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[Controlled clinical trial on efficacy of 5-month regimens and whole course intermittent 6-month regimens in treating bacillary pulmonary tuberculosis].

OBJECTIVE: To assess the therapeutic efficacy of rifapentine (L), to reduce the duration of treatment and the frequency of drug administration, and to observe the influence on efficacy and adverse reactions of using pyrazinamide (Z) through whole-course. METHOD: Two 5-month regimens respectively including rifampin (R) and L and two whole course intermittent regimens were designed as following: I: 2SHRZ/3R2H2Z2; II: 2SHRZ/3L1H2Z2; III: 2S3H3R3Z3/4L1H2Z2; IV: 2S3H3R3Z3/4L1H2E2. A total of 366 newly-diagnosed bacillary pulmonary tuberculosis patients were admitted and randomly allocated. RESULTS: 339 cases completed the prescribed short course chemotherapy. The sputum conversion rates at the end of the treatment of groups I, II, III and IV were 97.0%, 94.1%, 100.0% and 97.2% respectively. X-ray resolution rates were 96.0%, 97.6%, 100.0% and 94.4% respectively. Cavity-close rates of the 5-month regimens and the 6-month regimens were 77% and 76%. Comparing the results among groups, there were no statistically significant differences (P > 0.05), and no obvious side-effect was found. 305 patients have been followed up for 3 years since completion of the chemotherapy. The bacteriological relapse and bacteriological relapse with deterioration on chest X-ray in groups I, II, III and IV were seen in 2,3,6 and 3 cases respectively. CONCLUSION: Domestic-made rifapentine is a long-acting, highly effective antituberculosis drug. It is unnecessary to use Z in continuation phase, and it is possible to shorten the duration to 5 months with the appropriate combination of essential drugs, which is worthwhile for further study.

Antitubercular Agents↗

Comparative study on the immunogenicity between Hsp70 DNA vaccine and Hsp65 DNA vaccine in human Mycobacterium tuberculosis.

The BALB/c mice were immunized with Hsp70 DNA and Hsp65 DNA vaccines in human Mycobacterium tuberculosis. Eight weeks after immunization, the eyeballs were removed, blood and spleen taken, and intraperitoneal macrophages were harvested. The lymphocytic stimulating index (SI) was used to measure the cellular proliferating ability and NO release to measure the phagocytic activity of the macrophages. With ELISA kit, the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in serum and the splenic lymphocytic cultured supernatant were detected. The results showed that after the mice were immunized with 100 micrograms/mouse of Hsp70 DNA vaccine intramuscularly, the splenic lymphocytic proliferating ability in the mice was significantly increased as compared with that in the control group, vector group and Hsp65 DNA vaccine group (P < 0.01); The contents of NO in the intraperitoneal macrophages of the mice were significantly lower than in the control group and Hsp65 DNA vaccine group (P < 0.01); The levels of serum IL-2 in the mice were significantly higher than in the control group, but there was no statistical difference between Hsp65 DNA group and vector group (P > 0.05); The contents of serum IFN-gamma in the mice were significantly higher than in the control group, but significantly lower than in the Hsp65 DNA vaccine group (P < 0.05). It was indicated that immunization with Hsp70 DNA vaccine could obviously enhance the immune response, but its intensity seemed inferior to Hsp65 DNA vaccine. The anti-infection mechanisms and clinical use in the future of the vaccines of Hsp70 DNA and Hsp65 DNA are worth further studying.

Animals↗

[Frequent return as a novel strategy for tuberculosis treatment adherence].

OBJECTIVE: Treatment dropout is one of the major obstacles to the control of tuberculosis. The aim of the present study was to evaluate the frequent return strategy instituted at the Tuberculosis Control Program, as well as the program as a whole, identifying and quantifying potential risk factors for dropout. METHODS: The present study was conducted in Ubatuba, Southeastern Brazil. All patients (n=244) notified by the Tuberculosis Control Program in the two years preceding and the two years following the introduction of the frequent return strategy in 1999 were included. We carried out a descriptive analysis of the data and analyzed treatment results and program evaluation indicators. We performed univariate and multivariate analysis in order to identify potential risk factors associated with dropout. We also analyzed the frequent return strategy using chi-squared tests. RESULTS: The strategy reduced the risk of treatment dropout from 12.3% to 4.9%. Risk factors associated with dropout were lack of schooling (OR=3.01; p=0.051), unemployment (OR=3.36; p=0.046), and alcohol dependence (OR=3.56; p=0.014). CONCLUSIONS: The frequent return strategy reduced the risk of treatment dropout, although results did not reach statistical significance due to the small number of dropouts. This strategy may be an alternative for the supervised treatment for all patients recommended by the World Health Organization.

Adolescent↗

Analysis of circulating immune complexes (CIC) in tuberculosis: levels of specific antibody and antigens in CIC and relationship with serum antibody.

Eighty sera from tuberculosis (TB) patients, 16 Indian and 10 American control sera were analyzed by ELISA for relative titres of antibody against mycobacterial antigens. Levels of specific antibody and mycobacterial Ag in circulating immune complexes (CIC) isolated from these sera were also studied. All these parameters were found to be elevated in TB sera as compared to control sera. Maximum increase was however noted in CIC specific antibody titres. A good correlation was observed between serum and CIC levels of specific antibody (r = 0.72) and between specific antigen (Ag) and antibody (Ab) levels within CIC (r = 0.64). In a few of the TB sera examined, CIC specific Ab contributed less than 1% to the Ab titres in sera. In order to examine the differences between different subgroups within TB patients, a statistical analysis of variance was performed. Sex of the patients had no effect on any parameter. Sputum-positive patients had significantly higher levels of CIC Ag and Ab than the sputum-negative patients, although no significant difference occurred in respect to serum Ab. All three parameters were significantly higher in patients on chemotherapy as compared to fresh untreated cases. The relevance of these observations to the development of a CIC-based immunodiagnostic assay for TB is discussed.

Analysis of Variance↗

Evaluation of new external quality assessment guidelines involving random blinded rechecking of acid-fast bacilli smears in a pilot project setting in Mexico.

SETTING: Laboratories in Mexico that support the national tuberculosis (TB) control program have been involved in an acid-fast bacilli (AFB) microscopy external quality assurance program which includes rechecking 100% of smears identified as AFB-positive by the local laboratories and 10% of smears identified as AFB-negative. Very few errors have been detected in Mexico using non-random selection and unblinded rechecking of the slides. OBJECTIVE: To evaluate the results from a 1-year pilot program involving blinded rechecking of randomly selected AFB slides from local TB laboratories in two Mexican states and determine its feasibility for future implementation. DESIGN: To reduce potential bias, laboratory staff from the National TB Laboratory, Institute for Epidemiological Diagnosis and Reference (InDRE), performed quarterly statistical sampling of AFB smears and on-site evaluations in local laboratories in each state. AFB smears were rechecked at the respective state laboratories with discordant results resolved at InDRE. RESULTS: A significantly greater percentage of errors was detected on the randomly selected, blinded AFB smears than on the non-randomly selected, unblinded smears. CONCLUSION: Random blinded rechecking provides more accurate estimates of AFB microscopy results, resulting in improved diagnosis and monitoring of treatment response.

Bacteriological Techniques↗

[Tuberculosis control in Kobe City--analyses of advisory contents and disqualified cases by integrated tuberculosis advisory committee].

The incidence of tuberculosis (TB) in Kobe City has been higher in comparison with that of Japan, thereby Kobe City ought to enforce anti-tuberculosis activities. Nine Wards public health departments of Kobe City used to convene their own tuberculosis advisory committees until April 1998, when a centralized committee was established to examine all TB patients. The new committee was authorized to issue clinical advice to registered physicians whenever necessary in order to improve treatment standard of TB. The author analyzed the contents of issued documents and observed any change in statistics before and after establishment of the committee. During the past 3 years, the new committee had sent 2,221 advisory documents to physicians, which occupied 35% of all 6,305 applied cases. Main suggestions included proper choice of anti-tuberculosis agents, adequate duration of treatment and reference to the results of laboratory examinations. In addition, 140 cases were rejected for medical expenses subsidy by TB Law to avoid unnecessary long-term treatment. Main reasons of rejection were long-term treatment despite negative bacilli too more than one year, continuous single INH administration following the completion of the standard treatment and unnecessary treatment for the cases with inactive findings on chest X-ray. Since the establishment of the integrated committee, the statistics of TB has demonstrated a significant decrease in the incidence and the prevalence of TB with its annual reduction of 5.6, and 11.5 per 100,000 respectively. The proportion of bacteriologically confirmed cases among newly registered patients has increased, and the diagnostic accuracy was improved due to the decrease in the unknown bacteriology case. The proportion of the case treated by INH alone fall down rapidly and it is lower than that of the whole country. These data demonstrate that the integrated tuberculosis advisory committee contributes to standardize anti-tubercular treatment through dissemination of proper guidance on TB diagnosis and treatment to all medical facilities in the city.

Advisory Committees↗

Tuberculosis treatment delivery in high burden settings: does patient choice of supervision matter?

SETTING: The Northern Cape Province, Republic of South Africa. OBJECTIVES: To determine the effect of patient choice of treatment delivery option on the treatment outcomes of tuberculosis (TB) patients in a high burden setting under actual programme conditions. DESIGN: Cohort study involving 769 new and retreatment TB patients recruited from 45 randomly selected clinics. Patients were interviewed and subsequent follow-up was done through regular visits to the clinics to check progress through formal health records. RESULTS: There was a statistically significant difference (P < 0.001) between the treatment outcome of new patients (70% successful) and re-treatment patients (54% successful). Direct observation of treatment (DOT) was found to have no effect on the treatment outcome of new patients (P = 0.875), but re-treatment patients were found to fare better with than without DOT (OR 14.2, 95% CI 4.18-53.14, P < 0.001). CONCLUSION: The results obtained for new patients are similar to those of two recent randomised controlled trials on DOT. This study revealed that for new patients, undue emphasis on universal DOT might be unnecessary. It would perhaps be more beneficial to target supervision at those patients who are most likely to benefit from it (i.e., re-treatment patients). This is of particular relevance in high burden, resource-limited settings where universal DOT for all TB patients is generally unfeasible.

Adolescent↗

Impact of BCG vaccination on tuberculin surveys to estimate the annual risk of tuberculosis infection in south India.

BACKGROUND AND OBJECTIVES: Annual risk of tuberculosis infection (ARTI) computed from prevalence of infection measures the extent of tuberculosis transmission in the community and it is used to monitor the tuberculosis control programme. This is usually derived from tuberculin surveys among children not vaccinated with BCG. This study explores whether the estimated ARTI among BCG vaccinated children is comparable to that of unvaccinated children. METHODS: Three tuberculin surveys were undertaken among children aged >10 yr as part of assessing the impact of DOTS implemented in Tiruvallur district, south India. The prevalence of infection was estimated using the anti-mode method among vaccinated and unvaccinated children. The ARTI was computed separately and compared in all the three surveys. RESULTS: The prevalence of infection among unvaccinated and vaccinated children in the first survey were 7.8 per cent (95% CI: 7.1-8.6) and 7.9 per cent (95% CI: 7.1-8.8) respectively (ARTI was estimated to be 1.6 per cent in both groups) and the difference was not statistically significant. The corresponding figures for children test read in the second and third surveys were 6.9 per cent (95% CI: 6.2-7.6) and 6.8 per cent (6.0-7.5) and; 6.0 per cent (5.2-6.7) and 6.0 per cent (5.5-6.5) respectively. The computed ARTI was respectively 1.4 and 1.2 per cent among unvaccinated children in the second and third surveys; and 1.4 and 1.2 per cent among vaccinated children in the second and third rounds. INTERPRETATION AND CONCLUSION: There was no difference in the infection with Mycobacterium tuberculosis among vaccinated and unvaccinated children. BCG vaccinated children may thus be included for estimation of infection to assess the extent of transmission in the community as well as for monitoring purpose.

Adolescent↗

Interventions for treating tuberculous pericarditis.

BACKGROUND: Tuberculous (TB) pericarditis is becoming more common. The infection can result in fluid around the heart, which can be fatal. OBJECTIVES: To evaluate evidence from trials about the effects of medical and surgical treatments for TB pericarditis on death and life-threatening conditions. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane controlled trials register, Medline, Embase and reference lists of articles; contact with experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of treatments for TB pericarditis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Meta-analysis using fixed effects models calculated summary statistics, provided there was no significant heterogeneity, and expressed results as relative risk. MAIN RESULTS: Three trials met the inclusion criteria, with a total of 411 participants. Treatments were adjuvant steroids and surgical drainage. Two small trials tested steroids. There were fewer deaths (all causes) in the intervention group, but the numbers were small and the result could have occurred by chance (relative risk [RR] 0.65, 95% confidence interval [CI] 0.36 to 1.16, n = 350). In one trial studying patients with effusion, "cure" was higher in the steroid group (alive and free of disability at 2 years (RR 0.69, 95% CI 0.29 to 0.80, n = 221). One trial examined open surgical drainage compared with conservative management, and showed no impact of surgery on death, but a protective effective against cadiac tamponade (RR 0.04, 95% CI 0.00 to 0.64). REVIEWER'S CONCLUSIONS: Steroids have potentially large impacts on survival, but trials are too small to test this. We believe further placebo controlled trials of steroids are warranted, exploring whether the presence of effusion or fibrosis modifies effects. Surgical options also require further evaluation.

Adrenal Cortex Hormones↗

Association of conversion & cure with initial smear grading among new smear positive pulmonary tuberculosis patients treated with Category I regimen.

BACKGROUND & OBJECTIVES: Early diagnosis of tuberculosis (TB) is important for initiating treatment to gain cure. The present investigation was undertaken to study the association of conversion and cure with initial smear grading among pulmonary tuberculosis (TB) patients registered in a directly observed treatment - short course (DOTS) programme in Tiruvallur district, south India. METHODS: All new smear positive cases registered from May, 1999 to December, 2002 were analysed for conversion and cure related to initial smear grading. RESULTS: Of the 1463 patients, 1206(82.4%) were converted at the end of the intensive phase and 1109 (75.8%) were declared 'cured' after the completion of treatment. The cure rate decreased as the initial smear grading increased and the decrease in trend was statistically significant (P=0.01). Similarly, a significant decrease in conversion rate was also observed with increase in initial smear grading (P<0.001). In multivariate analysis, lower cure rate was significantly associated with patient's age (AOR=1.5, 95% CI=1.1-2.1), alcoholism (AOR=1.7, 95% CI 1.2- 2.4) and conversion at the end of intensive phase (AOR=3.5, 95% CI= 2.6-4.8). INTERPRETATION & CONCLUSION: Cure and conversion rates were linearly associated with initial smear grading. High default and death rates were responsible for low cure and conversion. The proportion of patients who required extension of treatment and those who had an unfavourable treatment outcome were significantly higher among patients with a 3+ initial smear grading. This reiterates the need to pay more attention in motivating these patients to return to regular treatment and sustained commitment in the control of tuberculosis. There is a need to extend the treatment for one more month in the intensive phase of treatment.

Adult↗

Controlled comparison of BACTEC 13A, MYCO/F LYTIC, BacT/ALERT MB, and ISOLATOR 10 systems for detection of mycobacteremia.

To compare the performance of the BACTEC 13A (Becton Dickinson, Sparks, Md.), BACTEC MYCO/F LYTIC (Becton Dickinson), BacT/ALERT MB (bioMérieux, Durham, N.C.), and ISOLATOR 10 lysis-centrifugation (Wampole Laboratories, Cranbury, N.J.) systems for detection of mycobacteremia in adults, we inoculated 5-ml aliquots of blood from patients with suspected mycobacteremia into the bottle or tube required for each system. Of 600 sets tested, 85 (14%) yielded Mycobacterium avium complex (MAC) and 9 (2%) yielded other species of mycobacteria. Of 26 complete (three bottles and one tube) adequately filled (5 +/- 1 ml) sets from which MAC was recovered, BACTEC 13A was positive for 19 (73%), BACTEC MYCO/F LYTIC was positive for 21 (81%), BacT/ALERT MB was positive for 22 (85%), and ISOLATOR 10 was positive for 21 (81%). Of the six possible two-way comparisons, the mean times to detection for the recovery of MAC from each bottle in positive adequately paired sets were 15.3 days for BACTEC 13A versus 12.8 days for MYCO/F LYTIC for 33 of 340 pairs, 14.1 days for BACTEC 13A versus 11.6 days for BacT/ALERT MB for 38 of 380 pairs, 12.6 days for BACTEC 13A versus 20.0 days for ISOLATOR 10 for 26 of 261 pairs, 12.8 days for BACTEC MYCO/F LYTIC versus 11.0 days for BacT/ALERT MB for 33 of 340 pairs, 13.2 days for BACTEC MYCO/F LYTIC versus 20.4 days for ISOLATOR 10 for 24 of 230 pairs, and 9.9 days for BacT/ALERT MB versus 19.0 days for ISOLATOR 10 for 24 of 257 pairs. There were no significant differences in yields between the systems. However, the mean time to detection differed significantly among the systems. The time to detection was shortest for BacT/ALERT MB, followed by BACTEC MYCO/F LYTIC and BACTEC 13A and then ISOLATOR 10. Although the numbers were too small for statistical comparison, the time to detection was substantially shorter for MAC than for Mycobacterium tuberculosis complex in the liquid systems. The continuously monitored systems (BACTEC MYCO/F LYTIC and BacT/ALERT MB) were as sensitive and, on balance, faster for the detection of MAC bacteremia than were the heretofore standard manual ISOLATOR 10 and radiometric BACTEC 13A systems.

AIDS-Related Opportunistic Infections↗

Smoking and tuberculosis among the elderly in Hong Kong.

A cohort of 42,655 clients that were first registered with the Elderly Health Service in 2000 were followed prospectively through the tuberculosis (TB) notification registry until the end of 2002. A total of 286 active TB cases (186 culture confirmed) were identified. The annual TB notification rates were 735, 427, and 174 per 100,000 among current smokers, ex-smokers, and never-smokers, respectively (p < 0.001). The trend in TB risk persisted after the control of background characteristics using Cox proportional hazards analysis (adjusted hazard ratios [HRs]: 2.63, 1.41, and 1, p < 0.001). In comparison with never-smokers, current smokers had an excess risk of pulmonary TB (adjusted HR, 2.87; 95% confidence interval [CI], 2.00-4.11; p < 0.001), but not extrapulmonary TB (adjusted HR, 1.04; 95% CI, 0.33-3.30; p = 0.95). Among the current smokers, those who developed TB smoked more cigarettes per day than those who did not (13.43, SD 8.76 vs. 10.96, SD 7.87, p = 0.01). A statistically significant dose-response relationship was observed with respect to active TB and culture-confirmed TB (both p < 0.05). Smoking accounted for 32.8% (95% CI, 14.9-48.0%), 8.6% (95% CI, 3.3-15.1%), and 18.7% (95% CI, 7.7-30.4%) of the TB risk among males, females, and the entire cohort, respectively. Approximately 44.9% (95% CI, 20.7-64.6%) of the sex difference was attributable to smoking.

Aged↗

Allergen-induced proliferation and interleukin-5 production by bronchoalveolar lavage and blood T cells after segmental allergen challenge.

In order to detect and characterize allergen-specific T cells in the airways of atopic asthmatics, we measured proliferation and cytokine production by bronchoalveolar lavage (BAL) T cells isolated from Dermatophagoides pteronyssinus (Der p)-sensitive asthmatics and nonatopic control subjects, and compared the results with those generated using peripheral blood (PB) T cells. BAL and PB mononuclear cells were collected 24 h after segmental allergen challenge by fibreoptic bronchoscopy and venepuncture, respectively. T cells purified from BAL and PB were stimulated with autologous, irradiated antigen-presenting cells and D. pteronyssinus extract or a control, nonallergen antigen (M. tuberculosis purified protein derivative [PPD]). IL-5 and IFN-gamma concentrations were measured in culture supernatants by ELISA, and T-cell proliferation by 3H-thymidine uptake. D. pteronyssinus-induced proliferation of T cells derived from both BAL and PB was elevated in asthmatics when compared with control subjects (p < 0.05), whereas PPD-induced proliferation was equivalent in both compartments. In the asthmatics, D. pteronyssinus-induced proliferative responses of equivalent numbers of BAL and PB T cells obtained after allergen challenge were statistically equivalent. Nevertheless, BAL T cells stimulated with D. pteronyssinus produced significantly greater amounts of IL-5 than did PB T cells (p < 0.05). Allergen-induced proliferation and IL-5 production by BAL T cells in the asthmatics after segmental allergen challenge correlated with the percentages of eosinophils in the BAL fluid (p < 0.01). Further, BAL T cells from asthmatic patients produced significantly higher amounts of IL-5 than did the same number of cells from nonatopic control subjects (p < 0.05). We conclude that, in D. pteronyssinus-sensitive asthmatics, allergen-specific T cells can be detected in the bronchial lumen after allergen challenge and that allergen-induced proliferation and IL-5 production by these cells correlates with local eosinophil influx. Although bronchial luminal T cells show an equivalent proliferative response to allergen stimulation as compared with PB T cells, they do produce more IL-5, consistent with the hypothesis that local differentiation or priming of these cells within the bronchial mucosal environment results in upregulation of allergen-induced IL-5 secretion.

Adult↗

Lymphocyte proliferative response and subset profiles during extended periods of chloroquine or primaquine prophylaxis.

Immune suppression and disturbances of normal leukocyte populations are side effects attributed to many antimalarial drugs and were concerns during a recent year-long placebo-controlled trial that compared daily primaquine (0.5 mg of base per kg of body weight per day) with weekly chloroquine (300 mg of base one time per week) for malaria prophylaxis. The study took place in Irian Jaya, Indonesia, from July 1994 to August 1995 and enrolled 129 Javanese men with normal glucose-6-phosphate dehydrogenase function. Tests for lymphocyte function and subset composition were conducted blindly on a cross-section of subjects during weeks 10 (n = 42) and 48 (n = 72) of supervised prophylaxis. Lymphocyte function, measured as the proliferative response of peripheral blood mononuclear cells to a panel of mitogens (pokeweed mitogen, phytohemagglutinin, and concanavalin A) and antigens (purified protein derivative of Mycobacterium tuberculosis and Clostridium tetani toxoid) and expressed as a stimulation index, allowed for statistical comparison between groups and sampling times. The lymphocyte subset composition for each group and time point was based on flow cytometry profiling, and the results were expressed as the mean percentages of CD3 (total T cells), CD19 (total B cells), CD4+ (T-helper and inducer cells), and CD8+ (T suppressor and cytotoxic cells), CD3/CD16+ CD56 (natural killer cells), CD3/anti-HLA-DR (activated T cells) cells and the CD4+/CD8+ ratios. Lymphocyte stimulation indices were statistically comparable among the placebo, primaquine, and chloroquine groups at both time points, although the primaquine group was distinguished by having repeatedly greater proportions of subjects with high ( > 3.0) stimulation indices. The lymphocyte subset profiles of these groups at both time points were also similar and undistorted relative to those of healthy reference populations matched for age, sex, and ethnicity. The results provide quantitative support for the safety of daily primaquine prophylaxis.

Adult↗

Clinical trial of two short-course (6-month) regimens and a standard regimen (12-month) chemotherapy in retreatment of pulmonary tuberculosis in Pakistan. Results 18 months after completion of treatment (Lahore Tuberculosis Study).

This study compared the efficacy and tolerability of two 6-month daily regimens of isoniazid and rifampin in combination with either pyrazinamide or ethambutol (RHZ and RHE regimens) against a standard daily regimen of streptomycin, isoniazid, and ethambutol (SHE regimen) given for 6 months followed by isoniazid and ethambutol for an additional 6 months. Only previously treated sputum positive patients suffering from active pulmonary tuberculosis were entered into the study. Three hundred and fifty-eight patients were admitted to the study and 267 (75%) completed chemotherapy. Eighty-five percent of RHZ-regimen and 82% of RHE-regimen patients achieved sputum culture negativity compared to 55% of patients in SHE regimen. Successfully treated patients were followed up for 18 months, and among these, all 3 treatment regimens showed broadly similar levels of culture negativity at the end of the follow-up period. Final therapeutic outcome was based on sputum culture results obtained throughout the follow-up period, and no statistically significant difference in relapse rate was noticed in the 3 regimens. Severe drug intolerance necessitated discontinuation of therapy in only 2 patients.

Antitubercular Agents↗

Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients.

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.

AIDS-Related Opportunistic Infections↗

The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis.

OBJECTIVES: To investigate HLA-DRB1, DQA1 and DQB1 allelic polymorphism in Iranian patients with pulmonary tuberculosis (PTB). METHODS: Forty patients with smear-positive PTB and 100 healthy individuals as a control group were studied for MHC class II allelic polymorphism by polymerase chain reaction with sequence-specific primers (PCR-SSP). The primer was supplied by biotest in the standard kit. DRB low resolution SSP and DQA, DQB intermediate resolution SSP was applied. RESULTS: The comparison of the patients and the control group showed a significant increase in the frequency of the HLA-DRB1*07 and DQA1*0101 alleles (OR 2.7, 95%CI 1.19-6.13, P = 0.025 and OR 2.66, 95%CI 1.15-6.44, P = 0.04, respectively) in the patient group. The frequency of DQA1*0301 and DQA1*0501 was also significantly decreased (OR 0.254, 95%CI 0.075-0.865, P = 0.033 and OR 0.53, 95%CI 0.3-0.95, P = 0.045, respectively) in the PTB patients. Concerning haplotype frequency, DRB1*11501, QDQA1*0103 and DQB1*0601 were increased, but this difference was not statistically significant. In the DQB1 locus, DQB1*0501 was non-significantly over-represented. CONCLUSIONS: HLA-DRB1*07 and HLA-DQA1*0101 appeared to be the predisposing alleles and HLA-DQA1*0301 and 0501 the protective alleles in our patients with TB.

Aged↗

Tuberculosis treatment default at the communicable diseases unit of Effia-Nkwanta Regional Hospital: a 2-year experience.

SETTING: Effia-Nkwanta Regional Hospital, located at Sekondi-Takoradi, the capital and third largest city of the Western Region of Ghana. OBJECTIVE: To examine factors associated with treatment default among tuberculosis (TB) patients registered for treatment in 2000-2001. DESIGN: Retrospective review of institutional records of TB patients. METHOD: The database for registered TB patients was sorted out into the six treatment outcomes. Five outcomes were combined into one variable named 'non-defaulters' and were compared with defaulters. Statistical significance was taken as P < 0.05. RESULTS: The defaulter rate for all categories of patients was 13.9%. Default from treatment was significantly associated with male sex, smear positivity and living in communities far from the treatment centre. Patients in the 25-44 year age group and those put on the retreatment regimen have higher defaulter rates, but these were not statistically significant when compared to non-defaulters. The mean defaulting moment was 3.4 months. The overall probability of a patient remaining on treatment 5 months after starting was 3.6%. CONCLUSION: Treatment centres should be sited near the patients to improve access. Further studies are needed to identify the barriers for patients in completing their treatment.

Adolescent↗