Browsing by Author "Chen, Yen-Hsu"

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AIDS-related opportunistic illnesses and early initiation of HIV care remain critical in the contemporary HAART era: a retrospective cohort study in Taiwan
(2018-07-28)
Lee, Chun-Yuan
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Tseng, Yu-Ting
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Lin, Wei-Ru
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Chen, Yen-Hsu
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Tsai, Jih-Jin
Background: No study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART). Methods: Eligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010-2011, 2012-2013, and 2014-2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality. Results: Over a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/mu L experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOls (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of < 200 cells/mu L at presentation was associated with increased adjusted odds of an AOI within 90 days [adjusted odds ratio, 40.84; 95% confidence intervals (CI), 12. 59-132.49] and an elevated adjusted hazard of all-cause mortality (adjusted hazard ratio, 11.03; 95% CI, 1.51-80.64). Conclusions: Despite efforts toward HIV prevention and management, early HIV care in Taiwan continues to be critically affected by AOI-related morbidity and mortality in the era of contemporary HAART. Additional targeted interventions are required for the earlier diagnosis of patients with HIV.
Are we ready for the global emergence of multidrug-resistant Candida auris in Taiwan?
(2018-06-01)
Lu, Po-Liang
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Liu, Wei-Lun
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Lo, Hsiu-Jung
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Wang, Fu-Der
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Ko, Wen-Chien
Candida auris is a recently identified multi-resistant Candida species, first reported in Japan in 2009, and poses a serious global health threat. Lack of awareness of this new Candida species and difficulties with laboratory identification have impacted significantly on outbreak detection and management, and compromised patient outcome. Accordingly, there is an urgent need to raise awareness of healthcare personnel to this emerging pathogen and determine its prevalence, impact, and challenges to the Taiwan healthcare system. Enhanced laboratory testing strategies are needed to differentiate C. auris from other Candida species to provide accurate diagnosis and implement control measures early enough to prevent hospital outbreaks. In this report, we review the key epidemiological, microbiological and clinical characteristics of C. auris and provide the results of a multicenter surveillance study of C. auris in Taiwan. We also conducted a web-based survey to determine awareness of the medical community to C. auris and the capability of Taiwanese hospital laboratories to identify this microorganism. C. auris has not yet been isolated from humans in Taiwan, but the unique features of this microorganism and its ability to reach across international boundaries justify the importance of these initiatives in Taiwan.(C) 2017, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license.
Association between neighborhood greenspace and fasting plasma glucose from a large cohort study in Taiwan
(2019-08-01)
Lin, Bo-Cheng
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Yen, Yun-Ting
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Lan, Xiang Qian
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Chen, Yen-Hsu
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Chan, Ta-Chien
Growing evidence suggests that greenness exposure improves health status, but few studies address diabetes, and research mainly comes from Western countries. This study hypothesizes that higher greenness exposure benefits glucose control with increased intensity of physical activity. We used data from a longitudinal health examination database in Taiwan during 2000-2014. The normalized difference vegetation index (NDVI) was used as an objective indicator of greenness in the neighborhood. Fasting plasma glucose served as an indicator of early diabetes diagnosis. A metabolic equivalent value (MET) based on a compendium of physical activities was used to estimate the intensity of physical activity. We applied a linear mixed-effect model with an individual-level random effect to investigate the relationship between neighborhood greenness and the fasting plasma glucose value stratified by four levels of physical activity. There are 341,211 participants with no diabetes, and 773,602 check-up visits included here. The fasting glucose among participants living in areas with higher green space was lower than that of those living in less green areas. The beneficial effects of greenspace on glucose were stronger for those with more physical activity, especially in the 500-m buffer. In the physically inactive group, compared with the lowest quantile (Q1) of cumulative average greenness, people living in the highest quantile (Q4) of greenness had 0.35 mg less glucose in each dl of plasma [95% confidence interval: -0.50, - 0.20]. In the physically active group, people residing in the highest quantile (Q4) of greenness had 0.48 mg less glucose in each dl of plasma [95% confidence interval: -0.73, -0.23]. Higher residential greenness appears to be associated with lower glucose. Higher physical activity can mediate this association. Our results provide evidence that ensuring access to greenspace in residential neighborhoods may provide positive health outcomes and improve public health, and should be implemented in urban planning.
Association of Human Q Fever with Animal Husbandry, Taiwan, 2004-2012
(2015-12-01)
Lai, Chung-Hsu
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Chang, Lin-Li
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Lin, Jiun-Nong
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Liao, Ming-Huei
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Liu, Shyh-Shyan
In Taiwan, Q fever cases in humans began increasing in 2004 and peaked in 2007 but dramatically declined in 2008 and 2011. Cases were significantly correlated with the number of goats. The decline might be associated with the collateral effects of measures to control goat pox in 2008 and 2010.
Capnocytophaga sputigena pneumonia and bacteremia in a patient with diabetes and gastric cancer
(2018-08-01)
Lo, Shih-Hao
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Chang, Yung-Yun
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Jao, Ya-Ting
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Wang, Wen-Hung
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Lu, Po-Liang
Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity
(2019-02-01)
Chang, Ko
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Lee, Nan-Yao
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Ko, Wen-Chien
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Lin, Wei-Ru
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Chen, Yen-Hsu
Background/purpose: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. Methods: We conducted a retrospective study to identify the characteristics of the elderly aged >= 65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011. Results: Among 441 cases, including 187 cases of scrub typhus, 166 acute Qfever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99). Conclusion: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications. Copyright (C) 2017, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.
Characterization of the Drug Resistance Profiles of Patients Infected with CRF07_BC Using Phenotypic Assay and Ultra-Deep Pyrosequencing
(2017-01-20)
Huang, Szu-Wei
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Li, Wei-You
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Wang, Wen-Hung
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Lin, Yu-Ting
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Chou, Chih-Hung
The usefulness of ultra-deep pyrosequencing (UDPS) for the diagnosis of HIV-1 drug resistance (DR) remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004 - 2005) and 3 from late epidemic (collected in 2008) were obtained from treatment-naive patient\'s peripheral blood mononuclear cells. Viral RNA was extracted directly from patient\'s plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay) and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs) (4.4 - 47.3 fold). Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01 +/- 0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.
Cyclooxygenase-2 facilitates dengue virus replication and serves as a potential target for developing antiviral agents
(2017-03-20)
Lin, Chun-Kuang
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Tseng, Chin-Kai
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Wu, Yu-Hsuan
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Liaw, Chih-Chuang
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Lin, Chun-Yu
Cyclooxygenase-2 (COX-2) is one of the important mediators of inflammation in response to viral infection, and it contributes to viral replication, for example, cytomegalovirus or hepatitis C virus replication. The role of COX-2 in dengue virus (DENV) replication remains unclear. In the present study, we observed an increased level of COX-2 in patients with dengue fever compared with healthy donors. Consistent with the clinical data, an elevated level of COX-2 expression was also observed in DENV-infected ICR suckling mice. Using cell-based experiments, we revealed that DENV-2 infection significantly induced COX-2 expression and prostaglandin E-2 (PGE(2)) production in human hepatoma Huh-7 cells. The exogenous expression of COX-2 or PGE2 treatment dose-dependently enhanced DENV-2 replication. In contrast, COX-2 gene silencing and catalytic inhibition sufficiently suppressed DENV-2 replication. In an ICR suckling mouse model, we identified that the COX-2 inhibitor NS398 protected mice from succumbing to life-threatening DENV-2 infection. By using COX-2 promoter-based analysis and specific inhibitors against signaling molecules, we identified that NF-kappa B and MAPK/JNK are critical factors for DENV-2-induced COX-2 expression and viral replication. Altogether, our results reveal that COX-2 is an important factor for DENV replication and can serve as a potential target for developing therapeutic agents against DENV infection.
Decline in invasive pneumococcus diseases while combating the COVID-19 pandemic in Taiwan
(1970-01-01)
Tsai, Jong-Rung
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Yang, Chih-Jen
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Huang, Wei-Ling
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Chen, Yen-Hsu
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生物科技學系
Development of an Animal Model for Alcoholic Liver Disease in Zebrafish
(2015-08-01)
Lin, Jiun-Nong
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Chang, Lin-Li
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Lai, Chung-Hsu
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Lin, Kai-Jen
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Lin, Mei-Fang
Alcoholic liver disease (ALD) continues to be a major cause of liver-related morbidity and mortality worldwide. To date, no zebrafish animal model has demonstrated the characteristic manifestations of ALD in the setting of chronic alcohol exposure. The aim of this study was to develop a zebrafish animal model for ALD. Male adult zebrafish were housed in a 1% (v/v) ethanol solution up to 3 months. A histopathological study showed the characteristic features of alcoholic liver steatosis and steatohepatitis in the early stages of alcohol exposure, including fat droplet accumulation, ballooning degeneration of the hepatocytes, and Mallory body formation. As the exposure time increased, collagen deposition in the extracellular matrix was observed by Sirius red staining and immunofluorescence staining. Finally, anaplastic hepatocytes with pleomorphic nuclei were arranged in trabecular patterns and formed nodules in the zebrafish liver. Over the time course of 1% ethanol exposure, upregulations of lipogenesis, fibrosis, and tumor-related genes were also revealed by semiquantitative and quantitative real-time reverse transcription-polymerase chain reaction. As these data reflect characteristic liver damage by alcohol in humans, this zebrafish animal model may serve as a powerful tool to study the pathogenesis and treatment of ALD and its related disorders in humans.
Differences in Mortality and Clinical Manifestations of Dengue Hemorrhagic Fever in Taiwan in Different Years: A Comparison for Cases in 2014 and 2015 Epidemics
(2017-01-01)
Chang, Ko
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Huang, Chung-Hao
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Lee, Ing-Kit
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Lu, Po-Liang
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Lin, Chun-Yu
People in southern Taiwan experienced two major dengue outbreaks in 2014 and 2015. The mortality and clinical features were very different between these 2 years. Dengue virus serotype 1 (DENV-1) caused epidemic outbreak in 2014 and DENV-2 was predominant in 2015. The characteristics of dengue hemorrhagic fever (DHF) cases in the 2 years was analyzed. We conducted a retrospective chart review to analyze the clinical and laboratory features of 206 adult patients with DHF in southern Taiwan in 2014 and 2015. The mortality rate of DHF cases in 2015 was higher than that of cases in 2014 (38.7% versus 12.4%, P < 0.0001). Compared with cases in 2014, DHF cases in 2015 had more complications, such as gastrointestinal bleeding (78.5% versus 61.9%, P = 0.01), severe hepatitis (30.1% versus 8%, P < 0.0001), and myocarditis (14% versus 0.9%, P < 0.0001). Among the mortality cases, diabetes, chronic renal failure, proton-pump inhibitors using, platelet transfusion, and Charlson comorbidity index score (Charlson score) were also higher in 2015. Multivariate analysis for the mortality cases revealed that the risk factors were Charlson score (3) 5 (P = 0.02, odds ratio [OR] = 4.07, 95% confidence interval [CI] = 1.244-13.307), severe hepatitis (P < 0.0001, OR = 11.97, 95% CI = 3.831-37.396), and acute renal failure (P < 0.0001, OR = 98.76, 95% CI = 10.847-899.22). DHF cases in 2015 had higher mortality and more complications, such as gastrointestinal bleeding, severe hepatitis, and myocarditis, than in 2014 in southern Taiwan. In the 2-year DHF case series, Charlson score >= 5, severe hepatitis, and acute renal failure were independent significant variables for mortality.
Effects of various antimicrobial stewardship programs on antimicrobial usage and resistance among common gram-negative bacilli causing health care-associated infections: A multicenter comparison
(2016-02)
Lai, Chung-Chih
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Shi, Zhi-Yuan
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Chen, Yen-Hsu
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Wang, Fu-Der
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生醫工程研究所
Background: The effects of various antimicrobial stewardship programs (ASPs) on both antibiotic consumption and resistance among different hospitals within the same insurance system have rarely been investigated. Methods: This 6-year retrospective study included three medical centers with similar facilities and infection control measures in Taiwan. These hospitals used different types of ASPs: one had a hospital-wide preauthorization requirement by infectious diseases physicians for all broad-spectrum antibiotics, covering all intensive care units; the second used the program, but excluded all intensive care units; and the third used postprescription review only. The nonsusceptibility of unduplicated isolates of gram-negative bacilli causing health care associated infections and consumption of broad-spectrum antibiotics were analyzed. Results: Overall, the usage of broad-spectrum antibiotics of all classes escalated significantly over time in all three hospitals, but consumption was lowest under the hospital-wide pre authorization program. Under this ASP, despite a 2-fold increase in the total broad-spectrum antibiotic consumption during study period, some declining trends of resistance were found, including ciprofloxacin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and carbapenem-resistant P. aeruginosa. By contrast, the other two hospitals with preauthorization program excluding all intensive care units and postprescription review had similar high broad-spectrum antibiotic consumption, comparable growing trends of resistant strains in general, and the correlations of antibiotic consumption and resistance were basically positive. Carbapenem-resistant A. baumannii increased significantly over time in all three hospitals. Conclusion: This interhospital comparison suggested that hospital-wide preauthorization program is the most effective to reduce key gram-negative bacilli resistance, with the exception of carbapenem-resistant A. baumannii. Copyright (C) 2015, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EGFR Tyrosine Kinase Inhibitor-Associated Interstitial Lung Disease During the Coronavirus Disease 2019 Pandemic
(2020-08-01)
Chang, Hsu-Liang
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Chen, Yen-Hsu
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Taiwan, Hsin-Chu
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Yang, Chih-Jen
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生醫工程研究所
Epidemiology and antifungal susceptibility of candidemia isolates of non-albicans Candida species from cancer patients
(2017-10-11)
Wu, Ping-Feng
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Liu, Wei-Lun
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Hsieh, Min-Han
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Hii, Ing-Moi
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Lee, Yu-Lin
Candidemia is a growing concern worldwide, and its species distribution has shifted toward non-albicans Candida in recent decades, especially in patients with malignancy. This study aimed to update the epidemiology and antifungal susceptibility of non-albicans candidemia isolates from the cancer patients. Adult cancer patients with non-albicans candidemia were recruited, and clinical data were retrospectively collected from five medical centers in Taiwan from 1 July 2011 to 30 June 2014. In vitro susceptibility was determined by the broth dilution method using a Sensititre YeastOne system and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 346 episodes of non-albicans candidemia were identified in cancer patients. Candida tropicalis was the most common species (n=145, 41.9%) and had the highest resistance rate to fluconazole (n=17, 13.9%) among all the preserved isolates, including C. tropicalis, Candida glabrata and Candida parapsilosis. A higher Charlson comorbidity index, non-albicans candidemia due to C. tropicalis, neutropenia and septic shock were independent predictors of 28-day mortality. In conclusion, the species distribution and antifungal susceptibility of non-albicans candidemia isolates in our study differed from those in Western countries, providing useful information about local epidemiology for the selection of empirical antifungal agents for cancer patients.
Epidemiology and trends in the antibiotic susceptibilities of Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region, 2010-2013
(2017-06-01)
Chang, Ya-Ting
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Coombs, Geoffrey
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Ling, Thomas
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Balaji, V.
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Rodrigues, Camilla
This study was conducted to investigate the epidemiology and antimicrobial susceptibility patterns of Gram-negative bacilli (GNB) isolated from intra-abdominal infections (IAIs) in the Asia-Pacific region (APR) from 2010-2013. A total of 17 350 isolates were collected from 54 centres in 13 countries in the APR. The three most commonly isolated GNB were Escherichia coli (46.1%), Klebsiella pneumoniae (19.3%) and Pseudomonas aeruginosa (9.8%). Overall, the rates of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae were 38.2% and 24.3%, respectively, and they were highest in China (66.6% and 38.7%, respectively), Thailand (49.8% and 36.5%, respectively) and Vietnam (47.9% and 30.4%, respectively). During 2010-2013, the rates of ESBL-producing E. coli and K. pneumoniae isolates causing community-associated (CA) IAIs (collected <48 h after admission) were 26.0% and 13.5%, respectively, and those causing hospital-associated (HA) IAIs were 48.0% and 30.6%, respectively. Amikacin, ertapenem and imipenem were the most effective agents against ESBL-producing isolates. Piperacillin/tazobactam displayed good in vitro activity (91.4%) against CA ESBL-producing E. coli. For other commonly isolated Enterobacteriaceae, fluoroquinolones, cefepime and carbapenems exhibited better in vitro activities than third-generation cephalosporins. Amikacin possessed high in vitro activity against all GNB isolates (>80%) causing IAIs, except for Acinetobacter calcoaceticus-baumannii (ACB) complex (30.9% for HA-IAI isolates). All of the antimicrobial agents tested exhibited <45% in vitro activity against ACB complex. Antimicrobial resistance is a persistent threat in the APR and continuous monitoring of evolutionary trends in the susceptibility patterns of GNB causing IAIs in this region is mandatory. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury
(2019-04-04)
Lee, Yi-Chen
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Lin, Chun-Yu
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Chen, Yen-Hsu
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Chiu, Wen-Chin
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Wang, Yen-Yun
Acute lung injury (ALI) is a life-threatening syndrome characterized by acute and severe hypoxemic respiratory failure. Visfatin, which is known as an obesity-related cytokine with pro-inflammatory activities, plays a role in regulation of inflammatory cytokines. The mechanisms of ALI remain unclear in critically ill patients. Survival in ALI patients appear to be influenced by the stress generated by mechanical ventilation and by ALI-associated factors that initiate the inflammatory response. The objective for this study was to understand the mechanisms of how visfatin regulates inflammatory cytokines and promotes ALI. The expression of visfatin was evaluated in ALI patients and mouse sepsis models. Moreover, the underlying mechanisms were investigated using human bronchial epithelial cell lines, BEAS-2B and NL-20. An increase of serum visfatin was discovered in ALI patients compared to normal controls. Results from hematoxylin and eosin (H&E) and immunohistochemistry staining also showed that visfatin protein was upregulated in mouse sepsis models. Moreover, lipopolysaccharide (LPS) induced visfatin expression, activated the STAT3/NF kappa B pathway, and increased the expression of pro-inflammatory cytokines, including IL1-beta, IL-6, and TNF-alpha in human bronchial epithelial cell lines NL-20 and BEAS-2B. Co-treatment of visfatin inhibitor FK866 reversed the activation of the STAT3/NF kappa B pathway and the increase of pro-inflammatory cytokines induced by LPS. Our study provides new evidence for the involvement of visfatin and down-stream events in acute lung injury. Further studies are required to confirm whether the anti-visfatin approaches can improve ALI patient survival by alleviating the pro-inflammatory process.
Establishment and Comparison of Two Different Diagnostic Platforms for Detection of DENV1 NS1 Protein
(2015-11-01)
Tang, Yin-Liang
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Chiu, Chien-Yu
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Lin, Chun-Yu
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Huang, Chung-Hao
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Chen, Yen-Hsu
Dengue virus (DENV) infection is currently at pandemic levels, with populations in tropical and subtropical regions at greatest risk of infection. Early diagnosis and management remain the cornerstone for good clinical outcomes, thus efficient and accurate diagnostic technology in the early stage of the disease is urgently needed. Serotype-specific monoclonal antibodies (mAbs) against the DENV1 nonstructural protein 1 (NS1), DA12-4, DA13-2, and DA15-3, which were recently generated using the hybridoma technique, are suitable for use in diagnostic platforms. Immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis further confirmed the serotype specificity of these three monoclonal antibodies. The ELISA-based diagnostic platform was established using the combination of two highly sensitive mAbs (DA15-3 and DB20-6). The same combination was also used for the flow cytometry-based diagnostic platform. We report here the detection limits of flow cytometry-based and ELISA-based diagnostic platforms using these mAbs to be 0.1 and 1 ng/mL, respectively. The collected clinical patient serum samples were also assayed by these two serotyping diagnostic platforms. The sensitivity and specificity for detecting NS1 protein of DENV1 are 90% and 96%, respectively. The accuracy of our platform for testing clinical samples is more advanced than that of the two commercial NS1 diagnostic platforms. In conclusion, our platforms are suitable for the early detection of NS1 protein in DENV1 infected patients.
Generation and Characterization of Antinonstructural Protein 1 Monoclonal Antibodies and Development of Diagnostics for Dengue Virus Serotype 2
(2017-01-01)
Tang, Yin-Liang
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Liu, I-Ju
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Li, Pi-Chun
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Chiu, Chien-Yu
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Lin, Chun-Yu
Dengue virus (DENV) circulates in tropical and subtropical areas around the world, where it causes high morbidity and mortality. There is no effective treatment of infection, with supportive care being the only option. Furthermore, early detection and diagnosis are important to facilitate clinical decisions. In this study, seven monoclonal antibodies (mAbs) recognizing nonstructural protein 1 (NS1) of DENV were generated by hybridoma techniques. These antibodies can be divided into two groups: serotype-specific (DB6-1, DB12-3, and DB38-1) and nonspecific (consisting of antibodies DB16-1, DB20-6, DB29-1, and DB41-2). The B-cell epitopes of DB20-6 and DB29-1 were identified by phage display and site-directed mutagenesis, and its binding motif, WXXWGK, was revealed to correspond to amino acid residues 115-120 of the DENV-2 NS1 protein. A diagnostic platform, consisting of a serotype-specific capture antibody and a complex detection antibody, exhibited a detection limit of about 1 ng/mL, which is sufficient to detect NS1 in clinical serum samples from dengue patients. This diagnostic platform displayed better specificity and sensitivity than two examined commercial NS1 diagnostic platforms. In summary, our results indicate that these newly generated mAbs are suitable for detection of NS1 protein of DENV-2 in clinical samples.
Google Trends-based non-English language query data and epidemic diseases: a cross-sectional study of the popular search behaviour in Taiwan
(2020-01-01)
Chang, Yu-Wei
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Chiang, Wei-Lun
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Wang, Wen-Hung
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Lin, Chun-Yu
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Hung, Ling-Chien
Objective This study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes. Design Cross-sectional study. Setting Freely available epidemic data in Taiwan. Main outcome measure We used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan. Results With our approach, we noted that keywords (sic)& x5192; ('common cold'), & x767c;& x71d2; ('fever') and & x54b3;& x55fd; ('cough') exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, p<0.001; r=0.773, p<0.001; r=0.796, p<0.001, respectively). They also displayed high correlation with influenza-like illness emergencies (r=0.900, p<0.001; r=0.802, p<0.001; r=0.886, p<0.001, respectively) and outpatient visits (r=0.889, p<0.001; r=0.791, p<0.001; r=0.870, p<0.001, respectively). We noted that the query & x8178;(sic)& x6bd2; ('enterovirus') exhibited excellent correlation with the number of enterovirus-infected patients in emergency departments (r=0.914, p<0.001). Conclusions These results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting.
HCV NS5A Up-Regulates COX-2 Expression via IL-8-Mediated Activation of the ERK/JNK MAPK Pathway
(2015-07-31)
Chen, Wei-Chun
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Tseng, Chin-Kai
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Chen, Yen-Hsu
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Lin, Chun-Kuang
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Hsu, Shihhsien
Chronic hepatitis C virus (HCV) infection leads to intrahepatic inflammation and liver cell injury, which are considered a risk factor for virus-associated hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. Inflammatory cytokines are critical components of the immune system and influence cellular signaling, and genetic imbalances. In this study, we found that cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) were significantly induced by HCV infection and HCV NS5A expression, and induction of COX-2 correlated with HCV-induced IL-8 production. We also found that the ERK and JNK signaling pathways were involved in the regulation of IL-8-mediated COX-2 induction in response to HCV infection. Using a promoter-linked reporter assay, we identified that the C/EBP regulatory element within the COX-2 promoter was the dominant factor responsible for the induction of COX-2 by HCV. Silencing C/EBP attenuated HCV-induced COX-2 expression. Our results revealed that HCV-induced inflammation promotes viral replication, providing new insights into the involvement of IL-8-mediated COX-2 induction in HCV replication.