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Background: The geographic distribution of the major clone of sequence type 131 (ST131) in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) infections is not known. We analyzed the clinical features, resistance mechanisms, and geographic distribution of ESBL-producing E. coli clones in 120 children. Methods: We studied the 120 ESBL-producing E. coli strains from children younger than 18 years. A VITEK 2 automated system was used to determine bacterial identification and ESBL production. Sequence type was determined by multi-locus sequence typing (MLST). The genetic relationship of the ESBL-producing strains was studied using pulsed-field gel electrophoresis (PFGE). Phylogenetic group and blaCTX-M group was performed using polymerase chain reaction (PCR). Multiplex PCR for detecting the common group 9 variant, CTX-M-14, and group 1 variant, CTX-M-15, was also performed. The addresses of the 120 children were collected, and plotted on the Taiwan map. Results: The groups in the center of Kaohsiung City lived mainly in urban areas with a population density of over 10,000 people per square kilometer, and the majority of the Kaohsiung groups on the outskirts of the city center lived in suburban areas with a population density of under 6000 people per square kilometer. There was no statistically significant difference between the city center and outskirt groups in terms of clinical presentation, laboratory, and imaging data. However, more ST131 clones, major pulsotype groups, and phylogenetic group B2 strains were found in the center of Kaohsiung than on the outskirts. Conclusion: ESBL-producing E. coli clones may be more challenging to treat clinically. Most infections were community-acquired, and there appeared to be major pulsotype clones, mainly in urban areas. This reinforces the necessity of environmental surveillance and sanitary procedures for ESBL-producing E. coli.

Background: The rapidly increasing prevalence of antimicrobial-resistant Escherichia coli (E. coli) is a global concern. This study determined the prevalence and risk factors for the fecal carriage of drug-resistant E. coli and extraintestinal pathogenic E. coli (ExPEC) among children. Materials and methods: In this prospective study, stool samples from children aged 0–18 years were obtained within three days of hospitalization between April 2016 and March 2019. E. coli were selected and tested for extended-spectrum β-lactamase (ESBL)-production and antimicrobial susceptibility. Multilocus sequence typing, blaCTX-M gene groups and ExPEC were determined using polymerase chain reactions. Questionnaires were recorded for risk factor analysis. Results: Among 179 E. coli isolates, 44.1% were multi-drug resistant, 20.7% produced ESBL, and 50.3% were ExPEC. Children carrying ESBL-producing E. coli were younger than those carrying non-ESBL strains. Several anthropogenic factors, including drinking water process, pork consumption, pets and household density might be associated with ESBL-producing E. coli, sequence type (ST) 131 E. coli, or ExPEC fecal carriage. Compared with families who live in less crowded houses, participants with pets had a similar trend of higher risks of ESBL-producing E. coli, ST131 E. coli, and ExPEC fecal carriage among those living in houses accommodating relatively more people. Conclusions: Children accounted for a large proportion of instances of feces carrying ESBL E. coli. In addition to antimicrobial control for people and livestocks, avenues of exposure, such as drinking water, food, pets, household density, and socioeconomic deprivation might present potentially novel opportunities to reduce the burden of nonsusceptible E. coli and ExPEC.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) strains hold the responsibility for the majority of E. coli infections. Numerous extraintestinal virulence factors (VFs) were possessed by ExPEC which are involved in the pathogenesis of infection. However, the effect of comorbidities or infection syndrome in the association of VFs and mortality remains inconclusive. Method: This study addressed whether specific sequence type (ST) and VFs of extended-spectrum beta-lactamase–producing E. coli (ESBL-EC) are associated with different outcomes in patients with bloodstream infection. 121 adults from southern Taiwan with ESBL-EC bloodstream infections were enrolled during a 6-year period. Demographic data, including infection syndromes, underlying disease and outcomes, were collected. The virulence factors in isolates were analyzed by PCR and multilocus sequence typing analyses were also performed. Result: Positivity for the virulence genes iha, hlyD, sat, iutA, fyuA, malX, ompT, and traT was associated with ST131 positivity (P

Abstract Background A severe dengue epidemic occurred in 2015 which resulted in over 22,000 laboratory-confirmed cases. A cross-sectional seroprevalence study was conducted during the ending phase of this epidemic to evaluate the true incidence of dengue virus (DENV) infection and the level of herd immunity. Methods Adult residents in three administrative districts with high dengue incidence were recruited; workers in two districts with intermediate dengue incidence were also recruited for comparison. DENV-specific IgM and IgG were tested using commercial enzyme-linked immunosorbent assays. DENV RNA was detected using commercial quantitative real-time reverse transcriptase polymerase chain reaction assay. Univariate and multivariate logistic regressions were performed to identify risk factors for recent and past DENV infection. Results The overall seroprevalence of anti-DENV IgM and IgG in 1391 participants was 6.8 and 17.4%, respectively. The risk of recent DENV infection increased with age, with the elderly having the highest risk of infection. Living in areas with high incidence of reported dengue cases and having family members being diagnosed with dengue in 2015 were also independent risk factors for recent DENV infection. One sample was found to have asymptomatic viremia with viral load as high as 105 PFU/ml. Conclusions Comparing the seroprevalence of anti-DENV IgM with the incidence of reported dengue cases in 2015, we estimated that 1 out of 3.7 dengue infections were reported to the surveillance system; widespread use of rapid diagnostic tests might contribute to this high reporting rate. The results also indicate that the overall herd immunity remains low and the current approved Dengvaxia® is not quite suitable for vaccination in Taiwan.

Abstract Background Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported. Methods We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel. Results Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7–446.9) by SD ELISA, while at 175.7 days (95% CI 121.9–221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively. Conclusion Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year.

Abstract Background The role of interleukin (IL) 17A in chronic liver diseases had been extensively studied, but the function of IL-17F, which shares a high degree of homology with IL-17A, in the progression of chronic hepatic diseases is poorly understood. The aim of the study was to evaluate the association between IL-17F and liver diseases including, fibrosis and hepatocellular carcinoma (HCC). Methods Hepatic tumor samples from both hepatitis C virus (HCV) positive and negative patients (without HBV and HCV, NBNC) were examined with quantitative PCR and immunohistochemistry staining for inflammatory cytokine genes expression. In addition, 250 HCV patients naïve for interferon treatment were also subjected to enzyme-linked immunosorbent Assay (ELISA) for their serum cytokine concentrations. Results Serum IL-17F concentrations were significantly elevated in HCV patients with severe fibrosis stages. In accordance with serum data, IL-17F expression was also found higher in HCV-associated HCC tissues compared with NBNC HCC tissues at both the mRNA and protein levels. Conclusions Our data suggest that IL-17F might be used as a valuable biological marker than IL-17A during chronic fibrosis progression and HCC development in HCV patients.

Background: This study aimed to investigate the frequency of sequence type (ST) 131 strains and outcome of cirrhotic patients with bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase-producing Escherichiacoli (ESBLEC) and non-extended-spectrum beta-lactamase-producing Escherichiacoli (NESBLEC). Methods: The incidence of ST 131 strains, hospital stay, and 30-day re-admission/mortality were compared between 51 ESBLEC and 51 NESBLEC bacteremic patients with cirrhosis. Results: ST 131 strains were found in 35.3% of the ESBLEC group and 0% of the NESBLEC group (p < 0.001). Mean hospital stay was 26.5 days in the ESBLEC group and 17.1 days in the NESBLEC group (p = 0.006). Thirty-day re-admission rates were 11.8% in the ESBLEC group and 5.9% in the NESBLEC group (p = 0.5). ST 131 strains were associated with 30-day re-admission (odds ratio: 4.5, 95% confidence interval: 1.1–18.9). Thirty-day mortality rate was 31.4% in the ESBLEC group and 23.5% in the NESBLEC group (p = 0.4). Conclusion: In patients with cirrhosis, the ESBLEC BSIs group had a higher frequency of ST 131 strains and longer hospital stay than the NESBLEC BSIs group with similar 30-day re-admission/mortality. ST 131 strains were associated with 30-day re-admission.

Zika virus (ZIKV) is primarily transmitted by Aedes mosquitoes in the subgenus Stegomyia but can also be transmitted sexually and vertically in humans. STAT1 is an important downstream factor that mediates type I and II interferon signaling. In the current study, we showed that mice with STAT1 knockout (Stat1-/-) were highly susceptible to ZIKV infection. As low as 5 plaque-forming units of ZIKV could cause viremia and death in Stat1-/- mice. ZIKV replication was initially detected in the spleen but subsequently spread to the brain with concomitant reduction of the virus in the spleen in the infected mice. Furthermore, ZIKV could be transmitted from mosquitoes to Stat1-/- mice back to mosquitoes and then to naïve Stat1-/- mice. The 50% mosquito infectious dose of viremic Stat1-/- mouse blood was close to 810 focus-forming units (ffu)/ml. Our further studies indicated that the activation of macrophages and conventional dendritic cells were likely critical for the resolution of ZIKV infection. The newly developed mouse and mosquito transmission models for ZIKV infection will be useful for the evaluation of antiviral drugs targeting the virus, vector, and host.

BACKGROUND:We present the first comprehensive analysis of Mycobacterium tuberculosis (MTB) isolates circulating in southern Taiwan. In this 9-year population-based study, the TB situation in the Kaohsiung region was characterized by genotypic analysis of 421 MTB isolates. METHODS:All 421 isolates of MTB were analyzed by spoligotyping and MIRU-VNTR typing. Drug-resistance patterns were also analyzed. RESULTS:The percentage of EAI (East African-Indian) strains increased across sampling years (2000-2008) in southern Taiwan, whereas the proportion of Beijing lineages remained unchanged. Clustering was more frequent with EAI genotype infections (odds ratio = 3.6, p

Tuberculosis incidence among aborigines is significantly higher than for Han Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB) strain characteristics contribute to this difference is not well understood. MTB isolates from aborigines and Han Chinese living in eastern and southern Taiwan, the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU-VNTR. In eastern Taiwan, 60% of aboriginal patients were ≤20 years old, significantly younger than the non-aboriginal patients there; aborigines were more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR) = 5.98, p

PURPOSE: To investigate risk factors associated with progressive visual field (VF) loss in primary angle closure glaucoma (PACG). METHODS: We retrospectively reviewed medical record of PACG patients who had ≥5 reliable VF examinations (central 24-2 threshold test, Humphrey Field Analyzer) and ≥2 years of follow-up. Each VF was scored using Collaborative Initial Glaucoma Treatment Study system. Progression was defined if 3 consecutive follow-up VF tests had an increased score of ≥3 above the mean of the first 2 VF scores. Factors associated with VF progression were evaluated by Cox proportional hazards models. RESULTS: A total of 89 eyes from 89 patients (mean age, 69.8 ± 7.9 years), who received a mean of 6.9 ± 2.3 VF tests (mean deviation at initial, -8.1 ± 4.4 dB) with a mean follow-up of 63.9 ± 23.9 months were included. VF progression was detected in 9 eyes (10%). The axial length (AL), anterior chamber depth, and intraocular pressure (IOP) in patients with and without progression were 22.5 ± 0.6 and 23.1 ± 0.9 mm, 2.5 ± 0.3 and 2.5 ± 0.3 mm, 14.8 ± 2.4 and 14.3 ± 2.3 mm Hg, respectively. AL was the only factor associated with progression in both Cox proportional hazards univariate (p = 0.031) and multivariate models (p = 0.023). CONCLUSION: When taking into account age, IOP, follow-up period, and number of VF tests, a shorter AL is the only factor associated with VF progression in this cohort of Chinese patients with PACG. Further studies are warranted to verify the role of AL in progressive VF loss in PACG.

Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71), which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA) are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD). A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. Secondly, infants are the target population of HFMD vaccines and it would need multi-national efficacy trials to prove clinical protection and speed up the licensure and usage of HFMD vaccines in children. An international network for enterovirus surveillance and clinical trials is urgently needed. Thirdly, EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies are warranted to clarify clinical and epidemiological significances of the antigenic and genetic variations between different EV71 genogroups, which is critical for vaccine design.

We present the first comprehensive analysis of Mycobacterium tuberculosis isolates circulating in the Kaohsiung region of southern Taiwan. The major spoligotypes found in the 224 isolates studied were Beijing lineages (n = 97; 43.3%), EAI lineages (n = 72; 32.1%) and Haarlem lineages (n = 18; 8.0%). By 24 MIRU-VNTR typing, 174 patterns were identified, including 24 clusters of 74 isolates and 150 unique patterns. The combination of spoligotyping and 12-MIRU-VNTR revealed that 129 (57.6%) of the 224 isolates were clustered in 18 genotypes. Moreover, 63.6% (7/11) of infected persons younger than 30 years had a Beijing strain, which could suggest recent spread among younger persons by this family of TB strains in Kaohsiung. Among the 94 Beijing family (SIT1, SIT250 and SIT1674) isolates further analyzed for SNPs by mass spectrometry, the most frequent strain found was ST10 (n = 49; 52%), followed by ST22 (n = 17; 18%) and ST19 (n = 11; 12%). Among the EAI-Manila family isolates analyzed by region deletion-based subtyping, the most frequent strain found was RD type 1 (n = 63; 87.5%), followed by RD type 2 (n = 9; 12.5%). In our previous study, the proportion of modern Beijing strains (52.5%) in northern Taiwan was significantly higher than the proportion of EAI strains (11%). In contrast, in the present study, EAI strains comprised up to 32% of Beijing strains in southern Taiwan. In conclusion, both 'modern' (Beijing) and 'ancient' (EAI) M. tuberculosis strains are prevalent in the Kaohsiung region, perhaps suggesting that both strains are somehow more adapted to southern Taiwan. It will be interesting to investigate the dynamics of the lineage composition by different selection pressures.