Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

<p>Abstract</p> <p>Background</p> <p>Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries.</p> <p>Methods</p> <p>Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE).</p> <p>Results</p> <p>CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (<it>P </it>< 0.0001 and <it>P </it>= 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement.</p> <p>Conclusions</p> <p>CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading.</p

Prevalence and Risk Factors for Tuberculosis Infection among Hospital Workers in Hanoi, Viet Nam

BACKGROUND: Transmission of tuberculosis (TB) to health care workers (HCWs) is a global issue. Although effective infection control measures are expected to reduce nosocomial TB, HCWs' infection has not been assessed enough in TB high burden countries. We conducted a cross-sectional study to determine the prevalence of TB infection and its risk factors among HCWs in Hanoi, Viet Nam. METHODOLOGY/PRINCIPAL FINDINGS: A total of 300 HCWs including all staff members in a municipal TB referral hospital received an interferon-gamma release assay (IGRA), QuantiFERON-TB Gold In-Tube(TM), followed by one- and two-step tuberculin skin test (TST) and a questionnaire-based interview. Agreement between the tests was evaluated by kappa statistics. Risk factors for TB infection were analyzed using a logistic regression model. Among the participants aged from 20 to 58 years (median = 40), prevalence of TB infection estimated by IGRA, one- and two-step TST was 47.3%, 61.1% and 66.3% respectively. Although the levels of overall agreement between IGRA and TST were moderate, the degree of agreement was low in the group with BCG history (kappa = 0.29). Working in TB hospital was associated with twofold increase in odds of TB infection estimated by IGRA. Increased age, low educational level and the high body mass index also demonstrated high odds ratios of IGRA positivity. CONCLUSIONS/SIGNIFICANCE: Prevalence of TB infection estimated by either IGRA or TST is high among HCWs in the hospital environment for TB care in Viet Nam and an infection control program should be reinforced. In communities with heterogeneous history of BCG vaccination, IGRA seems to estimate TB infection more accurately than any other criteria using TST

Superiority of Nebulized Corticosteroids over Dry Powder Inhalers in Certain Patients with Cough Variant Asthma or Cough-Predominant Asthma

Background: The particle distribution might differ between nebulizer therapy and metered-dose inhaler (MDI) or dry powder inhaler (DPI) therapy because the particles repeatedly enter/re-enter the airways with the nebulizer. Inhaled corticosteroids (ICS) were administered with a nebulizer to assess the benefit of changes in the distribution of particles in patients with cough variant asthma (CVA) and cough-predominant asthma (CPA). Methods: Patients whose symptoms were not controlled by their current therapy were enrolled. In patients receiving high-dose ICS by MDI or DPI (ICS-MDI/DPI), steroid therapy was switched to 1,320 μg/day of nebulized dexamethasone (1,600 μg as dexamethasone sodium phosphate) (chronic steroid-independent group). In patients receiving systemic steroids regardless of their ICS-MDI/DPI therapy, nebulized dexamethasone was added and any concurrent ICS-MDI/DPI therapy was halted to detect a steroid-sparing effect (chronic steroid-dependent group). In patients with acute exacerbation of CVA or CPA and persistent symptoms despite systemic corticosteroids, nebulized dexamethasone was added to assess its effect (acute group). Results: Superior symptom control was achieved in 10 out of 12 steroid-independent patients, 3 out of 6 steroid-dependent patients, and all 7 acute patients. Conclusions: Delivery of ICS via a nebulizer has advantages over ICS-MDI/DPI in some patients with CVA or CPA

Identification of katG Mutations Associated with High-Level Isoniazid Resistance in Mycobacterium tuberculosis▿ †

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates

Characterization of a Trinucleotide Repeat Sequence (CGG)(5) and Potential Use in Restriction Fragment Length Polymorphism Typing of Mycobacterium tuberculosis

The genomes of 28 bacterial strains, including mycobacterial species Mycobacterium tuberculosis and Mycobacterium bovis, were analyzed for the presence of a special class of microsatellite, that of trinucleotide repeat sequences (TRS). Results of a search of all 10 possible TRS motifs (i.e., CCT, CGG, CTG, GAA, GAT, GTA, GTC, GTG, GTT, and TAT) with five or more repeating units showed that (CGG)(5) was highly represented within the genomic DNA of M. tuberculosis and M. bovis. Most of the (CGG)(5) repeats in the genome were within the open reading frames of two large gene families encoding PE_PGRS and PPE proteins that have the motifs Pro-Glu (PE) and Pro-Pro-Glu (PPE). (CGG)(5)-probed Southern hybridization showed that some mycobacterial species, such as Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium szulgai, possess many copies of (CGG)(5) in their genomes. Analysis of clinical isolates obtained from Tokyo and Warsaw with both IS6110 and (CGG)(5) probes showed that there is an association between the fingerprinting patterns and the geographic origin of the isolates and that (CGG)(5) fingerprinting patterns were relatively more stable than IS6110 patterns. The (CGG)(5) repeat is a unique sequence for some mycobacterial species, and (CGG)(5) fingerprinting can be used as an epidemiologic method for these species as well as IS6110 fingerprinting can. If these two fingerprinting methods are used together, the precise analysis of M. tuberculosis isolates will be accomplished. (CGG)(5)-based fingerprinting is particularly useful for M. tuberculosis isolates with few or no insertion elements and for the identification of other mycobacterial species when informative probes are lacking

Detection of Multidrug Resistance in Mycobacterium tuberculosis

We developed a DNA sequencing-based method to detect mutations in the genome of drug-resistant Mycobacterium tuberculosis. Drug resistance in M. tuberculosis is caused by mutations in restricted regions of the genome. Eight genome regions associated with drug resistance, including rpoB for rifampin (RIF), katG and the mabA (fabG1)-inhA promoter for isoniazid (INH), embB for ethambutol (EMB), pncA for pyrazinamide (PZA), rpsL and rrs for streptomycin (STR), and gyrA for levofloxacin, were amplified simultaneously by PCR, and the DNA sequences were determined. It took 6.5 h to complete all procedures. Among the 138 clinical isolates tested, 55 were resistant to at least one drug. Thirty-four of 38 INH-resistant isolates (89.5%), 28 of 28 RIF-resistant isolates (100%), 15 of 18 EMB-resistant isolates (83.3%), 18 of 30 STR-resistant isolates (60%), and 17 of 17 PZA-resistant isolates (100%) had mutations related to specific drug resistance. Eighteen of these mutations had not been reported previously. These novel mutations include one in rpoB, eight in katG, one in the mabA-inhA regulatory region, two in embB, five in pncA, and one in rrs. Escherichia coli isolates expressing individually five of the eight katG mutations showed loss of catalase and INH oxidation activities, and isolates carrying any of the five pncA mutations showed no pyrazinamidase activity, indicating that these mutations are associated with INH and PZA resistance, respectively. Our sequencing-based method was also useful for testing sputa from tuberculosis patients and for screening of mutations in Mycobacterium bovis. In conclusion, our new method is useful for rapid detection of multiple-drug-resistant M. tuberculosis and for identifying novel mutations in drug-resistant M. tuberculosis

Exploration of energization and radiation in geospace (ERG): challenges, development, and operation of satellite systems

Abstract The exploration of energization and radiation in geospace (ERG) satellite, nicknamed “Arase,” is the second satellite in a series of small scientific satellites created by the Institute of Space and Astronautical Science of the Japan Aerospace Exploration Agency. It was launched on December 20, 2016, by the Epsilon launch vehicle. The purpose of the ERG project is to investigate how high-energy (over MeV) electrons in the radiation belts surrounding Earth are generated and lost by monitoring the interactions between plasma waves and electrically charged particles. To measure these physical processes in situ, the ERG satellite traverses the heart of the radiation belts. The orbit of the ERG is highly elliptical and varies due to the perturbation force: the apogee altitude is approximately 32,200–32,300 km, and the perigee altitude is 340–440 km. In this study, we introduce the scientific background for this project and four major challenges that need to be addressed to effectively carry out this scientific mission with a small satellite: (1) dealing with harsh environmental conditions in orbit and electromagnetic compatibility issues, (2) spin attitude stabilization and avoiding excitation of the libration by flexible structures, (3) attaining an appropriate balance between the mission requirements and the limited resources of the small satellite, and (4) the adaptation and use of a flexible standardized bus. In this context, we describe the development process and the flight operations for the satellite, which is currently working as designed and obtaining excellent data in its mission