Tsi Shu Huang

High prevalence of latent tuberculosis infection in patients in end-stage renal disease on hemodialysis: Comparison of quantiFERON-TB GOLD, ELISPOT, and tuberculin skin test

Background:Individuals with end-stage renal disease (ESRD) are 10- to 25-fold more likely than immunocompetent people to develop active tuberculosis (TB) and are candidates for being treated for latent TB infection (LTBI). However, diagnosis using the tuberculin skin test (TST) is doubly difficult due to cutaneous anergy and cross-reactions with Bacille–Calmette–Guérin (BCG) vaccination.Materials and Methods:This was a prospective, doublematched, cohort study in which 32 ESRD patients and 32 age-matched, healthy controls were enrolled. The TST and two new interferon-γ blood tests, QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (ELISPOT), were performed. The subjects were followed up 2 years for active TB disease. ELISPOT was done in ESRD patients only.Results:Compared to the healthy controls, a high prevalence of LTBI was found in the ESRD patients by TST (62.5%, 95% confidence interval [CI] 43.7–78.9), QFT-G (40.0%, 95% CI 22.7–59.4), and ELISPOT (46.9%, 95% CI 29.1–65.3). Agreement was moderate (kappa [κ] = 0.53) for QFT-G and ELISPOT but only slight between TST and QFT-G (κ = 0.25) and fair between TST and ELISPOT (κ = 0.32). ESRD (p = 0.03) and diabetes mellitus (p = 0.04) were significant risk factors for QFT-G positivity on the multivariable analysis. The overall rate of active TB was 1.66 cases per 100 person-years (pys), with the rate higher in patients with ESRD (3.53 per 100 pys) and those with positive (3.40 per 100 pys) and indeterminate QFT results (30.16 per 100 pys), although the difference was not statistically significant. Sensitivity, specificity, and positive and negative predictive values of QFT-G for active TB was 100%, 62.1%, 8.3% and 100%.Conclusion:This pilot study is the first to compare QFT-G, ELISPOT, and TST in ESRD patients on hemodialysis and demonstrates a high prevalence of LTBI in this population. In our study, the QFT-G was the more accurate method for identifying those truly infected with Mycobacterium tuberculosis, even in BCG-vaccinated individuals.

Comparison of the interferon- gamma release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers.

Health care workers are at increased risk of Mycobacterium tuberculosis infection. The tuberculin skin test (TST) is frequently false positive in BCG-vaccinated health care workers. QuantiFERON-TB GOLD (QFT-G) is a sensitive and specific interferon-γ release assay unaffected by BCG vaccination. This study compared TST and QFT-G in the diagnosis of latent TB infection in BCG-vaccinated health care workers. 39 health care workers exposed to a smear-positive TB patient were enrolled. Initial TST was positive in 33 (84.6%) cases, but only 4 (10.2%) cases using QFT-G. TST conversion occurred in 2/6 (33.3%), compared to 4/32(12.5%), cases using QFT-G. A higher proportion of QFT converters was associated with intimate contact, although not reaching statistical significance. Face-to-face contact >1 h was significantly associated with QFT-G conversion ≥0.7 IU/ml (OR 8.63, 95%CI 1.08–69.07, p=0.04). Agreement between TST and QFT-G was 18.0%, (κ: −0.03). Concordance between TST and QFT (≥0.35 IU/ml) conversion was 40.0%(κ=−0.40), and 60.0%(κ=0.00) if QFT ≥0.7 IU/ml was used. Agreement increased with increasing TST cut-offs. TST is not useful in contact investigation among BCG-vaccinated health care workers, in an area with intermediate burden of TB. QFT may provide additional information for the diagnosis and strategic management of preventive treatment of LTBI in BCG-vaccinated health care workers in a country with intermediate burden of TB.

Extent of antibiotic use in Taiwan shown by antimicrobial activity in urine

Taiwan has high prevalence of antibiotic resistant, community-acquired respiratory pathogens. We investigated whether there was a high frequency of antibiotic use in the community. Antimicrobial activity in urine was detected in 55.2% of 1182 patients on arrival at an emergency department, 25.1% of 203 internal medicine out-patients, 7.6% of 471 high school students, and 7.4% of 202 people at a centre for senior citizens.

In vitro activities of linezolid against clinical isolates of Mycobacterium tuberculosis complex isolated in Taiwan over 10 years.

ABSTRACT Significant increases in the MIC90s of linezolid in multidrug-resistant Mycobacterium tuberculosis isolates were seen between the baseline period of 2001 to 2003 (0.5 μg/ml) and 2004 (2 μg/ml). The MICs were 4 μg/ml in three strains. Both fluoroquinolones (except levofloxacin) and kanamycin were found to have statistically significant degrees of concordance with linezolid.

Differential diagnosis of tuberculous and malignant pleurisy using pleural fluid adenosine deaminase and interferon gamma in Taiwan

Accurately differentiating tuberculous pleurisy from lung cancer is important for disease management but difficult using conventional laboratory methods. This study assessed the value of adenosine deaminase (ADA) and interferon gamma (IFN-γ) for differentiating the two conditions in a region of Taiwan with a high prevalence of tuberculosis. The study population comprised patients with lymphocytic exudative pleural effusions: tuberculous (n=24) and malignant (n=42). Mean levels of ADA and IFN-γ in pleural fluid, measured with commercial standardized kits, were significantly higher for tuberculous than for malignant pleurisy (p<0.001 for both). For differentiating the two effusions, results for ADA versus IFN-γ were: sensitivity, 70.8% versus 91.7%; specificity, 95.2% versus 97.6%; positive predictive value, 89.5% versus 96.7%; and negative predictive value, 85.1% versus 95.3%. IFN-γ allows precise diagnosis of pleural tuberculosis, but ADA is easier to use, has a low cost, and results are quickly available. Our study confirms previous studies and extends the usefulness of these diagnostic methods to a wider group of clinical laboratories by showing the reliability of standardized relatively inexpensive commercial kits. We recommend that initial ADA screening be used in conjunction with IFN-γ measurements for differential diagnosis of tuberculous pleurisy.

Role of genotype and precore/basal core promoter mutations of hepatitis B virus in patients with chronic hepatitis B with acute exacerbation

Objctive. The results of long-term, follow-up studies show that the severity and frequency of acute exacerbation of chronic hepatitis B virus (HBV) are associated with the development of liver cirrhosis in chronic HBV infection. The aim of this study was to investigate the relationship between virological factors of HBV and the severity of acute exacerbation. Material and methods. Fifty-one chronic hepatitis B patients with symptomatic acute exacerbation without antiviral therapy were enrolled in the study. Genotype of HBV was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Precore (A1896) and basal core promoter (BCP) mutations (T1762 & A1764) were determined by PCR and direct sequencing. Results. Thirty-nine patients had genotype B, 11 patients had genotype C, and 1 patient had an unclassified genotype. Thirty-two patients had precore mutation and 24 patients had BCP mutation. After adjusting for age, gender, aspartate aminotransferase (ASAT) level, albumin level, and platelet count by multiple logistic regression test, precore mutation had a protective effect on the occurrence of hepatic decompensation (p=0.046), and genotype and BCP mutations were not associated with the occurrence of hepatic decompensation. Conclusions. HBV precore mutation may confer less severe liver disease during acute exacerbation of chronic HBV. Genotype and BCP mutations did not have a significant association with the occurrence of hepatic decompensation.

Antimicrobial Resistance of Rapidly Growing Mycobacteria in Western Taiwan: SMART Program 2002

BACKGROUND/PURPOSE To understand the resistance patterns of rapidly growing mycobacteria (RGM) in Taiwan, antimicrobial resistance of clinical isolates was determined as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. METHODS During the period from January 2002 to December 2003, clinical isolates were collected from eight hospitals located on the west side of Taiwan and one reference laboratory. Broth microdilution minimum inhibitory concentrations of 11 antimicrobial agents were determined for 312 clinical isolates of RGM, including the Mycobacterium fortuitum group (110 isolates), Mycobacterium abscessus group (168 isolates), and Mycobacterium chelonae group (34 isolates). RESULTS Nearly all of the RGM were susceptible to amikacin and ofloxacin (= 90%) and resistant to doxycycline (less than 3% susceptible). Tobramycin showed similar in vitro activity against the M. fortuitum and M. chelonae (77%) groups, but was less active against the M. abscessus group (58%). Ciprofloxacin was active mainly against M. fortuitum (95%). Nearly all RGM were resistant to erythromycin and doxycycline. However, around half of the RGM isolates remained susceptible to minocycline (50-54%). Clarithromycin was active against the M. abscessus group (53% susceptible), with a high rate of resistance in the M. chelonae (38% susceptible) and M. fortuitum (15% susceptible) group. Cefoxitin was more active against the M. fortuitum group (65%) than the other two RGM (40-44%), and les than 40% of the RGM isolates remained susceptible to imipenem (21-38%). CONCLUSION The resistance of RGM in Taiwan is not as high as previously reported (notably for tobramycin, ciprofloxacin and cefoxitin), but reduction in the susceptibility rates of clarithromycin and imipenem for the M. fortuitum and M. abscessus groups demonstrates the importance of in vitro susceptibility testing of clinically important isolates, as susceptibility may differ in different geographical areas, even regionally, and over time.

Detection and identification of human parechoviruses from clinical specimens

Human parechovirus (HPeV) may cause various illnesses; however, technologists and clinicians often overlook it. This study, designed to detect HPeV in 3124 clinical specimens from 2849 patients between January and August 2007, presents the first report of HPeVs confirmed by RNA sequences in Taiwan. Reverse transcriptase polymerase chain reaction (RT-PCR) and phylogenetic tree analysis identified the isolates as HPeV1 (n = 5), HPeV3 (n = 1), and HPeV4 (n = 2) from 6 children. Although the prevalence is low, HPeVs do cause significant clinical manifestations in children. Phylogenetic analysis has separated the 8 HPeV1 strains as a new lineage from the prototype strain (L02971) in evolutionary transition. Clinicians and technologists should have a high index of suspicion and apply RT-PCR for identification when presented with slower Enterovirus-like cytopathic effect (CPE) in cell cultures and negative or equivocal results of staining with indirect immunofluorescence assay, particularly if the CPE is larger, smoother, and more refractive and relatively slow.

Streptococcus Suis Meningitis with Ventriculoperitoneal Shunt Infection and Spondylodiscitis

Streptococcus suis is a zoonotic pathogen which causes meningitis, bacteremia, and endocarditis in pigs. Human infection is rare and often presents as meningitis with the sequela of permanent deafness and endocarditis. Previous cases were reported from pig-rearing countries such as Holland and Hong Kong. We report a 55-year-old bedridden man with S. suis meningitis complicated with ventriculoperitoneal shunt infection and lumbar spine spondylodiscitis. He presented with fever, delirium, neck stiffness, lower leg weakness and sudden onset hearing loss for several days. He was successfully treated with intravenous antibiotics, ventriculoperitoneal shunt replacement, lumbar spinal laminotomy and discectomy. Cerebrospinal fluid culture initially misidentified the organism as Streptococcus acidominimus, and S. suis was later identified by 16S rRNA sequencing. Misidentification of the microbiological findings may lead to a failure to correctly diagnose this disease. S. suis meningitis should be included in the differential diagnosis of patients with meningitis and sudden hearing loss.

The Sour Taste-Modifying Protein (Miraculin), Tyrosinase Inhibitors and Antioxidants from Synsepalum dulcificum

There are four basic tastes, including sweet, sour, bitter and salty. Any other taste is merely combination of these four. Red berries of Synsepalum dulcificum, which is an evergreen shrub native of tropical West Africa, have a property in modifying taste by switching sour into a sweet taste remarkably, so the berry has been called miracle fruit. Among all taste proteins, there is one in particular - miraculin - which lacks taste completely when absorbed on its own but has the power of modifying a disagreeable taste into a pleasant one. The active miraculin causes citric acid, ascorbic acid, acetic acid and hydrochloric acid which are normally sour to be perceived as sweet after being held in the mouth. In this review, we demonstrated the miracle fruit development and miraculin identification, including glycosylation and protein structure. We also extracted the fruit of S. dulcificum with methanol (MeOH), and the pulp with chloroform (CHCl3), respectively. All obtained extracts were evaluated for their tyrosinase inhibition and free radical scavenging. The anti-tyrosinase effects were to calculate the hydroxylation of L-tyrosine to L-dopa according to in vitro mushroom tyrosinase assay. The antioxidant potential was evaluated using the following in vitro method: scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. This was the first time to reveal these bioactivities from this species plant to date.