and 'directly observed treatment' should be used where possible. A 6-month regimen is recommended as the initial treatment of uncomplicated pulmonary tuberculosis and a 9-month regimen is recommended for retreatment. Patients with disease that is resistant to isoniazid or rifampicin may require modified regimens. Multidrug-resistant tuberculosis should be managed in specialised centres, using multiple drugs as guided by in vitro susceptibility tests. Recommended regimens to treat extrapulmonary tuberculosis are based on limited current evidence, although shorter regimens may be acceptable when better evidence emerges. A longer duration of treatment is required for diabetic, immuno-compromised, or silicotic patients. During pregnancy, streptomycin should be avoided; the safety profiles of second-line drugs have not yet been ascertained. Hepatotoxic drugs should be used with caution in patients with liver dysfunction, and extra caution and dosage reductions are required if streptomycin and ethambutol are used in patients with renal impairment.