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Tang H.-L.,National Chung Hsing University | Tang H.-L.,China Medical University at Taichung | Chiang M.-K.,National Chung Cheng University | Liou W.-J.,Chung Shan Medical University | And 8 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2010

Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n=94) were more likely to be terW +-iutA +-rmpA +-silS + than those related to non-abscess infections (n=113) (62% vs. 27%; p<0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p<0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation. © 2010 Springer-Verlag. Source


Wu S.-L.,A-Life Medical | Wu S.-L.,Center for Research and Diagnostics | Wang S.-C.,National Health Research Institute | Tsou H.-H.,National Health Research Institute | And 10 more authors.
PLoS ONE | Year: 2013

Background and Objectives:Heroin-dependent patients typically contract hepatitis C virus (HCV) at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT) is a major treatment regimen for opioid dependence. HCV infection may affect methadone metabolism but this has rarely been studied. In our current study, we aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan.Methods:A total of 366 MMT patients were recruited. The levels of plasma hepatitis B virus (HBV), HCV, human immunodeficiency virus (HIV) antibodies (Ab), liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were measured along with the urine morphine concentration and amphetamine screening.Results:Of the 352 subjects in our cohort with HCV test records, 95% were found to be positive for plasma anti-HCV antibody. The liver functional parameters of AST (Wilcoxon Rank-Sum test, P = 0.02) and ALT (Wilcoxon Rank-Sum test, P = 0.04), the plasma methadone concentrations (Wilcoxon Rank-Sum test, P = 0.043) and the R-enantiomer of methadone concentrations (Wilcoxon Rank-Sum test, P = 0.032) were significantly higher in the HCV antibody-positive subjects than in the HCV antibody-negative patients, but not the S-EDDP/methadone dose ratio. The HCV levels correlated with the methadone dose (β̂ = 14.65 and 14.13; P = 0.029 and 0.03) and the S-EDDP/methadone dose ratio (β̂ = -0.41 and -0.40; P = 0.00084 and 0.002) in both univariate and multivariate regression analyses.Conclusions:We conclude that HCV may influence the methadone dose and plasma S-EDDP/methadone dose ratio in MMT patients in this preliminary study. © 2013 Wu et al. Source


Koh X.P.,University of Malaya | Chiou C.S.,Center for Research and Diagnostics | Ajam N.,University of Malaya | Watanabe H.,Japan National Institute of Infectious Diseases | And 2 more authors.
BMC Infectious Diseases | Year: 2012

Background: Shigellosis is a major public health concern worldwide, especially in developing countries. It is an acute intestinal infection caused by bacteria of the genus Shigella, with a minimum infective dose as low as 10-100 bacterial cells. Increasing prevalence of Shigella sonnei as the etiologic agent of shigellosis in Malaysia has been reported. As there is limited information on the genetic background of S. sonnei in Malaysia, this study aimed to characterize Malaysian S. sonnei and to evaluate the prospect of using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for subtyping of local S. sonnei.Methods: Forty non-repeat clinical strains of S. sonnei isolated during the years 1997-2000, and 2007-2009 were studied. The strains were isolated from stools of patients in different hospitals from different regions in Malaysia. These epidemiologically unrelated strains were characterized using biotyping, antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE) and MLVA.Results: The two biotypes identified in this study were biotype a (n = 29, 73%) and biotype g (n = 11, 27%). All the 40 strains were sensitive to kanamycin, ceftriaxone and ciprofloxacin. Highest resistance rate was observed for streptomycin (67.5%), followed by tetracycline (40%) and trimethoprim-sulfamethoxazole (37.5%). All the S. sonnei biotype g strains had a core resistance type of streptomycin - trimethoprim-sulfamethoxazole - tetracycline whereas the 29 biotype a strains were subtyped into eight resistotypes. All the strains were equally distinguishable by PFGE and MLVA. Overall, PFGE analysis indicated that S. sonnei biotype a strains were genetically more diverse than biotype g strains. Cluster analysis by MLVA was better in grouping the strains according to biotypes, was reflective of the epidemiological information and was equally discriminative as PFGE.Conclusions: The S. sonnei strains circulating in Malaysia throughout the period studied were derived from different clones given their heterogeneous nature. MLVA based on seven selected VNTR loci was rapid, reproducible and highly discriminative and therefore may complement PFGE for routine subtyping of S. sonnei. © 2012 Koh et al.; licensee BioMed Central Ltd. Source


Lin J.-H.,Center for Research and Diagnostics | Lin J.-H.,National Taiwan Ocean University | Chiu S.-C.,Center for Research and Diagnostics | Chiu S.-C.,National Yang Ming University | And 8 more authors.
PLoS ONE | Year: 2011

Background: Many studies concentrate on variation in the hemagglutinin glycoprotein (HA) because of its significance in host immune response, the evolution of this virus is even more complex when other genome segments are considered. Recently, it was found that cytotoxic T lymphocytes (CTL) play an important role in immunity against influenza and most CTL epitopes of human influenza viruses were remarkably conserved. The NP gene has evolved independently in human and avian hosts after 1918 flu pandemic and it has been assigned a putative role as a determinant of host range. Methods and Findings: Phylodynamic patterns of the genes encoding nucleoprotein (NP) of influenza A viruses isolated from 1979-2009 were analyzed by applying the Bayesian Markov Chain Monte Carlo framework to better understand the evolutionary mechanisms of these Taiwanese isolates. Phylogenetic analysis of the NP gene showed that all available H3 worldwide isolates collected so far were genetically similar and divided into two major clades after the year 2004. We compared the deduced amino acid sequences of the NP sequences from human, avian and swine hosts to investigate the emergence of potential adaptive mutations. Overall, selective pressure on the NP gene of human influenza A viruses appeared to be dominated by purifying selection with a mean d N/d S ratio of 0.105. Site-selection analysis of 488 codons, however, also revealed 3 positively selected sites in addition to 139 negatively selected ones. Conclusions: The demographic history inferred by Bayesian skyline plot showed that the effective number of infections underwent a period of smooth and steady growth from 1998 to 2001, followed by a more recent rise in the rate of spread. Further understanding the correlates of interspecies transmission of influenza A virus genes from other host reservoirs to the human population may help to elucidate the mechanisms of variability among influenza A virus. © 2011 Lin et al. Source


Wu F.-T.,Center for Research and Diagnostics | Wu F.-T.,National Yang Ming University | Banyai K.,Veterinary Medical Research Institute | Huang J.C.,National Yang Ming University | And 10 more authors.
Clinical Microbiology and Infection | Year: 2011

Genotype P[25] rotaviruses are rare and to date have been reported to occur only in a few countries of mainland Asia. Here we report the molecular characterization of a novel human rotavirus genotype combination, G3P[25], detected in a 17-month-old child hospitalized due to severe gastroenteritis during 2009 in central Taiwan. Sequencing and phylogenetic analysis of the VP4 gene demonstrated a distinct origin from other strains bearing the P[25] VP4 gene, whereas the VP7, VP6 and NSP4 gene phylogenies identified common origins with cognate genes of other, presumed human-porcine reassortment Taiwanese strains. These results suggest that interactions between human and animal strains appear to contribute to the generation of genetic and antigenic diversity of rotavirus strains, with potential public health importance in Taiwan. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases. Source

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