Papers by Ching-chuan Liu
Vaccines, 2021
The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on overall community-acquired ... more The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on overall community-acquired pneumonia (CAP) and disease severity still needs thorough evaluation. In this study, we retrieve both pneumococcal CAP (P-CAP) and unspecific CAP (U-CAP) inpatient data from the Taiwan National Health Insurance Database (NHID) between 2005 and 2016. The interrupted time-series (ITS) analysis was performed to compare the incidence trend before and after the implementation of PCV13. After PCV13 implementation, there is a significant decreasing trend of P-CAP hospitalization, especially in children <1 year, 2–5 years, adults aged 19–65 years, 66 years, or older (all p value < 0.05). This corresponds to a 59% reduction in children <1 year, 47% in children aged 2–5 years, 39% in adult aged 19–65 years, and 41% in elderly aged 66 years or older. The intensive care rate (6.8% to 3.9%), severe pneumonia cases (21.7 to 14.5 episodes per 100,000 children–years), and the need for invasive ...
Journal of the Formosan Medical Association, 2015
Journal of the Formosan Medical Association, 2015
Genome announcements, 2013
Virus Research, 2008
Genetic recombination is a well-known phenomenon for enteroviruses. In this study, we determined ... more Genetic recombination is a well-known phenomenon for enteroviruses. In this study, we determined the phylogenetic relationships of five distinct regions of the EV71 genome for 73 EV71 isolates from 1986 and from 1998 to 2005 in Taiwan. Phylogenetic analyses showed that the 5-UTR, VP4-VP2, VP1, and 3D regions of EV71 isolated in 2004 and 2005 were grouped into genotype C. However, the 2B region of these isolates differed in that it grouped with genotype B, indicating recombination within EV71 had occurred. This intratypic recombination was first seen in 2002 and became predominant in 2004 and 2005. The simplot and bootscan analyses identified two recombination points located at the 3-termini of the 2A and 3C regions. This intratypic recombination was identified among naturally circulating EV71 isolates in Taiwan, therefore, it suggests that nonstructural genes may recombine to produce new EV71 variants.
Pharmacoepidemiology and Drug Safety, 2014
Microbial Pathogenesis, 2004
Previous studies show that isogenic mutants deficient in streptococcal pyrogenic exotoxin B (SPE ... more Previous studies show that isogenic mutants deficient in streptococcal pyrogenic exotoxin B (SPE B) cause less mortality and skin tissue damage than wild-type strains of Streptococcus pyogenes when inoculated into mice via an air pouch. In this study, the growth and dissemination of bacteria, pathologic changes in various organs, and their correlation with SPE B production were examined. Bacterial numbers in the air pouch from wild-type strain NZ131-infected mice increased at 48 h, while those from speB mutant SW510-infected mice continuously reduced. Mice infected with NZ131 developed bacteremia and greater dissemination in the kidney, liver, and spleen; those infected with SW510 showed either no or slight bacteremia and dissemination. Co-inoculation of SW510 with recombinant SPE B showed a higher bacterial count in the air pouch, bacteremia, and organ dissemination compared to co-inoculation with a C192S mutant lacking protease activity. The histopathologic changes examined showed lesions in kidney and liver in the NZ131-infected but not in SW510-infected mice. The elevation in sera of BUN, AST, and ALT correlated positively with renal and liver impairment. Taken together, SPE B produced during S. pyogenes infection plays a pathogenic role. A direct effect of SPE B on vessel permeability change was also demonstrated.
Journal of Virology, 2001
Avian coronavirus infectious bronchitis virus (IBV) is the causative agent of chicken infectious ... more Avian coronavirus infectious bronchitis virus (IBV) is the causative agent of chicken infectious bronchitis, an acute, highly contagious viral respiratory disease. Replication of IBV in Vero cells causes extensive cytopathic effects (CPE), leading to destruction of the entire monolayer and the death of infected cells. In this study, we investigated the cell death processes during acute IBV infection and the underlying mechanisms. The results show that both necrosis and apoptosis may contribute to the death of infected cells in lytic IBV infection. Caspase-dependent apoptosis, as characterized by chromosomal condensation, DNA fragmentation, caspase-3 activation, and poly(ADP-ribose) polymerase degradation, was detected in IBV-infected Vero cells. Addition of the general caspase inhibitor z-VAD-FMK to the culture media showed inhibition of the hallmarks of apoptosis and increase of the release of virus to the culture media at 16 h postinfection. However, neither the necrotic process n...
Journal of the Formosan Medical Association, 2012
Journal of Microbiology, Immunology and Infection, 2015
Background: Group A streptococcus (GAS) is a common pathogen in children. Macrolide resistance in... more Background: Group A streptococcus (GAS) is a common pathogen in children. Macrolide resistance in GAS has been described worldwide. The aims of this study are to analyze macrolide resistance of GAS isolates in southern Taiwan and to clarify the relationship of emm typing and macrolide resistance in the past decade. Methods: All GAS isolated from patients younger than 18 years at a single tertiary center in southern Taiwan were collected from 2000 to 2012. Antibiotics susceptibility to erythromycin, azithromycin, and clindamycin were determined by agar dilution method, and were interpreted by Clinical and Laboratory Standards Institute (CLSI) standards. emm typing was performed by polymerase chain reaction (PCR). Results: A total of 301 isolates were collected during the period of 13 years. Scarlet fever (38.5%) and acute pharyngitis (32.2%) were the most common diagnosis. Decreased resistance rate of erythromycin from 53.1% in 2000 to 0% in 2010 was found, but it increased rapidly to 65% in 2011. The resistance rate of azithromycin was the lowest (4.2%) in 2005, but was higher than 15% after 2006. The involvement of the erythromycin resistance genes were mefA (53.1%), ermB (35.9%), and ermTR (10.9%). The resistance of clindamycin also increased since
Journal of Medical Virology, 2001
Dengue virus infection causes a wide range of diseases from dengue fever to life-threatening deng... more Dengue virus infection causes a wide range of diseases from dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). The mechanisms involved in DHF/DSS pathogenesis remain unclear. Patient sera collected from an outbreak in southern Taiwan from November 1998 to January 1999 were studied. The presence of antibodies which cross-reacted with platelets could be detected in patient sera, and the isotype of these autoantibodies was IgM. The anti-platelet IgM levels were higher in DHF/DSS than in dengue fever patient sera in disease acute phase. These autoantibodies were still detectable in convalescent stage (1±3 weeks after acute phase) and even eight to nine months after illness. The platelet binding activity was not observed in other virusinfected patient sera tested. Further investigation showed that dengue patient sera caused platelet lysis in the presence of complement. The platelet cytotoxicity induced by DHF/DSS patient sera was higher than that by dengue fever sera. Dengue patient sera also inhibited platelet aggregation which, however, appeared to be not related to DHF/DSS development.
Journal of Hospital Infection, 2010
(NTUH) adopted international guidelines for surveillance and control of healthcare-associated inf... more (NTUH) adopted international guidelines for surveillance and control of healthcare-associated infection (HCAI) in 1981. This report describes the secular trends in HCAI at the NTUH over the past 27 years according to site of infection, aetiological agents and control measures. Clinical and microbiological data were collected by infection prevention and control nurses using a standardised case-record form. Specific control programmes were implemented and/or intensified as needed. Poisson or negative binomial regression analysis was used to quantify time trends of the incidence of HCAI. The annual number of discharges increased from 25 074 to 91 234 with a parallel increase in the Charlson comorbidity index. Active HCAI surveillance and periodic feedback were associated with a marked decrease in surgical site infections from 1981 to 2007 (2.5 vs 0.5 episodes per 100 procedures, P < 0.0001). On the other hand, there was a 4.8-fold increase in bloodstream infections (BSIs) (0.39 vs 1.88 episodes per 100 discharges, P < 0.0001). The average annual increase of pathogen-specific HCAI incidence during 1981e2007 was 11.4% for meticillin-resistant Staphylococcus aureus (MRSA), 75.4% for extensively drug-resistant A. baumannii (XDRAB), and 7.5% for Candida albicans (P < 0.0001, respectively). The infection prevention and control programme was upgraded in 2004 by implementing annual, intensive, project-based control programmes, and decreases in rates of HCAI, BSI, MRSA and XDRAB were observed. This long term study demonstrates the need to couple surveillance of HCAI with focused control programmes. Hospitals must invest in adequate manpower to accomplish these goals.
Journal of Clinical Virology, 2000
Background: In a recent enterovirus outbreak in Taiwan, serotype 71 was the culprit of encephalit... more Background: In a recent enterovirus outbreak in Taiwan, serotype 71 was the culprit of encephalitis causing rapid clinical deterioration and death among young children. Objecti6es: Since knowledge of enterovirus 71 (EV71) infection in the central nervous system is still limited, the purpose of the present case study was attempted to uncover the pathogenesis of the virus. Study design: We performed a detailed pathological examination, virological and molecular studies on a case of EV71 infection with a rapidly fatal outcome. In addition, the whole genome of the virus was sequenced to determine the genetic relationships to other enteroviruses and two other EV71 strains (a prototype BrCr and a neurovirulent MS strain), and to provide the genetic basis of its neurovirulence of the new isolate, NCKU9822 strain. Results: Characteristic features of acute encephalomyelitis were observed, with most prominent lesions in the spinal cord and brain stem. Mild myocarditis and pancreatitis were also noticed. EV71 antigen was localized to neurons on immunohistochemical staining. EV71 was recovered from all organs with inflammatory reaction. Sequence analysis showed that overall NCKU9822 and the two EV71 strains shared 80% nucleotide identity and 95% amino acid identity. It had only 45% amino acid and 52% nucleotide identities with polioviral P1 capsid region. Conclusion: The spinal cord and brain stem were the main targets of EV71 in the fatal cases in this outbreak, however, heart and pancreas might also be involved. Since the amino acid sequences in the P1 region are conserved (97% identity) among the three EV71 strains as compared to other enteroviruses and polioviruses, these EV71 neurovirulent
Journal of Clinical Virology, 2009
Background: In Taiwan, trivalent oral poliovirus vaccine (tOPV) is in the routine immunization sc... more Background: In Taiwan, trivalent oral poliovirus vaccine (tOPV) is in the routine immunization schedule, but its association with illnesses had not been examined. Objectives: To investigate clinical presentations and viral characteristics of patients with poliovirus isolates. Study design: Clinical data, vaccination records and viral sequences were retrospectively analyzed for patients from whom polioviruses were isolated during 2000-2005. Results: OPV-like strains were the only pathogen identified in 208 children who were diagnosed with lower respiratory tract infection (24.5%), acute gastroenteritis (16.8%) or upper respiratory tract infection (10.6%). Timing of poliovirus isolation relative to the tOPV vaccination was unusual in 59 patients, including 6 before any dose and 53 more than 10 weeks after the 3rd or later dose of tOPV. Sequence analyses of the VP1, 2C and 3C/D regions for 19 poliovirus isolates revealed that 4 had previously reported neurovirulence reversions, 1 had intertypic recombination, and 6 had both. No patient had neurological complications, but 3 died of myocarditis, including 2 with recombinant strains and 1 who never received OPV. Conclusion: This study describes the isolation of OPV-like strains from patients with a variety of illnesses, raising concerns about their pathogenic potential in an area where tOPV is routinely administered. The detection of genetic variations among OPV-like strains warrants continuing surveillance for these variants in patients with severe illnesses besides neurological complications.
Journal of Biological Chemistry, 2009
We have previously identified integrin ␣ v  3 and Fas as receptors for the streptococcal pyrogen... more We have previously identified integrin ␣ v  3 and Fas as receptors for the streptococcal pyrogenic exotoxin B (SPE B), and G308S, a mutant of SPE B that binds to Fas only. In the current study we found that after binding to ␣ v  3 , SPE B stimulated the tyrosine phosphorylation of JAK2 and STAT1. STAT1 tyrosine phosphorylation was inhibited by a JAK2 inhibitor, AG490, short interfering RNA (siRNA) silencing of JAK2, and anti-␣ V  3 antibody. AG490 also decreased the binding of tyrosine-phosphorylated STAT1 to the procaspase 8 promoter, decreasing procaspase 8 expression, suggesting that SPE B up-regulates procaspase 8 expression via the JAK2/STAT1 pathway. Alternatively, both SPE B and G308S increased STAT1 phosphorylation at serine 727, which was inhibited by anti-Fas antibody, a p38 inhibitor, SB203580, and siRNA silencing of p38. In addition, SPE B and G308S increased binding of serine-phosphorylated STAT1 to the Bax promoter and Bax expression, which was decreased by SB203580. SPE B and G308S-stimulated Bax expression was also inhibited by anti-Fas antibody. These findings suggest that Fas mediate SPE B-induced Bax expression through p38. Silencing of JAK2 or p38 by siRNA blocked procaspase 8 expression, whereas only p38 siRNA decreased Bax expression. Furthermore, JAK2 inhibition and p38 inhibition reduced SPE B-induced apoptosis, but only p38 inhibition blocked G308S-induced apoptosis. Streptococcus pyogenes (group A streptococcus) causes a wide spectrum of infection, including pharyngitis, cellulitis, and severe invasive diseases, such as necrotizing fasciitis and streptococcal toxic shock syndrome (1-3). Streptococcal pyrogenic exotoxin B (SPE B) 2 is secreted by all group A
International Journal of Medical Microbiology, 2010
Bacteria encounter oxidative stress by exposure to reactive oxygen species (ROS) present in the a... more Bacteria encounter oxidative stress by exposure to reactive oxygen species (ROS) present in the aerobic environment and during immune responses. In Streptococcus pyogenes, Dpr has been identified as a stress protein conferring resistance to hydrogen peroxide and multiple other stresses. The expression of Dpr is under perR (peroxide stress response regulator) control. However, the exact molecular mechanism of PerR regulation of Dpr is not clear. In this study, a perR deletion mutant was constructed by double cross-over mutagenesis. The profile of Dpr expression, performed by Western blot assay, revealed growth-phase dependency under normal culture conditions. Dpr expression decreased under iron-restricted conditions, whereas iron, zinc, nickel, and hydrogen peroxide induced its expression. The perR mutant does not induce Dpr as well when exposed to environmental signals. PerR binds the promoter region of dpr. Increased iron and hydrogen peroxide concentrations decreased PerR binding to the promoter region of dpr, suggesting that regulation of Dpr by environmental signals is mediated by PerR directly.
Cytokine, 2005
Recent work carried out in our laboratory showed the existence of a cytokine storm in SARS patien... more Recent work carried out in our laboratory showed the existence of a cytokine storm in SARS patients, dominated by Th1-type mediators. We thus hypothesized that IFN-g may play a major role in the pathology by triggering immune-mediated alveolar damage. As we assessed or reassessed some effects of IFN-g on a number of human lung epithelial and fibroblast cell lines, chosen for their wide use in the literature, we found that alveolar epithelial cells were more sensitive to IFN-g, in terms of proliferation inhibition and enhancement of Fas-mediated apoptosis. While similar effects were obtained on fibroblasts, concentrations of IFN-g 4e8-fold greater were required. In addition, both epithelial and fibroblastic cell lines were able to secrete large quantities of T celltargeting chemokines, similar to the ones detected in SARS patients. Based on the clinical data collected previously, the available literature and our in vitro experimentation, we propose that IFN-g may be responsible for acute lung injury in the late phase of the SARS pathology.
Clinical Infectious Diseases, 2006
Background. This study was designed to compare the clinical characteristics, toxin expression, vi... more Background. This study was designed to compare the clinical characteristics, toxin expression, virulence factors, and antimicrobial susceptibilities of staphylococci isolated from Taiwanese children with staphylococcal toxic shock syndrome (STSS) and staphylococcal scalded skin syndrome (SSSS). Methods. Demographic characteristics, hospital course, and outcomes of the children were analyzed. Toxinspecific and virulence genes of the staphylococci were detected by polymerase chain reaction amplification. Antimicrobial susceptibilities were determined by disk diffusion and the Etest. Results. Staphylococcus aureus was isolated from 16 children (6 in the STSS group and 10 in the SSSS group). Children with STSS tended to be older than those with SSSS, had a longer duration of hospitalization, and a much higher mortality rate. Community-associated methicillin-resistant S. aureus was isolated from 11 (68.8%) of 16 children. All of these isolates contained the ermB and mecA genes, but none had the mefA gene. All 16 isolates tested positive for the fnbA gene. The pvl and seb genes were more frequently found among S. aureus from the STSS group, compared with S. aureus from the SSSS group. We found that 67% (4 of 6) of the STSS isolates were genetically related. All of the S. aureus isolates were susceptible to vancomycin, gentamicin, doxycycline, and trimethoprim-sulfamethoxazole. Most isolates were resistant to clindamycin (63%), oxacillin (69%), and clarithromycin (81%). Conclusions. The most distinguishing feature of these isolates is the greater frequency of pvl and seb carriage among those from the STSS group. Most of the isolates were community-associated methicillin-resistant S. aureus that were highly resistant to macrolides but susceptible to trimethoprim-sulfamethoxazole. Vancomycin remains the initial drug of choice for treatment of STSS and SSSS. More studies are needed to determine the efficacy of trimethoprim-sulfamethoxazole in children with these syndromes.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi, 2007
Group D non-typhoidal Salmonella infection is increasing in Taiwan. This study aimed to investiga... more Group D non-typhoidal Salmonella infection is increasing in Taiwan. This study aimed to investigate the changing serotypes and antibiotic resistance of childhood group D Salmonella infection. From 1998 through 2004, children (<16 years) infected with group D Salmonella were retrospectively reviewed. Demographic data, clinical and laboratory features, and risk factors of bacteremia were analyzed. Enrolled patients were classified as acute gastroenteritis with bacteremia (Group I) and acute gastroenteritis without bacteremia (Group II). The minimal inhibitory concentrations were determined by agar dilution method. Genotyping was performed by use of pulsed-field gel electrophoresis (PFGE). Eighty one children (Group I, n = 15; Group II, n = 66) were enrolled with a mean (+/- standard deviation) age of 3.1 +/- 2.6 years. Group I patients were younger and had a longer duration of fever prior to admission (> or =5 days, 40% vs 9.2%; p=0.003) and total fever duration (8.3 vs 4.1 days...
Emerging Infectious Diseases, Mar 1, 2004
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Papers by Ching-chuan Liu