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PubMed2006

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↗
PubMed2003

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↗
PubMed2005

Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States.

On May 2, 2005, a new in vitro test, QuantiFERON-TB Gold (QFT-G, Cellestis Limited, Carnegie, Victoria, Australia), received final approval from the U.S. Food and Drug Administration as an aid for diagnosing Mycobacterium tuberculosis infection. This test detects the release of interferon-gamma (IFN-g) in fresh heparinized whole blood from sensitized persons when it is incubated with mixtures of synthetic peptides representing two proteins present in M. tuberculosis: early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). These antigens impart greater specificity than is possible with tests using purified protein derivative as the tuberculosis (TB) antigen. In direct comparisons, the sensitivity of QFT-G was statistically similar to that of the tuberculin skin test (TST) for detecting infection in persons with untreated culture-confirmed tuberculosis (TB). The performance of QFT-G in certain populations targeted by TB control programs in the United States for finding latent TB infection is under study. Its ability to predict who eventually will have TB disease has not been determined, and years of observational study of substantial populations would be needed to acquire this information. In July 2005, CDC convened a meeting of consultants and researchers with expertise in the field to review scientific evidence and clinical experience with QFT-G. On the basis of this review and discussion, CDC recommends that QFT-G may be used in all circumstances in which the TST is currently used, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (e.g., those for health-care workers). This report provides specific cautions for interpreting negative QFT-G results in persons from selected populations. This report is aimed at public health officials, health-care providers, and laboratory workers with responsibility for TB control activities in the United States.

Antigens, Bacterial↗
PubMed1990

[Tissue polypeptide antigen in serum and tissue in patients with lung cancer].

To evaluate the significance of TPA (tissue polypeptide antigen) as a tumor marker for lung cancer, the present studies were designed to measure serum TPA levels as well as TPA contents in tumor tissues in patients with lung cancer. Average serum TPA levels (203.5 +/- 180.5 U/l, mean +/- SD) in 76 patients with lung cancer (30 squamous cell carcinoma, 38 adenocarcinoma, 8 small cell carcinoma) were significantly higher than those in pneumonia (83.3 +/- 42.7 U/l, n = 13), pulmonary tuberculosis (87.6 +/- 36.3 U/l, n = 16), and normal controls (46.8 +/- 23.7 U/l, n = 28). There was no significant difference in TPA levels according to the histological type of lung cancer. Comparing respective stage cases, statistically significant differences were observed in serum TPA levels between normal controls and stage 1, stage 1 and stage 3, and in stage 3 and stage 4, suggesting a gradual increase in TPA levels accompanying the progress of the lung cancer. In patients with 12 squamous cell carcinoma and 9 adenocarcinoma, the TPA levels in carcinoma tissues and non-tumor invaded lung tissues were 115.2 +/- 187.7 and 148.9 +/- 223.3 U/mg protein, indicating no significant difference in carcinoma and normal tissues. There was definite correlation between serum TPA levels and TPA contents in carcinoma tissues. No significant relationship, however, was observed between serum TPA levels and TPA contents in tissue not invaded by tumor. These results suggest that serum TPA levels reflect the tumor burden in patients with lung cancer. In conclusion, the determination of TPA in blood is useful for the diagnosis of lung cancer.

Adenocarcinoma↗
PubMed1989

Is natural infection with M. tuberculosis protective against cancer?

In order to investigate the effect of natural infection with M. tuberculosis on cancer incidence, a case-control study was undertaken on 108 recently diagnosed cancer cases (all sites) and 317 controls. After removal of cancer cases or controls considered immunoincompetent (25% and 17% respectively), the remaining subjects were tested by intradermal injection of tuberculin (5 I.U.). Results were compared separately for each sex. It was observed that the proportion of tuberculin-negative subjects was higher in cancer patients than in controls within each sex (males 31.3% vs 20.1%, females: 59.2% vs 37.3%) the difference in females being statistically significant (p less than 0.02). Odds ratio for negative tuberculin test was 1.80 and 2.44 for males and females respectively. The results are discussed on the basis of cell-mediated immunity produced by infection with M. tuberculosis and its relations with tumor growth.

Cohort Studies↗
PubMed1999

The effect of immunodeficiency on cutaneous delayed-type hypersensitivity testing in HIV-infected women without anergy: implications for tuberculin testing. HER Study Group. HIV Epidemiology Research.

SETTING: A collaborative study in four urban medical centers in the United States. OBJECTIVE: To determine the effect of human immunodeficiency virus (HIV) infection and immunodeficiency on delayed type hypersensitivity (DTH) responses and the implications for interpretation of tuberculin reactions in non-anergic women with or at risk for HIV infection. DESIGN: Demographic and behavioral information, HIV antibody testing, CD4+ lymphocyte counts, and cutaneous responses to DTH testing with mumps, Candida, tetanus toxoid, and tuberculin (purified protein derivative-PPD) antigens were obtained in 1184 women. RESULTS: Reactions to one or more of the four antigens occurred in 436 HIV-seropositive and 356 high-risk seronegative women. Among non-anergic women, HIV-seropositives were less likely (P < or = 0.05) to react to mumps (62% vs 81%), tetanus (72% vs 84%), and PPD (13% vs 19%). Induration in HIV-seropositive reactors was associated with CD4+ cell level for mumps (P = 0.004) and tetanus (P < 0.001), but not for Candida or PPD. HIV-seropositive reactors with CD4+ cell counts >500/mm3 did not have significantly smaller reactions than HIV-seronegatives for any antigen tested. PPD sizes were similar among HIV-seropositive reactors with CD4+ cell counts >500/mm3 (12.4 +/- 7.4 mm) and HIV-seronegative reactors (12.0 +/- 8.3 mm); induration > or =10 mm was seen in 16/173 (9.2%) seropositive women with CD4+ cell counts >500/mm3 and 41/356 (11.5%) seronegative women, respectively (P = 0.5). CONCLUSION: Among HIV-infected women able to react to a DTH antigen, induration in response to that antigen was relatively intact at CD4+ counts >500/mm3. This suggests that degree of immunodeficiency should be considered when interpreting PPD reactions in HIV-infected persons.

Adolescent↗
PubMed1997

A randomised placebo-controlled trial of the efficacy of beta-sitosterol and its glucoside as adjuvants in the treatment of pulmonary tuberculosis.

OBJECTIVE: To evaluate the adjuvant effect of beta-sitosterol and its glucoside in the treatment of culture proven pulmonary tuberculosis (PTB). DESIGN: A blinded randomised placebo-controlled trial in culture proven drug sensitive PTB. Patients were hospitalised for the duration of treatment and evaluated at monthly intervals with regard to sputum culture positivity, chest radiography, weight gain, Mantoux test response, routine haematology and liver functions. STATISTICAL EVALUATION: General linear models for repeated measures (SAS GLM package) compared the interaction effects, group effects and time effects of findings in 19 patients receiving sitosterols with those in 18 patients receiving a placebo (talcum powder). Absolute values and change from baseline values were evaluated, although only the latter are reported. RESULTS: Weight gain was significantly greater in the sitosterol group (mean weight gain 8.9 kg) than the placebo group (mean gain 6.1 kg) (P = 0.0023 group effects; P = 0.0001 for time effects). Speed of achieving culture negativity, radiological improvement and induration on Mantoux testing was similar in the two groups. Change in lymphocyte counts from baseline was significantly higher in the sitosterol group (P = 0.0001 and P = 0.0001 for group and time effects) as was the increase in eosinophil counts (P = 0.0001 and P = 0.0137 for group and time effects). CONCLUSION: The study has shown significantly improved weight gain and higher lymphocyte and eosinophil counts in PTB patients receiving sitosterols in addition to an efficacious antituberculosis regimen. Sitosterols and their possible mode of action should now be evaluated in larger numbers of tuberculosis patients and in diseases with a similar immunopathogenesis.

Adjuvants, Immunologic↗
PubMed1989

Detection of mycobacterial antigens in cerebrospinal fluid by enzyme-linked immunosorbent assay utilizing anti-mycobacterial saline extract antibodies.

Using anti-mycobacterial saline extract antibodies, Mycobacterium tuberculosis antigens can be detected in cerebrospinal fluid by a highly specific and sensitive double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). The ELISA was dose-dependent and capable of detecting as little as 6.0 ng of antigens. Specificity was demonstrated by negative results (0.063 +/- 0.008) with other bacterial and cryptococcal antigens (n = 9), and maximum cross-reactivity with other mycobacteria was less than 2.0%. Absorbance for six patients with confirmed tuberculous meningitis gave results ranging from 0.168 to 0.898 with a mean value of 0.393 +/- 0.248. For 172 nonmeningitis and nontuberculosis control patients and 6 treated tuberculous meningitis patients, optical densities were 0.064 +/- 0.001 and 0.057 +/- 0.007, respectively. Significant statistical difference (p less than 0.001) was found between the tuberculous meningitis and control groups.

Animals↗
PubMed2002

Tuberculosis and vitamin D deficiency.

OBJECTIVES: a) To find out the normal level of 25 hydroxy vitamin D in healthy individuals b) To look for evidence of vitamin D deficiency in patients with active tuberculosis. METHODS: There were 35 cases of pulmonary and extra-pulmonary tuberculosis and 16 controls, whose clinical characteristics, dietary intake of vitamin D and biochemical characteristics including serum vitamin D levels were compared. EXCLUSION CRITERIA: malabsorption, liver or renal disorders, intake of drugs, which can reduce vitamin D levels, HIV infection, diabetes, immunosuppressive treatment, and severe protein energy malnutrition. RESULTS: There was a statistically significant difference (p < 0.005) in mean vitamin D levels between controls (19.5 ng/ml) and study subjects (10.7 ng/ml). Sixteen patients out of 35 had values well below the lower limit of normal (9 ng/ml). No one in the control group had vitamin D level less than 9 ng/ml. However the mean vitamin D level in the control group was less than the mean value quoted in the literature from the West. Sunlight exposure was adequate in those with deficiency but there was reduced dietary intake of vitamin D. CONCLUSIONS: Serum 25 hydroxy vitamin D levels less than 9 ng/ml indicates deficiency. Vitamin D deficiency exists in patients with tuberculosis and it is possibly a cause rather than effect of the disease; deficiency is due to decreased dietary intake. Vitamin D deficiency can occur without any symptoms. If symptoms are present, it indicates severe deficiency. Serum calcium and phosphorus values do not often predict the existence of deficiency.

Adolescent↗
PubMed2006

[Preliminary results of testing The WHO Guidelines for Tuberculosis Control in the Republic of Chuvashia].

The authors describe the first results of introduction of the WHO recommendations for tuberculosis control in the Republic of Chuvashia. The total number of studies performed in the general therapeutic network and in tuberculosis facilities has increased by 1.3 and 1.5 times, respectively. The microscopic diagnosis of Mycobacterium tuberculosis in the sputum has improved, increasing the detection rate of tuberculosis from the smear, particularly in the general network, from 2.2% to 24.2%, but at the same time leading to higher morbidity in the republic. There has been improvement of the efficiency of treatment in patients by the generally accepted statistical indicators: abacillation by 19.7%, decay cavity closure by 11.3%, and being taken off the book of bacterial isolates by 15%. On completion of intensive-phase treatment of patients with pulmonary tuberculosis, negative sputum tests have been 84.7% in the tuberculosis facilities and 91.7% in the Federal Services penitentiaries. The interaction has become better between the penitentiary system and the tuberculosis-controlling service.

Catchment Area, Health↗
PubMed2004

Proinflammatory cytokine profile in active kidney tuberculosis patients.

INTRODUCTION: Mycobacterium tuberculosis is a facultative intracellular pathogen that developes specific T cell response expressed by the production of IL-12, IFN-gamma, and TNF-alpha. The response has been quite well investigated in the experimental models, however, there is little information about certain cytokine levels in patients with extrapulmonary tuberculosis. The shortage of data pertains also to its most common form-kidney tuberculosis, especially when bacilli dissemination into the blood circulation has occurred. OBJECTIVES: The aim of our study was to examine simultaneously the frequency of Mycobacterium tuberculosis presence in the blood circulation and the serum cytokine concentration during kidney tuberculosis to approach their relationship in the clinical infection process. It is considered that cytokine levels do not correlate with localisation of tuberculosis (pulmonary vs. extrapulmonary), however, there is little information about the cytokine levels in patients with kidney tuberculosis. MATERIALS AND METHODS: 30 patients attending the urology clinic with suspicion of kidney tuberculosis were evaluated. Serum concentrations of selected cytokines in patients with urine, urine and blood Mycobacterium tuberculosis presence were quantified by ELISA and compared to PCR negative patient and group of healthy people. RESULTS: Our study demonstrates the increase of TNF-alpha and IL-12 level in comparison to control group. TNF-alpha concentration was about 2-fold higher in the positive patients than it was in control group; IL-12 concentration was about 4-fold higher and the differences between IL-12 levels were statistically important (p < 0.05). However, no significant differences were found in IFN-gamma level among all groups. Using Spearman correlation rank test, a significant correlation was found between TNF-alpha and IL-12 in the positive patient group. The correlation factor was more significant for the group of patients with Mycobacterium tuberculosis present in blood and urine than it was in urine positive PCR group (r = -0.66 vs. r = -0.51).

Adult↗
PubMed2003

[A study of the psychological and social factors in patients with pulmonary tuberculosis].

OBJECTIVE: To investigate the mental health and social support in patients with tuberculosis. METHODS: Questionnaires were performed in 132 patients with tuberculosis and 71 healthy volunteers using Symptom Checklist 90 (SCL-90) and Social Support Rating Scale (SSRS). Statistical analyses were processed using Student's t test and ANOVA test. RESULTS: Somatization, obsessive-compulsiveness, anxiety, phobic anxiety and paranoid ideation, psychotism and the mean of positive factors of SCL-90 of the tuberculosis group (1.77 +/- 0.51, 1.63 +/- 0.50, 1.53 +/- 0.51, 1.33 +/- 0.41, 1.40 +/- 0.45, 1.41 +/- 0.40 and 36.07 +/- 20.84, respectively) were significantly higher than those of the control group (1.30 +/- 0.49, 1.43 +/- 0.49, 1.38 +/- 0.65, 1.24 +/- 0.48, 1.49 +/- 0.69, 1.30 +/- 0.44 and 24.92 +/- 18.22, respectively) (all P < 0.01). The result of symptom self-check differed among patients with different educational levels. The SSRS results of subjective and objective supports and total score of social supports of the tuberculosis group were 6.90 +/- 2.81, 19.25 +/- 5.62 and 32.96 +/- 7.86, respectively, much lower than those of the control group (7.92 +/- 2.57, 21.54 +/- 5.82 and 36.51 +/- 9.01, respectively) (all P < 0.01). Subjective support of patients with smear positive tuberculosis was much lower than that of patients with smear negative disease (18.15 +/- 5.72 vs. 20.75 +/- 5.78, P < 0.05); Subjective support, objective support and total score of social support of the unmarried patients (17.19 +/- 4.20, 6.17 +/- 2.18, 30.35 +/- 5.96, respectively) were lower than those of the married (20.72 +/- 5.96, 7.66 +/- 3.03, 35.19 +/- 8.74, respectively) (all P < 0.01). The results of SCL-90 and SSRS had no statistical relationship. CONCLUSION: Our results suggest that the disordered mental conditions and lower social support in patients with tuberculosis need psychosocial interventions in addition to medical care.

Adolescent↗
PubMedDate not supplied

[Hypersensitivity pneumonitis in Mexico City].

OBJECTIVE: To investigate the association between the urban area of origin of patients and the prevalence of hypersensitivity pneumonitis (HP), induced by avian antigens. MATERIAL AND METHODS: A case-control study was conducted in 1999 at the National Institute of Respiratory Diseases (NIRD). Cases were 109 consecutive HP patients and controls were 184 patients: 39 with idiopathic pulmonary fibrosis (IPF), 63 with pulmonary tuberculosis (PTB), and 82 with asthma. Mexico City and surrounding counties (SC) were divided into 5 geographical areas: 1) Downtown; 2) North-East (NE); 3) South-East (SE); 4) North-West (NW) and 5) South-West (SW). Statistical analysis consisted of calculation of disease prevalence by urban area; associations were assessed with odds ratios and 95% confidence intervals. Multivariate analysis with multiple logistic regression was performed to adjust for age, gender and socioeconomic level. RESULTS: Eighty HP cases were located in the NE southernmost and SE northernmost areas of Mexico City (48 and 32, respectively) (OR = 3.86; 95% CI 2.17-6.96). Thirty-six controls with asthma came from the SW area, (where NIRD is located) (p < 0.05), and four from SC. Controls with PTB and IPF were scattered throughout the study area. CONCLUSIONS: The NE southernmost and SE northernmost areas were associated with HP. The cause of HP may not be geographical; a garbage dump used to be located in this area, suggesting that exposure to organic particles might contribute to the development of HP in susceptible individuals.

Adult↗
PubMedDate not supplied

[The late results of intensive chemotherapy (9 months) in severe forms of tuberculosis in children].

The short-course chemotherapy (9 months) in the severe forms of tuberculosis in children is a very modern item. It was very few approached on an international level and relatively short time ago in our country. There were applied the following therapeutical regimens: 3 HRZ2 6 HR2 (in the experimental group) and 3 HR/3 HR2/6 H2 (in the control group). In the granulias and the caseous forms the late results, at 5 years after treatment end, were very good in 100% of cases in both groups. In meningitis clinical very good results (without sequellae) presented a proportion of 70.1% in the experimental group and of 68.2% in the control group (difference statistically non significant). The main advantage of the intensive short course regimens (9 months) comparatively with the "classical" ones (of at least 12 months) consists in reaching finally the same good results but in at least 3 months shorter time interval.

Adolescent↗
PubMed1983

[Measuring the effectiveness of different variants of tuberculosis control using simulation models].

Simulation and predictive models of tb epidemiological trends in the Czech Socialist Republic (CSR) for the 1949-2000 period were devised taking into account several variants of tb control measures. AZUMA'S simulation model from Japan was used as the basis for the mathematical processing and adapted in different parts to satisfy the conditions prevailing in the CSR. The initial conditions and parameters to go into the equations of the model were determined or estimated from statistical data for the whole of CSR or from the results of some of the more detailed partial studies. An Olivetti P 6060 minicomputer was used for calculations. Statistical data were found in satisfactory agreement with trends estimated from model simulations. The simulation models revealed that the epidemiological trends were most influenced by the treatment, less by the BCG vaccination and the least by the active case finding. As suggested by the predictive simulations, discontinuation of the programme of tb control would result in a major deterioration of the epidemiological situation.

BCG Vaccine↗
PubMed1993

Evaluation of the efficacy of health education on the compliance with antituberculosis chemoprophylaxis in school children. A randomized clinical trial.

Chemoprophylaxis against tuberculosis with isoniazid for 1 year is very useful, but patient compliance is very low. A controlled clinical trial was performed to evaluate the efficacy of three alternative health education strategies and to observe which of them improves compliance with antituberculosis chemoprophylaxis in healthy tuberculin-reactor children. Although all three strategies achieved positive, statistically significant results as compared with the control group, that performed by nursing personnel at the patient's home is the most effective, followed by that performed by the same health professionals by telephone. The least effective strategy by far was that performed by the physician in his surgery.

Child↗
PubMed1997

Costs and benefits of improving tuberculosis control: the case of Thailand.

The study evaluates the economic costs and benefits of improving tuberculosis control interventions in Thailand. Provider costs are determined on the basis of marginal treatment costs for varying case numbers and estimates of the cost of required infrastructure changes. Indirect costs are calculated as income lost due to morbidity and premature mortality. An epidemiological model is used to calculate case numbers and mortality under current control conditions and a scenario of improved control. An improved control strategy initially leads to a higher number of detected cases. For longer projection periods, the epidemiological impact of curing a higher proportion of infectious sources results in lower case numbers than those expected without programme improvement. Model simulations show a reduction of total annual case numbers through improved control measures by an average 45% after a simulation period of 20 years. The corresponding societal savings in form of reduced indirect costs from the disease are U.S.$2.4 billion. Reductions in direct provider costs can be expected as a result of decreased numbers of detected cases for longer evaluation periods, as well as a lower proportion of multi-drug-resistant cases. The mean value of predicted savings is U.S.$8.3 million. Since this value is likely to be higher than the required investment in improved infrastructure, net savings can be expected. The result of an uncertainty analysis shows a wide range of potential additional costs or net savings with respect to direct provider costs. Indirect cost calculations show net savings for all parameter values.

Communicable Disease Control↗