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PubMed2004

[Randomized control study on domestic fixed-dose combinations in the initial treatment of smears positive tuberculosis].

OBJECTIVE: To explore the feasibility of domestic fixed-dose combinations as antituberculosis therapy applied in the National Tuberculosis Program. METHODS: A randomized control trial was conducted and 422 smear-positive pulmonary tuberculosis patients were randomly distributed into 2 groups. The trial group was treated daily with rifampicin, isoniazid and pyrazinamide tablets (including 120 mg rifampicin, 80 mg isoniazid and 250 mg pyrazinamide) in the first 2 months and rifampicin and isoniazid tables (including 300 mg rifampicin, 150 mg isoniazid) in the subsequent 4 months. The control group was treated by full 6-month standard regimens (2HRZE/4H3R3). RESULTS: The demographic data and the disease status were similar between the 2 groups before treatment. The rate of conversion from positive to negative cases in the trial group after therapy was 91.6% at 2 months, 97.2% at 3 months, and 97.7% at 6 months, while that of the control group was 87.3%, 97.5%, and 98.0% respectively. The difference in the conversion rates between the two groups was not statistically significant (chi2 = 2. 05, chi2 = 0.03, chi2 = 0.04, P > 0.05). The incidence of skin rash as an adverse effect was less common in the trial group as compared to the control group (Fisher's exact P = 0.024 33) . CONCLUSIONS: Domestic fixed-dose combinations as supplementary anti-tuberculous therapy could be used in the National Tuberculosis Program, but further study is needed for widespread application.

Adolescent↗
PubMed2004

Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient.

Renal transplantation (RT) recipients are at a high risk of developing tuberculosis (TB) following transplantation. Effectiveness of isoniazid (INH) in preventing TB is well documented in immunocompetent as well as immunocompromised persons. There is paucity of data on role of INH prophylaxis in RT recipients. Thus, a prospective randomised trial of INH in RT recipients was carried out to determine the efficacy of daily INH monotherapy in the prevention of TB in these patients. Patients of end stage renal disease (ESRD) taken for RT formed the subjects of study. Patients with active TB and active hepatitis at the time of RT were excluded from the study. Patients were randomised to receive INH 300 mg with pyridoxine 20 mg daily from the day of RT. The duration of the treatment was planned for 1 year or till the development of TB, which ever was earlier. Between October 1998 and September 2000, 114 RT were done at our hospital. Of these, 24 (21%) patients had active TB at the time of RT and thus were excluded. Patients included were randomised with 1:2 ratio of treatment and control group. Of the 90 patients thus enrolled, 30 were randomised in treatment group and 60 in control group. Of the included patients five patients had very early graft loss (three in treatment and two in control group) within days and thus excluded from the analysis. Three of the 27 (11.1%) patients in treatment group and 15 (25.8%) in control group developed TB (P = 0.10). The risk ratio of (RR) of INH versus control group of TB was 0.36 (95% CI, 0.10-1.32) but the difference was not statistically significant (P = 0.12). Only one patient developed INH induced hepatitis. In conclusion, with INH prophylaxis, there was a trend towards protection from TB, though it was not statistically significant. Further, all patients tolerated INH and hepatotoxicity was not a major problem in this group of patients.

Antitubercular Agents↗
PubMed2006

[Risk factors for the development of pulmonary tuberculosis among type 2 diabetes mellitus patients].

OBJECTIVE: To explore risk factors for pulmonary tuberculosis among type 2 diabetes mellitus patients (DM-PTB). METHODS: A hospital-based case-control study was conducted at three hospitals in Tianjin during October 2001 to October 2002. 87 newly-diagnosed PTB patients with type 2 DM were recruited as cases, and 129 type 2 DM patients were chosen as controls. Information on risk factors was collected through face-to-face interview. Univariate unconditional logistic regression model and multivariate logistic regression modified by the factor analysis were conducted to explore the risk factors for DM-PTB and final main effect functions were built by age and sex. RESULTS: 31 variables were found to be associated with DM-PTB in the univariate analysis. The modified multivariate logistic regression analysis found that bad contact factor (OR = 1.778, 95% CI: 1.248 - 2.534), severe state of DM (OR = 1.749, 95% CI: 1.221 - 2.506), bad habits factor (OR = 1.614, 95% CI: 1.136 - 2.294) and low intake of salt (OR = 1.586, 95% CI: 1.119 - 2.248) were generally associated with increased risk of DM-PTB in the final model; while factors as good habits (OR = 0.333, 95% CI: 0.218 - 0.508), high socioeconomic level (OR = 0.508, 95% CI: 0.346 - 0.745), hypertension (OR = 0.517, 95% CI: 0.350 - 0.764), good housing condition (OR = 0.599, 95% CI: 0.413 - 0.868) and beneficial change of diet after DM (OR = 0.630, 95% CI: 0.447 - 0.889) were shown to be reversely associated with DM-PTB. CONCLUSION: Different genders and different ages have different risk factors or protective factors. Thus, to reduce the progressively increased incidence of PTB among DM patients, preventive strategies and measures should be focused on the most vital predisposing factors in corresponding risk populations.

Age Factors↗
PubMed2002

Transmission dynamics of tuberculosis in Tarrant county, Texas.

To understand the transmission dynamics of tuberculosis in Tarrant County, Texas, we performed a population-based study of 159 patients with culture-proven tuberculosis, combining restriction fragment length polymorphism (RFLP) analysis of Mycobacterium tuberculosis isolates with prospective interviewing to identify epidemiologic links between patients. Patients whose isolates had identical or closely related RFLP patterns were considered a cluster. Seventy-six (48%) of 159 patients were in 19 clusters, suggesting that recent transmission accounted for 36% of tuberculosis morbidity. Unconditional logistic regression showed that birth in the United States, continuous residence in Tarrant County, a history of homelessness, and a history of visiting or working in bars were independent predictors of clustering. Four homeless shelters and five bars were associated with specific clusters, suggesting that they were sites of tuberculosis transmission. Patients in some clusters recognized more photographs of patients in their cluster than did patients outside their cluster. We conclude that (1) homeless shelters and bars are important sites of tuberculosis transmission in Tarrant County, and (2) the use of photograph recognition of patients with tuberculosis, in combination with RFLP analysis, has the potential to enhance tuberculosis control by facilitating identification of epidemiologic links between patients.

Adult↗
PubMedDate not supplied

Vaccines against mycobacteria and other intracellular multiplying bacteria.

As the prototype of a vaccine against mycobacterial infection, the BCG (bacille bilié Calmette et Guérin) has been used against tuberculosis for more than 60 years. It is the only live attenuated vaccine used on humans in more than 182 countries or territories in the world, and very few changes have been made in its fabrication and distribution, except for the production of lyophilized seed-lots. However, its history is marked with controversies concerning its innocuity and efficacy. While BCG safety is no longer a matter of debate, the question of its effectiveness is still pertinent, and results in several controlled trials have shown great variability (from 0 to 80%). The studies of different variables involved in such results have shown statistical bias, and numerous factors are involved in the highly complex interrelationships between the host, the pathogen and environmental factors. World-wide research is now being conducted under the auspices of the World Health Organisation, in order to gain further knowledge of the immunology of tuberculosis and leprosy. Such results are aimed at understanding variations in BCG efficacy and producing strategies for developing new vaccines and alternative methods for prophylaxis and diagnosis. Concerning human infections due to other facultative intracellular multiplying bacteria, there are relatively few vaccines which are able to give long-lasting and efficient protection. Some controversy remains as to the live attenuated mutant GalE S. typhi Ty21a, and there is hope for the new insoluble phenol extract from Brucella abortis, strain B19. Further research is necessary on the others, for instance, Listeria monocytogenes, Chlamydia trachomatis and Legionella sp.

Bacterial Infections↗
PubMed2001

[A nutritional investigation of homeless patients with tuberculosis].

A retrospective case-control study was performed with TB patients who were admitted to our hospital over the two years from Jan. 1997 to Dec. 1998 and healthy men who underwent a health screening in April 2000 in the same hospital. Thirty-two non-homeless TB patients (the first control group) and 32 healthy men (the second control group) were matched with 32 homeless TB patients according to age. All 3 groups were male. Total protein, albumin, cholesterol, cholinesterase, hemoglobin level and lymphocyte count on admission were significantly lower in the homeless patients than in the non-homeless patients and healthy men. Albumin, cholesterol, cholinesterase, hemoglobin level, white blood cell count and lymphocyte count on admission were significantly lower in non-homeless patients than healthy men. Height, weight and body mass index were significantly lower in the homeless patients than in the healthy men. However, there were no significant differences in these body characteristics between the homeless and non-homeless patients. Twenty-five percent of homeless patients died during hospitalization, compared with 6.3 percent of non-homeless patients. Lymphocyte counts among homeless patients who died during hospitalization were significantly lower than among those who survived during hospitalization. Total protein, albumin, cholesterol, cholinesterase, hemoglobin level and weight were lower in patients who died than in those who survived, although the differences were statistically not significant.

Adult↗
PubMed1992

Leukemia, lymphoma, and multiple myeloma following selected medical conditions.

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.

Aged↗
PubMed1996

Storing sparse and repeated data in multivariate Markovian models of tuberculosis spread.

Through the use of appropriate sparse storage techniques, we were able to reduce memory usage in a multivariate Markovian model for the spread of tuberculosis in the United States through the year 2010. A straightforward software implementation of the model would have required approximately 2.5 x 10(9) bytes of storage for the population of each year being modeled and approximately 1.3 x 10(14) bytes of storage for each year-to-year set of transition probabilities. We were able to reduce memory usage in the model by 96% for cross-sectional population data and over 99.9% for transition probability data. Data structure initialization time for population data was increased by a factor of 16.48 and lookup time for population data was increased by a factor of 11.3 over times required for an array implementation. For transition data the initialization and lookup times were increased by negligible factors. This work was done under contract from the Centers for Disease Control and the Association of Teachers of Preventive Medicine.

Centers for Disease Control and Prevention, U.S.↗
PubMed2002

Shifts of T4/T8 T lymphocytes from BAL fluid and peripheral blood by clinical grade in patients with pulmonary tuberculosis.

OBJECTIVES: We investigated the shifts of T4/T8 lymphocytes from BAL fluid (BALF) and peripheral blood by the clinical grade of pulmonary tuberculosis (TB), which is determined by factors such as extent of pulmonary involvement, fever, and loss of body weight. MATERIALS AND METHODS: In order to explore these questions, BALF was collected from 45 patients presenting with active pulmonary TB and 14 healthy control subjects. The percentages for T-lymphocyte subpopulations, including CD4(+), CD8(+), and CD3(+) T cells, were measured using two-color flow cytometry. RESULTS: A higher percentage of CD3(+)CD4(+) T lymphocytes, with a relatively lower percentage of CD3(+)CD8(+) T lymphocytes, was revealed for the patients with a higher grade of pulmonary TB, compared to patients with a lower grade of pulmonary TB, resulting in an increased BALF C4(+)/CD8(+) ratio. By contrast, a higher percentage of CD3(+)CD8(+) T lymphocytes with a relatively low percentage of CD3(+)CD4(+) T lymphocytes was demonstrated for these patients with a higher grade of pulmonary TB, resulting in a decreased peripheral blood CD4(+)/CD8(+) ratio. CONCLUSIONS: Our findings suggest that compartmentalization of the CD4(+) T lymphocytes in the infected lungs may occur for patients with higher grades of pulmonary TB.

Adult↗
PubMed2006

Selection of novel TB vaccine candidates and their evaluation as DNA vaccines against aerosol challenge.

Putative TB vaccine candidates were selected from lists of genes induced in response to in vivo-like stimuli, such as low oxygen and carbon starvation or growth in macrophages, and tested as plasmid DNA vaccines for their ability to protect against Mycobacterium tuberculosis challenge in a guinea pig aerosol infection model. This vaccination method was chosen as it induces the Th1 cell-mediated immune response required against intracellular pathogens such as M. tuberculosis. Protection was assessed in the guinea pig model in terms of mycobacteria present in the lungs at 30 days post-challenge. Protection achieved by the novel candidates was compared to BCG (positive control) and saline (negative control). Four vaccines encoding for proteins such as PE and PPE proteins, a zinc metalloprotease and an acyltransferase, gave a level of protection that was statistically better than saline in the lungs. These findings have enabled us to focus on a sub-set of vaccine candidates for further evaluation using additional vaccination strategies.

Aerosols↗
PubMed2001

[Strategy of tuberculosis control and achievement in Okinawa].

After fierce battles in World War II, Okinawa was occupied by military of U.S.A. and consequently was administrated by USCAR (United States Civil Administration of Ryukyus). During 27 years from April 1945 to May 1972, reversion to Japan, the public Health Activities including T.B. control were performed by Ryukyus Government indirectly controlled by USCAR. The first issue of T.B. statistics was made in 1950. It revealed remarkable reduction of T.B. death rate, a quarter of that before the war. The main reasons of the reduction were considered due to the over-death in battles. But epidemic of T.B. had increased rapidly, especially since the Korean War occurred in 1950. Constructions of the military base were booming, and T.B. infection was spread among laborers, employees, and also their families. Then, Ryukyus Government enacted a temporary law of T.B. prevention and control in 1954. Home-care treatment of T.B. patient was started with registration and management in newly constructed Public Health Centers. Because of shortage of government budget, man-power including doctor and poor institutes, a system of short-termed admission treatment (6 months) and home cared chemotherapy were started. Public Health Nurses (PHN) took care the patient at home, and medical fee of T.B. treatment was free in charge to patients. So activities of PHN were very important. In 1962, Dr. Shoukou Imamura, from JATA, came to study the system of home care treatment. And 7,000 cases under supervision of Public Health Center were investigated. He reported that this system was fairly efficacious in Okinawa. In 1976, after reversion to Japan, study of T.B. surveillance control system was advised and introduced by Dr. Masakazu Aoki and Dr. Tooru Mori (JATA). By this modern system of surveillance, T.B. control is improved progressively in Okinawa.

Communicable Disease Control↗
PubMed2004

Mycobacterium tuberculosis (Mtb) isocitrate dehydrogenases show strong B cell response and distinguish vaccinated controls from TB patients.

Proteins released from Mycobacterium tuberculosis (Mtb) during late logarithmic growth phase are often considered candidate components of immunogenic or autolysis markers. One such protein is isocitrate dehydrogenase (ICD), a key regulatory enzyme in the citric acid cycle. We have evaluated the immunogenic properties of two isoforms of Mtb ICD and compared them with the control antigens heat-shock protein 60 and purified protein derivative (PPD). PPD lacks the sensitivity to distinguish between bacillus Calmette-Guérin (BCG)-vaccinated and tuberculosis (TB)-infected populations, and, therefore, epidemiological relevance of PPD in BCG-vaccinated regions is debatable. We show that Mtb ICDs elicit a strong B cell response in TB-infected populations and can differentiate between healthy BCG-vaccinated populations and those with TB. The study population (n = 215) was categorized into different groups, namely, patients with fresh infection (n = 42), relapsed TB cases (n = 32), patients with extrapulmonary TB (n = 35), clinically healthy donors (n = 44), nontuberculous mycobacteria patients (n = 30), and non-TB patients (culture negative for acid-fast bacteria but carrying other infections, n = 32). The Mtb ICDs showed statistically significant antigenic distinction between healthy BCG-vaccinated controls and TB patients (P < 0.0001) and those with other infections. Although extrapulmonary infections could not be discriminated from healthy controls by heat-shock protein 60 (P = 0.2177), interestingly, the Mtb ICDs could significantly (P < 0.0001) do so. Our results highlight the immunodominant, immunosensitive, and immunospecific nature of Mtb ICDs and point to an unusual property of this tricarboxylic acid energy cycle enzyme.

Antibody Formation↗
PubMed1992

Theoretical and methodological aspects of BCG vaccine from the discovery of Calmette and Guérin to molecular biology. A review.

The BCG vaccine has been used to prevent tuberculosis since 1921 and applied for immunostimulation in neoplasia since the 1960s. Both the preventive and immunostimulation effects have been evaluated and communicated with contradictory, positive and negative conclusions. For an objective evaluation and interpretation of the protective efficacy, effectiveness and efficiency of the BCG vaccination it must be considered that: (1) several BCG substrains have been developed in manufacturing laboratories that differ in the residual virulence which determines immunogenicity and reactogenicity; (2) various liquid and freeze-dried BCG vaccine production methods are used, resulting in different BCG viable units per dose; (3) quantitative bioassay methods are not yet being used for statistical quality control of the vaccine; (4) BCG products are applied in various demographical, epidemiological and socioeconomic conditions with different vaccination policies; (5) inadequate biostatistical models are often used to analyse efficacy, effectiveness and adverse reactions. The same conditions influence the precise evaluation of BCG immunostimulation in neoplasia. Recombinant DNA technology will modify production methods, and explain at the molecular level the mechanism of the protective effects BCG confers in tuberculosis and immunostimulation in neoplasia. High level laboratory techniques and biostatistical methods, based on probability logic and inductive inference, ensure appropriate experimental designs and the exact analysis of laboratory data and the results of vaccination policies. They will lead to the evaluation of the protective effect of BCG in order to reduce the BCG contradictions.

BCG Vaccine↗
PubMed2007

Intestinal helminth co-infection has a negative impact on both anti-Mycobacterium tuberculosis immunity and clinical response to tuberculosis therapy.

The impact of intestinal helminth infection on Mycobacterium tuberculosis (MTB)-specific immune responses during active tuberculosis (TB) is not known. We investigated the role of intestinal helminth infection in anti-MTB immunity by evaluating both cellular phenotype and cytokine profiles in patients with TB and patients with concomitant TB and intestinal helminth infection (TB + Helm) during TB therapy. Twenty-seven per cent of TB patients enrolled for the study were co-infected with at least one intestinal helminth. At baseline, absolute frequencies of leucocytes, monocytes and eosinophils from TB and TB + Helm patients differed from healthy subjects. Concomitant intestinal helminth infection in TB + Helm patients had a negative impact (P < 0.05) on absolute frequencies of CD3(+), CD4(+), CD8(+), natural killer (NK) T and CD4(+) CD25(high) T cell subsets when compared to either TB patients or healthy controls. Differences in CD4(+) T cell frequencies were accompanied by lower interferon (IFN)-gamma and elevated and sustained interleukin (IL)-10 levels in whole blood (WB) cultures from TB + Helm compared to TB patients. In addition to a depressed anti-MTB immunity, TB + Helm patients also presented with more severe radiological pulmonary disease, with a significant difference (P = 0.013) in the number of involved lung zones at the end of TB treatment. The above data may indicate that concomitant intestinal helminth infection in patients with newly diagnosed TB skews their cytokine profile toward a T helper 2 response, which could favour persistent MTB infection and a more protracted clinical course of the disease.

Adolescent↗
PubMed2001

[Levels of CEA, antibodies against mycobacterial antigens and ACE activity in serum and in BALF in patients with sarcoidosis, tuberculosis and lung cancer--preliminary results].

UNLABELLED: Assessment of CEA concentration, levels of the antibodies against mycobacterial antigens A60 and 38 kDa and ACE activity in serum and in BALF of the patients with sarcoidosis (n = 8), tuberculosis (n = 13) and lung cancer (n = 10) was performed. Nine healthy volunteers were referred to as the control group. Sarcoidosis and lung cancer were confirmed histopathologically. Diagnosis of tuberculosis was stated using the radiometric Bactec 460 system. Serum and BALF CEA concentration and IgG levels against A-60 and 38 kDa were measured by ELISA: IMx, Immunozym and Pathozyme, respectively. ACE activity was assayed by the spectrophotometric method. Statistically significant (p < 0.01) increase in BALF-ACE activity in patients with sarcoidosis compared to each group was observed. Serum level of antibodies against 38 kDa and serum ACE activity were specific for tuberculosis and sarcoidosis respectively, but their sensitivity were very poor. Serum CEA concentration was fairly specific for lung cancer but its sensitivity was not satisfactory. CONCLUSIONS: 1. Determination of BALF-ACE activity may be helpful in diagnosis of sarcoidosis but it is recommended to continue the study on more numerous groups of patients taking into consideration polymorphism in the ACE gene. 2. High level of antibodies against 38 kDa and ACE activity in serum are specific for tuberculosis and sarcoidosis respectively but both tests have restricted application because of their poor sensitivity. 3. Serum CEA concentration could be considered only as an auxiliary test in the diagnosis of lung cancer.

Adult↗
PubMed1997

Circulating profile of Th1 and Th2 cytokines in tuberculosis patients with different degrees of pulmonary involvement.

To investigate whether differences in the degree of pulmonary tuberculosis lesions could be accompanied by changes in the pattern of circulating cytokines, 29 untreated tuberculosis patients showing mild (n = 10), moderate (n = 5) or advanced (n = 14) pulmonary disease, and 12 age-matched healthy controls (mean +/- S.D., 36 +/- 15 years) were studied. ELISA methods for the evaluation of interferon-gamma, interleukin-2, interleukin-4, and interleukin-10 indicated that all patients had increased serum levels of the four cytokines in relation to controls. Mean titers of interferon-gamma and interleukin-2 in mild and moderate patients appeared higher than in those with advanced disease, whereas moderate and advanced patients showed the higher levels of IL-4 in comparison to mild cases. Raised levels of interleukin-10 were more prevalent in advanced disease, and statistically different from those in mild patients. This cytokine pattern may help to explain findings wherein mild tuberculosis is characterized by preserved cellular immune responses while advanced disease is accompanied by an impairment of such parameters.

Adolescent↗