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Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi.

Interferon (IFN)-gamma responsiveness to 12 purified protein derivative (PPD) and new tuberculin antigens from 9 species of mycobacteria was assessed, using a whole blood assay, in 616 young adults living in northern Malawi, where Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination provides no protection against pulmonary tuberculosis. The prevalence of IFN-gamma responsiveness was highest for PPDs of M. avium, M. intracellulare, and M. scrofulaceum (the MAIS complex). Correlations between responsiveness paralleled genetic relatedness of the mycobacterial species. A randomized, controlled trial was carried out, to assess the increase in IFN-gamma responsiveness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccination. The BCG-attributable increase in IFN-gamma response to M. tuberculosis PPD was greater for individuals with low initial responsiveness to MAIS antigens than for those with high initial responsiveness. Although not statistically significant, the trend is consistent with the hypothesis that prior exposure to environmental mycobacteria interferes with immune responses to BCG vaccination.

Antigens, Bacterial↗

[Models of tuberculosis control in countries with low tuberculosis prevalence].

To rationalize tuberculosis control in countries with low tuberculosis prevalence it is necessary to evaluate continuously some control measures and to propose suitable modifications. For years Czechoslovakia is taking part in the international research of methods of tuberculosis control; in compliance with the results of these studies its programme of tuberculosis control is being modified. Decision processes are more difficult, when measures till now applied should be limited or given up. In such cases it is necessary to evaluate not only the efficiency of defined health measures but also their possibilities of application, acceptability and influence on the tuberculosis situation in all. For the choice of appropriate models of tuberculosis control the application of experience from other countries should be regarded. However sometimes it is not possible to use this experience in the own country because there are obvious differences in other conditions. Mathematical simulation models may by of good help in the decision process answering the purpose of discerning the effect of different variants of the control measure on the epidemiological trends. For this purpose reliable statistic data should be available. To get such information a central tuberculosis register was established on CSR gathering data on new cases of tuberculosis, on relapses, on the further development of the cases of tuberculosis registered and on data concerning the quality of case-finding, diagnostics and therapy.

Adult↗

[Experimental study on prevention of diabetes complicated with tuberculosis by Mycobacterium vaccae].

OBJECTIVE: To study if Mycobacterium vaccae has any effect in prevention of rats with diabetes from tuberculosis. METHODS: Wistar rats with diabetes which were produced by injection of streptozotocin one week before were divided into four groups. Mycobacterium vaccae was injected into Wistar rats with diabetes and one month later H(37)R(v) was injected intravenously. The rats were sacrificed six weeks later to observe pathomorphologic changes in lung tissues. Indexes for evaluation included quantitative culture of Mycobacterium tuberculosis of lung tissue, tubercular lesion, count of Mycobacterium tuberculosis in alveolar macrophages and histopathological changes. RESULTS: Pathological change index of tubercular lesion, quantitative culture of Mycobacterium tuberculosis in lung tissue, count of Mycobacterium tuberculosis in alveolar macrophages were 2.5 +/- 0.7, (4.1 +/- 0.6) x 10(4) cfu, 2.6 +/- 0.9 respectively in group injected with Mycobacterium vaccae, while 3.3 +/- 0.5, (9.9 +/- 1.0) x 10(4) cfu, 7.2 +/- 0.7 respectively in the control group. Statistically significant differences were found between the two groups (P < 0.05, < 0.01, < 0.01 respectively). The histopathological changes of lung tissue in group of diabetes complicated with tuberculosis revealed that the lesions were predominant with necrosis, while in group injected with Mycobacterium vaccae, the lesions showed proliferation mainly. This indicated that Mycobacterium vaccae could decrease the damage to the lung tissue of the rat with diabetes by tubercle bacilli. CONCLUSION: Mycobacterium vaccae might play a role in prevention of rat with diabetes from tuberculosis.

Animals↗

Short-course chemotherapy for paediatric respiratory tuberculosis: 5-year report.

This report presents the 5-year follow-up of 137 children with respiratory tuberculosis enrolled in a randomised clinical trial of two different anti-tuberculosis regimens 9HR and 2HRZ3/4RH2. Both regimens had similar cure rates, with low relapse rates and mortality. Of 134 children followed up to 5 years, 86% had normal radiographs, with more sequelae in the 9HR group (15% vs. 1.5%, P < 0.01). One patient relapsed and there was one accidental death. Short-course chemotherapy in children is safe, effective and well tolerated, and leads to excellent long-term results, with a small proportion of children left with radiological sequelae.

Antitubercular Agents↗

Vascular endothelial growth factor levels in active pulmonary tuberculosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a mediator with potent angiogenic, mitogenic, and vascular permeability-enhancing activities that are specific for endothelial cells. Intense angiogenesis has been found in active pulmonary tuberculosis lesions. OBJECTIVES: To determine whether active pulmonary tuberculosis is associated with increased serum levels of VEGF compared with inactive tuberculosis and VEGF levels in healthy subjects, and to assess the changes in serum VEGF levels before and after therapy. DESIGN: Prospective clinical study. SETTING: Chest clinic of a university hospital, Eskisehir, Turkey. PATIENTS AND MEASUREMENTS: Serum VEGF levels of 44 patients with active pulmonary tuberculosis, 24 patients with inactive pulmonary tuberculosis, and 20 healthy subjects were determined. RESULTS: VEGF levels were increased in active pulmonary tuberculosis patients (mean [+/- SD] VEGF level, 598.03 +/- 298.25 pg/mL) compared to both inactive pulmonary tuberculosis patients (mean VEGF level, 296.98 +/- 115.31 pg/mL) and control subjects (mean VEGF level, 339.67 +/- 74.65 pg/mL). The increase in VEGF level observed in patients with active tuberculosis was statistically significant when compared with levels in two other groups (p < 0.001 for both). Serum VEGF levels were statistically different before treatment and after treatment in 10 patients who were observed from diagnosis to the end of treatment (p < 0.01). CONCLUSIONS: Increased serum VEGF levels may be an indicator of active pulmonary tuberculosis, since levels were higher in patients with active pulmonary tuberculosis and were lower after successful treatment. The role of VEGF-mediated angiogenesis in the pathogenesis and progression of pulmonary tuberculosis lesions should be further elucidated.

Adult↗

Practice based education to improve delivery systems for prevention in primary care: randomised trial.

OBJECTIVE: To examine the effectiveness of an intervention that combined continuing medical education with process improvement methods to implement "office systems" to improve the delivery of preventive care to children. DESIGN: Randomised trial in primary care practices. SETTING: Private paediatric and family practices in two areas of North Carolina. PARTICIPANTS: Random sample of 44 practices allocated to intervention and control groups. INTERVENTION: Practice based continuing medical education in which project staff coached practice staff in reviewing performance and identifying, testing, and implementing new care processes (such as chart screening) to improve delivery of preventive care. MAIN OUTCOME MEASURE: Change over time in the proportion of children aged 24-30 months who received age appropriate care for four preventive services (immunisations, and screening for tuberculosis, anaemia, and lead). RESULTS: The proportion of children per practice with age appropriate delivery of all four preventive services changed, after a one year period of implementation, from 7% to 34% in intervention practices and from 9% to 10% in control practices. After adjustment for baseline differences in the groups, the change in the prevalence of all four services between the beginning and the end of the study was 4.6-fold greater (95% confidence interval 1.6 to 13.2) in intervention practices. Thirty months after baseline, the proportion of children who were up to date with preventive services was higher in intervention than in control practices; results for screening for tuberculosis (54% v 32%), lead (68% v 30%), and anaemia (79% v 71%) were statistically significant (P < 0.05). CONCLUSION: Continuing education combined with process improvement methods is effective in increasing rates of delivery of preventive care to children.

Anemia↗

Antibodies to Mycobacterium paratuberculosis and nine species of environmental mycobacteria in Crohn's disease and control subjects.

Cultural and serological studies have provided limited, often conflicting, evidence of a role for mycobacteria in the pathogenesis of Crohn's disease. Interest has focussed on Mycobacterium paratuberculosis, previously considered to be common in the environment with no major role as a human pathogen. Whether a specific serum antibody response to mycobacteria occurs in Crohn's disease or ulcerative colitis was investigated. Sera from patients with Crohn's disease (n = 38), ulcerative colitis (n = 15), and a healthy control population (n = 30) were assayed in an enzyme linked immunosorbent assay (ELISA) using eight filtered sonicate mycobacterial preparations and a purified protein derivative made from the bovine tubercle bacillus. In addition, IgG, IgM, and IgA levels to M paratuberculosis were determined in sera from patients with active (n = 24) or inactive (n = 29) Crohn's disease and the control populations. There was strong evidence of contact with environmental mycobacteria in all patients and control populations, with the greatest responses to preparations of M avium, M tuberculosis, and M kansasii. A large proportion of patients with Crohn's disease had antibodies that bound most antigens tested but there were no statistical differences between these values and those of the control population. Similarly, there were no differences in antibody levels to M paratuberculosis in patient and control groups. Although a subset of patients with active Crohn's disease (25%) had IgG concentrations that exceeded the control mean by more than 2 SD, this phenomenon may not be specific to Crohn's disease: 20% of a small group of patients with coeliac disease had similarly raised IgG levels to M paratuberculosis. These findings do not provide serological evidence of a role for this organism in the pathogenesis of Crohn's disease.

Antibodies, Bacterial↗

Diethylcarbamazine-related antimicrobial activity in Mycobacterium tuberculosis-infected blood.

Previous studies have suggested that diethylcarbamazine (DEC), a drug used for filariasis control, may be useful in the treatment of mycobacterial infections. In this experiment, Mycobacterium tuberculosis was added to blood samples from two groups (healthy and diabetic) of adult non-smoking donors. Portions of each sample were tested with and without DEC at clinically achievable levels. Statistically significant DEC-related percentage decreases in BACTEC growth index counts were noted for each group (Wilcoxon one-sample signed-rank tests, alpha = 0.05, two-tailed). These results suggest that administration of DEC for filariasis control could have a positive impact on tuberculosis control.

Antitubercular Agents↗

Proposing indicators for evaluation of tuberculosis control programmes in large cities based on the experience of Barcelona.

OBJECTIVE: To evaluate the effectiveness of the Barcelona Tuberculosis (TB) Control Programme and to propose evaluation indicators. MATERIALS AND METHODS: Using quantitative indicators, the results and impact of the programme over the period 1987 to 1999 were evaluated. Statistical analysis was based on a description of indicators, including tests for trends, and on the evolution of the incidence. RESULTS: The incidence of tuberculosis rose between 1987 and 1991 (P = 0.10), and fell between 1991 and 1999 (P < 0.001). During the study period statistically significant improvements were observed in the percentage of cases notified by the medical profession, adherence to treatment and the percentage of cases on directly observed treatment (DOT), and meningitis among children aged 0 to 4 years fell notably. However, diagnostic delay in smear-positive cases and the percentage of cases whose contacts were examined did not vary significantly. The evaluation indicated an average annual decline in tuberculosis incidence of 6.7%, and rates of adherence to treatment (94.5% among smear-positive cases) achieved their objectives. The average median diagnostic delay (36 days) and the percentage of cases with contacts examined (mean 59.8%) were rather less optimistic. CONCLUSIONS: The results of the evaluation were in general positive. Decline in incidence, meningitis in children, treatment adherence rates, diagnostic delay and percentage of cases with studied contacts were considered the best indicators for evaluation of TB programmes.

Child↗

[Angiotensin-converting enzyme (ACE) in sarcoidosis, tuberculosis, silicosis, and coal mining workers].

We studied the seric activity of the angiotensin converting enzyme (ACE) in 19 patients with sarcoidosis, 14 tuberculosis, 16 silicosis and 15 workers of coal mining without silicosis and other concomitant diseases, in order to assess its usefulness as orientative parameter for the differential diagnosis of these processes. We found significantly increased values with respect to the control group in all of them: control group (40.84 +/- 13.06 U/l), sarcoidosis (57.77 +/- 16.47 U/l), tuberculosis (46.85 +/- 10.25 U/l), silicosis (61.50 +/- 21.40 U/l), miners (71.50 +/- 12.48 U/l). We did not detect any statistically significant differences between the several diagnostic groups except for miners and tuberculosis (p = 0.04). We conclude that this parameter is hot very useful for the diagnostic orientation of these processes.

Adult↗

Recent studies in the epidemiology of tuberculosis, based on the risk of being infected with tubercle bacilli.

This review describes recent epidemiological studies, based upon the risk of infection with tubercle bacilli. In the Netherlands the risk of infection has been decreasing steeply and exponentially for many years, but in some developing countries there was little secular trend in the absence of intensive control measures. Variations in the risk of infection with age are being examined. A comprehensive statistical analysis has shown that the major risk of development of tuberculosis is following a recent primary infection; the risk is smaller following reinfection of a previously infected subject, and is very small indeed, in the absence of reinfection, if the primary infection took place more than 5 years previously.

Adolescent↗

National survey of endodontists and selected patient samples: infectious diseases and attitudes toward infection control.

A survey was conducted of 591 patients from endodontic practices located in six large municipalities in the United States. A comparison was made between the self-reported incidence of transmissible diseases from patients medical histories to national statistics for the incidence of hepatitis B, herpes, tuberculosis, and HIV/AIDS. A national survey of 422 endodontists was also conducted. This survey was used to determine the beliefs and attitudes of practicing endodontists toward infection control techniques and infectious diseases. Compared with previous surveys, a trend toward increasing use of the hepatitis B vaccine, gloves, and greater acceptance of medically compromised patients was found.

Attitude of Health Personnel↗

National survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection.

BACKGROUND: Cases of severe and fatal liver injury were reported after a 2-month course of rifampin-pyrazinamide therapy was recommended in 2000 as an alternative to isoniazid for treatment of latent tuberculosis infection. We estimated rates of rifampin-pyrazinamide-associated liver injury and compared these with historical rates for isoniazid. METHODS: We conducted a survey of state and city tuberculosis programs and other health care settings in the United States where rifampin-pyrazinamide was prescribed. The number of rifampin-pyrazinamide therapy initiations was collected, as well as the number of occurrences of (1) asymptomatic aspartate aminotransferase serum concentration >5 times the upper limit of normal, (2) symptomatic hepatitis (in which the patient was not hospitalized), (3) hospitalization for liver injury, (4) death with liver injury, and (5) treatment completion. We also searched a national pharmacy claims database (Verispan). Rates of these events were calculated. RESULTS: Among 139 programs, 110 (79%) responded; 87 (79%) had initiated rifampin-pyrazinamide therapy for a total of 8087 patients between January 2000 and June 2002. Rates per 1000 rifampin-pyrazinamide therapy initiations during this period were 25.6 (95% confidence interval [CI], 22.3-29.3) for asymptomatic aspartate aminotransferase level >5 times the upper limit of normal and 18.7 (95% CI, 15.9-21.9) for hepatitis. Seven fatalities and 23 hospitalizations occurred, with rates of 0.9 (95% CI, 0.4-1.9) and 2.8 (95% CI, 1.8-4.3) per 1000 rifampin-pyrazinamide therapy initiations, respectively. Of 8087 patients, 64% completed rifampin-pyrazinamide therapy. The Verispan search revealed 1 rifampin-pyrazinamide-associated hospitalization (2.9 hospitalizations per 1000 rifampin-pyrazinamide therapy initiations; 95% CI, 0.1-18.4) and no deaths. Articles on the use of isoniazid therapy for latent tuberculosis infection that were published after 1990 reported fatality rates of 0.0-0.3 deaths per 1000 persons. CONCLUSIONS: Rates of liver injury, hospitalization, and death associated with rifampin-pyrazinamide therapy exceed rates reported for isoniazid therapy. Because earlier randomized trials of rifampin-pyrazinamide lacked adequate statistical power to detect fatal events, the Centers for Disease Control and Prevention recommends that rifampin-pyrazinamide generally should not be used for treatment of latent tuberculosis infection.

Antitubercular Agents↗

Tuberculosis and nonsteroidal anti-inflammatory drugs.

In 1980 and 1982 two case reports documented reactivation of pulmonary tuberculosis in patients who had used nonsteroidal anti-inflammatory drugs (NSAIDs). A case-control study was designed to test the hypothesis that such an association does exist. Data for 38 patients were obtained from the patients' family physicians, and each patient was matched with a control from the same practice for age, sex, race and length of time in that practice. A statistically significant relation was found between the reactivation of tuberculosis and the use of NSAIDs. However, further research is imperative to determine whether the association is direct, indirect or secondary to an unknown factor. Physicians should keep in mind that NSAIDs are potent anti-inflammatory agents and may thus activate, spread and mask infections.

Aged↗

Prevalence of drug resistance in Thai human immunodeficiency virus seropositive tuberculosis patients.

The emergence of drug resistant tuberculosis has been reported from many countries which have had epidemics of human immunodeficiency virus (HIV) infection. This study was conducted at the Central Chest Hospital, Thailand in order to determine the prevalence of drug resistance before treatment in Thai HIV-infected tuberculosis patients. From the Statistics and Registration Unit, pulmonary tuberculosis patients with HIV seropositivity were matched in terms of age and gender with control cases who attended the tuberculosis clinic on the same day. Results of sensitivity test were obtained from record cards in the Microbiology Section. The method for determining the sensitivity test was absolute concentration. During the study period from January 1988 to December 1993, 798 patients were registered as having tuberculosis and HIV infection. Only 406 sensitivity tests were available before treatment and resisted to Isoniazid 56 (13.8%), rifampicin 36 (8.9%), ethambutol 6 (1.5%), streptomycin 64 (15.8%) and Multidrug resistant (MDR)- TB 11 (2.7%). In the control group, 475 tests were available and resisted to isoniazid 61 (12.8%), rifampicin 52 (10.9%), ethambutal 2 (0.4%), streptomycin 46 (9.7%) and MDR-TB 13 (2.7%). The prevalence of resistance to each drug was not significantly different except for streptomycin. We concluded that the prevalence of antituberculous drug resistance among Thai HIV-infected tuberculosis patients was not higher than among general tuberculosis patients.

Adolescent↗