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[Genital tuberculosis in African female patients (author's transl)].

Genital tuberculosis in 76 Senegalese women and 82 Nigerian women, have been compiled from statistical tables covering a period of 10 years. The authors present the features of genital tuberculosis in african females. In most cases, diagnosis is made through peroperative findings or anatomo-pathological control of exeresis specimens; still, biopsy of endometrium, systematically performed on each patient consulting for sterility, gave opportunity to detect an important number of cases of genital tuberculosis in Nigeria. The frequency of this disease is low among other unspecific genital infections. Its medical treatment is effective on tuberculous infection but not on sterility which is an unavoidable sequella.

Adolescent↗

[Pulmonary tuberculosis and diabetes mellitus--report of the 29th B series of controlled trials of chemotherapy. Cooperative Study Unit of Chemotherapy of Tuberculosis of National Sanatoria in Japan (CSUCTNS)].

The data obtained from 315 cases of pulmonary tuberculosis with positive sputum and complicated with diabetes mellitus were collected and the results were summarized as follows; 1) Patients were collected from admitted patients in 1983. 2) Ratio of male to female was 3.3 to 1. 3) Most patients (80.1%) were in the age groups over 50. 4) Patients were divided into two groups according to the degree of control of diabetes: one group was well controlled and the other was not. Bacilli negative conversion rate was 98.4% in the well controlled group and 91.6% in the other group at 6 months, and the difference was statistically significant.

Adult↗

Recent bioequivalence studies on fixed-dose combination anti-tuberculosis drug formulations available on the global market.

SETTING: Concern has been expressed about the bioavailability of rifampicin in some fixed-dose combination (FDC) anti-tuberculosis formulations. OBJECTIVE: To evaluate the relative bioavailability of rifampicin in various FDC formulations currently in use in tuberculosis control programmes in the global market. DESIGN: A two-period randomised crossover bioequivalence study in healthy male volunteers, with a 1 week washout period between treatments. Plasma rifampicin concentrations were measured at 0, 1, 2, 4, 6, 8 and 12 hours after each drug administration. RESULTS: The AUC0-8, AUC0-12 and Cmax for rifampicin in seven of 10 FDC formulations was not found to be bioequivalent to the reference administered as loose (separate) formulations. This was confirmed using parametric and non-parametric statistical methods. CONCLUSIONS: The poor relative bioavailability of rifampicin from some FDCs has been documented. The implications for tuberculosis programmes are extremely serious and warrant urgent attention.

Antibiotics, Antitubercular↗

Surveillance and risk management during the latter stages of eradication: experiences from Australia.

The paper reviews the eradication of bovine tuberculosis from Australia with special reference to surveillance and managing the risk of animals exposed to tuberculosis infected animals during the latter stages of eradication. The successful eradication was based on a sound technical program with strong industry and government support. The model of joint industry and government funding and decision-making first used during the brucellosis and tuberculosis eradication campaign (BTEC) has been successfully incorporated within subsequent livestock disease control programs in Australia. An overview of the history of tuberculosis eradication in Australia provides a background to the surveillance approach. Australia was fortunate that there were no wildlife reservoir hosts. Feral animal reservoir hosts were removed during the eradication program. Surveillance to detect rare diseases is recognised to be statistically challenging with high resource requirements. Australian veterinary authorities have a high level of confidence that the combination of increasing sensitivity of abattoir surveillance systems by the submission of all granulomas detected at slaughter with increasing risk management of animals exposed to tuberculosis infected animals during the final stages of eradication provides a high level of assurance that Mycobacterium bovis has been eradicated.

Animals↗

Analysis of whole-genome microarray replicates using mixed models.

MOTIVATION: Microarray experiments are inherently noisy. Replication is the key to estimating realistic fold-changes despite such noise. In the analysis of the various sources of noise the dependency structure of the replication needs to be taken into account. RESULTS: We analyzed replicate data sets from a Mycobacterium tuberculosis trcS mutant in order to identify differentially expressed genes and suggest new methods for filtering and normalizing raw array data and for imputing missing values. Mixed ANOVA models are applied to quantify the various sources of error. Such analysis also allows us to determine the optimal number of samples and arrays. Significance values for differential expression are obtained by a hierarchical bootstrapping scheme on scaled residuals. Four highly upregulated genes, including bfrB, were analyzed further. We observed an artefact, where transcriptional readthrough from these genes led to apparent upregulation of adjacent genes. AVAILABILITY: All methods and data discussed are available in the package YASMAhttp://www.cryst.bbk.ac.uk/wernisch/yasma.html for the statistical data analysis system R (http://www.R-project.org).

Algorithms↗

Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis: clinical and possible pathogenic significance.

A statistically highly significant elevation of serum ACE was found in a group of 58 patients with sarcoidosis (serum ACE was elevated in 34% of patients), as compared with normal controls and patients with tuberculosis and various other common diseases. The results suggest that serum ACE is a useful aid for the diagnosis of sarcoidosis when elevated, but that a normal value does not rule out the condition and may occur in more than one-half of monitored patients. There is a trend to diminution of serum ACE with increasing duration of disease with or without steroid therapy, perhaps correlating with the total body mass of active granulomas, as indirectly suggested in preliminary data by correlation of serum ACE with serum globulin in 16 sarcoidosis patients. It is not yet clear whether there is any significant steroid effect on serum ACE, but a significant number of patients on steroid therapy for more than 2-4 yr have elevated serum ACE values, which in some instances are extremely high. There was a 12-fold elevation in ACE to specific activities generally exceeding those of normal lung in granulomatous lymph nodes of 14 patients with sarcoidosis, suggesting that sarcoid granulomas may be actively synthesizing ACE and resulting in elevation of serum ACE. Extensively fibrotic sarcoid lymph nodes had normal or slightly elevated ACE, suggesting that obliteration of granulomas in sarcoid lymph nodes diminishes their ACE content and that this obliteration may be related to the tendency to diminution of serum ACE with time. ACE was not elevated in one tuberculous lymph node or in experimental granulomas, suggesting that elevation of ACE may have some specificity for the granuloma of sarcoidosis rather than being a characteristic of all granulomas. The catalytic and physical properties of ACE in serum and lymph nodes in sarcoidosis were generally similar to normal ACE with respect to pH activity, modulators, polyacrylamide-gel electrophoresis, and Sephadex G-200 gel filtration. However, sarcoid lymph node ACE appeared to be more heat labile than normal lung or lymph node ACE, suggesting the possibility that an abnormal ACE may be present in sarcoidosis. If an abnormal enzyme is indeed present, it might be coded for by a host gene that is not normally expressed or a nonhost gene or it might be a normal ACE that has been altered. No ACE activity was found in circulating white blood cells in sarcoidosis or in control subjects, suggesting that circulating white blood cells may not contain the epithelioid cell precursor or that ACE synthesis (or less likely, uptake) may be turned on at a later stage in the transformation. Lysozyme activity was also elevated in sarcoid lymph nodes. Serum ACE and serum lysozyme were significantly positively correlated in 16 sarcoidosis patients, suggesting a relationship between the two...

Granuloma↗

Mycobacterium tuberculosis antigen, interleukin 2 and interleukin 2 inhibitor in patients with rheumatoid arthritis.

IL-2 production by the phytohemaglutinin (PHA)-stimulated mononuclear cells (MNC) of peripheral blood (PB) and synovial fluid (SF) from patients with rheumatoid arthritis (RA), other arthritic diseases (OAD) and age-matched normal controls were studied, and the activity of IL-2 inhibitor in sera of studied subject was examined. The significant decreased IL-2 production by PB MNC from the patients with RA (p < 0.05) and OAD (p < 0.05) were observed when compared with normal controls, and no statistical difference was found although IL-2 levels in RA PB were lower than in OAD PB. However, significant statistical difference (p < 0.01) was found when the IL-2 production by RA SF was compared with OAD SF. Serum IL-2 inhibitory factor was examined by IL-2-dependent mouse helper T cell line (HT-2). Significantly higher inhibitory activity was found in RA patients (p = 0.001) compared to OAD and normal control patients. Mycobacterium tuberculosis (MT) antigen was also examined from patients with RA and OAD, and 55.5% of SF from RA patients were positive for MT antigens and none was detected in OAD by a highly specific and sensitive double-antibody sandwich ELISA. However, no correlation between MT antigens, IL-2 levels and IL-2 inhibitory activities were found in patients with RA. Our results and other indicate that rheumatoid SF MNC, IL-2 inhibitor and MT antigen may play important roles in the pathogenesis of RA.

Adult↗

Drug-resistant tuberculosis in Cuba. Results of the three global projects.

SETTING: The spread of multidrug-resistant tuberculosis (MDR TB) in the world remains a major public health problem. Surveillance of anti-TB drug resistance is therefore an essential tool for monitoring the effectiveness of TB control program and, through policy development, for improving national and global TB control. OBJECTIVE: To determine the prevalence of anti-TB drug resistance in Cuba during the execution of the three global projects. DESIGN: Drug-resistance was determined using the proportion method in 1528 Mycobacterium tuberculosis strains to first line anti-TB drugs. RESULTS: Resistance in new cases was 8.3%, 4.6% and 5.0%; MDR was 0.7%, 0% and 0.3% in the first (1997), second (2000) and third (2004) global projects, respectively. In new cases, none showed resistance to the four drugs. There were among previously treated cases statistically significant decreases in the prevalence of resistance to at least one drug when comparing the results obtained in the three global projects. CONCLUSIONS: The contributed data through Cuba demonstrated that our country is relatively free of MDR strains, reflecting the good National Control Program and the possibility of TB elimination in Cuba.

Antitubercular Agents↗

Mycobacterial infection in natural killer T cell knockout mice.

To gain a better understanding of the pathological role of natural killer (NK) T cells in murine tuberculosis, NKT knockout (KO) mice (J(alpha)281(-/-)mice) were utilized. Eight-week-old NKT KO mice of BALB/c origin and wild-type (WT) mice were infected with Mycobacterium tuberculosis Kurono strain by the airborne route using an airborne infection apparatus, and their capacity to control mycobacterial growth, granuloma formation, and cytokine production were examined. The NKT KO mice developed granulomatous lesions in the lungs; there was no statistically significant difference in pulmonary granuloma size between NKT KO and WT mice (p<0.01). The average CFU values increased 3 weeks post-infection, but decreased 9 and 11 weeks post-infection, in the lungs of NKT KO mice. When stimulated with Kurono strain in vitro, splenic cells from NKT KO mice produced less IFN-gamma than did those from WT mice. Expression of mRNA for IL-2, IL-4, IL-6, IL-10 and IL-12 p40 was slightly lower in NKT KO mice compared with WT mice. Our data indicate that NKT cells play a detrimental role in late-phase mycobacterial infection, although Th1 cells are essential in early-phase mycobacterial infection.

Animals↗

[Secondary inactive pulmonary tuberculosis and non specific bronchial reactivity].

Bronchial reactivity to methacholine was examined in three groups of smokers (N = 93): subjects with secondary inactive pulmonary tuberculosis (TPI) 2 years after the beginning of treatment (N = 44); subjects with asymptomatic chronic bronchitis (N = 25) and healthy control (N = 24). Mean PC20FEV1 was 9.54 (SD 6.05), 11.12 (SD 5.42) and 13.74 (SD 4.7) respectively (tuberculosis vs control, p < 0.02). According to the arbitrary criteria for bronchial asthma, nonspecific hyperreactivity was present in 50% of subjects with TPI, in 37.5% of bronchitic patients and in 16% of control subjects. No difference was found with regard to PC20FEV1, the chemotherapeutic regimen (9 or 12 months of therapy), results of tuberculin test (normo and hyperreactive) and X-ray findings determined before the onset of treatment. Mahalanobis statistical analysis with respect to smoking index, basal ventilatory function tests and nonspecific bronchial reactivity grouped together healthy volunteers and subjects with a history of pulmonary tuberculosis apart from the group with asymptomatic chronic bronchitis.

Adult↗

Relation of leptin and tumor necrosis factor alpha to body weight changes in patients with pulmonary tuberculosis.

In this study we investigated whether leptin and TNFalpha levels change with improvement in body weight with antituberculotic therapy in active tuberculosis patients. 30 patients (8 females and 22 males) with active pulmonary tuberculosis formed the patient group, and 25 sex- and age-matched healthy subjects (8 females and 17 males) served as the control group. Body weight, body mass index (BMI) and serum leptin and plasma TNFalpha levels are measured before and in the sixth month of therapy in all patients. Before the initiation of therapy, BMI of the patients was significantly lower than BMI of the controls (20.2 +/- 1.6 vs. 25.2 +/- 2.7 kg/m(2), respectively; p < 0.05). After treatment, BMI of the patients increased significantly to 21.4 +/- 1.9 kg/m(2) (p < 0.05), but was still lower than that of the controls (p < 0.05). Pretreatment serum leptin (4.5 +/- 0.9 vs. 2.1 +/- 0.2 ng/ml, respectively; p < 0.05) and plasma TNFalpha (27.9 +/- 3.4 vs. 23.9 +/- 3.0 pg/ml, respectively; p < 0.05) levels of the patients were significantly higher than those of the controls. After treatment, serum leptin levels increased to 6.7 +/- 2.2 ng/ml, but this rise was not statistically significant (p > 0.05). Treatment did not result in any significant change in TNFalpha levels, either. Delta leptin was highly related to Delta BMI in patients with tuberculosis (r = 0.68, p = 0.02). In the pretreatment period, there was a significant correlation between leptin and TNFalpha levels in the whole patient group (r = 0.78, p < 0.001), and in female (r = 0.74, p < 0.001) and male patients separately (r = 0.74, p = 0.035). In conclusion, leptin and TNFalpha may be responsible for the weight loss in pulmonary tuberculosis patients, but their levels do not change with improvement in body weight with antituberculotic treatment.

Adult↗

A model of bovine tuberculosis control in domesticated cattle herds.

A typical strategy for disease control in domesticated animals involves regular field tests and quarantine of infected herds. This prevents disease spread beyond the herd, while slaughter of diseased animals removes the infection from within the herd. A model of bovine tuberculosis (Tb) control in cattle is examined, which includes 'test and slaughter' combined with herd isolation and vaccination. Herd status is represented by an integral equation expressing the duration of herd isolation. The current Tb situation in New Zealand is used as an example, and vaccination strategy discussed. Extrapolation of existing management strategies indicate that a vaccine of efficacy greater than 96% would be required, reaching 95% of target Tb levels within six years. These results suggest that a complementary strategy of vaccination and vector control may be more promising than vaccination alone.

Animals↗

[Trend of tuberculosis among young people observed from data of nationwide surveillance system].

In order to know the trend of TB incidence among people younger than 30 years of age, and to clarify the problem of TB control among them, the author used the surveillance data, the vital statistics, the annual reports of health center activities and others for the past 20 years. While the stagnation of the decline of TB incidence rate has been observed since early 1980s, the speed of decline among young people has been greater than that among people older than 30 years. However, at the same time it is worth attention that the incidence rate of the 20s is higher than that of those aged 30-39 years, and the slowing off more remarkable, during the last several years. It was shown that the recent increase of young immigrants from high prevalence countries is affecting the incidence of young age group (age 20-29) in Tokyo and the surrounding prefectures with higher proportion of these immigrant population. On the other hand, the high incidence in the young people observed in Osaka and the surrounding prefectures may be attributed to some other social risks. The BCG coverage for children aged 0-4 years has been increasing and reached to 90% in 1991. The tuberculin test results of children in an area seems to reflect the technical level of the testing and the age of children to be tested, rather than the TB prevalence of the area. The frequency of the young people under chemoprophylaxis is widely variable among prefectures. There is poor correlation between this frequency of chemoprophylaxis of prefectures and the incidence rate of sputum positive TB, which may be caused by disparity in recognition of the necessity of the chemoprophylaxis and the lack of efforts for the quality control of the services, such as tuberculin testing.

Adolescent↗

The secretory immunoglobulin A response to Mycobacterium tuberculosis in a childhood population.

We report on the measurement of saliva anti-Purified Protein Derivative sIgA and 38kDa antibodies from 127 children, of whom 31 were strong tuberculosis suspects and 96 were healthy contact children. The results concerning the percentage of children with antibody reactivity to PPD and 38kDa antigens showed that, of these 2 antigens, 38kDa induced higher reactivity in patients positive and negative for the Tuberculin Skin Test (28% and 16.6%, respectively) in comparison to controls positive and negative for the TST (11.7% and 7.1%, respectively). There was a statistically significant difference between patients positive and controls negative for the TST. In relation to the Purified Protein Derivative antigen, while 14.2% of patients positive for the TST showed antibody reactivity to the PPD antigen, no patients negative for the TST had reactivity to this antigen. The findings suggest that these two antigens seem be associated with a different development of the mucosal defence mechanisms mediated by sIgA against Mycobacterium tuberculosis.

Adolescent↗

The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model.

OBJECTIVE: To explore the potential impact of enhanced tuberculosis (TB) diagnostic techniques as a TB control strategy in an adult population with high HIV prevalence. DESIGN: A compartmental difference-equation model of TB/HIV was developed using parameter estimates from the literature. METHODS: The impact of five TB control interventions (rapid molecular testing, mycobacterial culture, community-wide and HIV-targeted active case finding, and highly active antiretroviral therapy) on TB incidence, prevalence, and mortality was modeled in a steady-state population with an HIV prevalence of 17% and annual TB incidence of 409 per 100 000. Sensitivity analyses assessed the influence of each model parameter on the interventions' mortality impact. RESULTS: Enhanced diagnostic techniques (rapid molecular testing or culture) are each projected to reduce TB prevalence and mortality by 20% or more, an impact similar to that of active case-finding in 33% of the general community and greater than the effect achievable by case-finding or antiretroviral treatment efforts in HIV-positive patients alone. The projected impact of enhanced diagnostics on TB incidence (< 10% reduction) is smaller. The impact of TB diagnostics is sensitive to the quality of existing diagnostic standards and the level of access to diagnostic services, but is robust across a wide range of population parameters including HIV and TB incidence. CONCLUSIONS: Enhanced TB diagnostic techniques may have substantial impact on TB morbidity and mortality in HIV-endemic regions. As TB rates continue to increase in these areas, enhanced diagnostic techniques merit further consideration as TB control strategies.

AIDS-Related Opportunistic Infections↗

Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence area.

Deciphering the structure of pathogen populations is instrumental for the understanding of the epidemiology and history of infectious diseases and for their control. Although Mycobacterium tuberculosis is the most widespread infectious agent in humans, its actual population structure has remained hypothetical until now because: (i) its structural genes are poorly polymorphic; (ii) adequate samples and appropriate statistics for population genetic analysis have not been considered. To investigate this structure, we analysed the statistical associations (linkage disequilibrium) between 12 independent M. tuberculosis minisatellite-like loci by high-throughput genotyping within a model population of 209 isolates representative of the genetic diversity in an area with a very high incidence of tuberculosis. These loci contain variable number tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed repetitive units (MIRUs). Highly significant linkage disequilibrium was detected among the MIRU-VNTR loci in this model. This linkage disequilibrium was also evident when the MIRU-VNTR types were compared with the IS6110 restriction fragment length polymorphism types. These results support a predominant clonal evolution of M. tuberculosis.

Bacterial Typing Techniques↗