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Background: Recently, enterovirus 71 (EV71) has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups (A, B and C) and 11 genotypes (A, B1,B5 and C1,C5). In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998 (C2), 2000-2001 (B4), 2004-2005 (C4), and 2008 (B5). In this study, sera were collected to measure cross-reactive neutralizing antibody titers against different genotypes. Methods: We collected historical sera from children who developed an EV71 infection in 1998, 2000, 2005, 2008, or 2010 and measured cross-reactive neutralizing antibody titers against all 11 EV71 genotypes. In addition, we aligned and compared the amino acid sequences of P1 proteins of the tested viruses. Results: Serology data showed that children infected with genogroups B and C consistently have lower neutralizing antibody titers against genogroup A (.4-fold difference). The sequence comparisons revealed that five amino acid signatures (N143D in VP2; K18R, H116Y, D167E, and S275A in VP1) are specific for genogroup A and may be related to the observed antigenic variations. Conclusions: This study documented antigenic variations among different EV71 genogroups and identified potential immunodominant amino acid positions. Enterovirus surveillance and vaccine development should monitor these positions. [ABSTRACT FROM AUTHOR]

Background: Studies regarding coxsackievirus A6 (CVA6) infection were limited. In Taiwan, outbreaks of CVA6 occurred in 2009 and 2010, respectively, but the clinical manifestations were markedly different. We conducted a study to compare the clinical features and genomic sequence between the two years. Methodology/Principal Findings: In 2009 and 2010, 205 patients with coxsackievirus A6 (CVA6) infection were treated at Chang Gung Memorial Hospital. Detailed clinical features were obtained from 126 inpatients, 62 in 2009 and 64 in 2010. Between the inpatients in 2009 and 2010, no statistically significant difference was noted in terms of demographics, length of hospital stay and laboratory data. Significantly more patients in 2009 presented with herpangina (82%) while more patients in 2010 presented with hand-foot-mouth disease (HFMD; 67%) and skin rash beyond the typical sites for HFMD. Complete genomic sequences were determined and compared for three isolates from patients with herpangina in 2009 and three isolates from patients with HFMD in 2010. The complete sequences showed that 2009 and 2010 CVA6 isolates were indistinguishable by partial VP1 genes, but there were 5 unique nucleotide changes in 39 UTR, and 23 out of 2201 (1%) amino acids were different. 2010 viruses underwent the largest number of amino acid changes in 3CD protein, which is the precursor of both 3C protease and 3D polymerase. Conclusions: Since 2008 in Finland, outbreaks of HFMD due to CVA6 were noted internationally. CVA6 of different genetic background may cause different clinical manifestations such as herpangina and HFMD. [ABSTRACT FROM AUTHOR]

Background: Enteroviruses include over 100 serotypes and usually cause self-limited infections with non-specific symptoms in children, with the exceptions of polioviruses and enterovirus 71 which frequently cause neurologic complications. Therefore, early detection and serotyping of enteroviruses are critical in clinical management and disease surveillance. Traditional methods for detection and serotyping of enteroviruses are virus isolation and immunofluorescence assay, which are time-consuming. In this study, we compare virus isolation and two molecular tests for detection and serotyping of enteroviruses in clinical samples. Methods: One hundred and ten throat swabs were collected from pediatric outpatients with enterovirus-like illnesses (hand-foot-mouth disease, herpangina, and non-specific febrile illness). Virus isolation was conducted using multiple cell lines and isolated viruses were serotyped using immunofluorescent assay. In the molecular tests, a semi-nested RT-PCR and a novel CODEHOP platform were used to detect the 5'UTR and VP1 genes of enteroviruses, respectively. Amplified nucleotides were sequenced and genotyped. Results: Among the 110 cases, 39(35%), 52(47%), and 46(42%) were tested positive with these three tests, respectively. Using the consensus results of these three tests as the gold standard, agreement of the VP1 CODEHOP test was 96%, which is higher than those of the virus isolation (89%) and the 5'-UTR test (88%). The VP1 CODEHOP test also has the best performance on serotyping confirmed with serum neutralization tests. Conclusions: The VP1 CODEHOP test performed well for detection and serotyping of enteroviruses in clinical specimens and could reduce unnecessary hospitalization cares during enterovirus seasons. [ABSTRACT FROM AUTHOR]

A swine-origin influenza A was detected in April 2009 and soon became the 2009 H1N1 pandemic strain (H1N1pdm). The current study revealed the genetic diversity of H1N1pdm, based on 77 and 70 isolates which we collected, respectively, during the 2009/2010 and 2010/2011 influenza seasons in Taiwan. We focused on tracking the amino acid transitioning of hemagglutinin (HA) and neuraminidase (NA) genes in the early diversification of the virus and compared them with H1N1pdm strains reported worldwide. We identified newly emerged mutation markers based on A/California/04/2009, described how these markers shifted from the first H1N1pdm season to the one that immediately followed, and discussed how these observations may relate to antigenicity, receptor-binding, and drug susceptibility. It was found that the amino acid mutation rates of H1N1pdm were elevated, from 9.29x10-3 substitutions per site in the first season to 1.46x10-2 in the second season in HA, and from 5.23x10-3 to 1.10x10-2 in NA. Many mutation markers were newly detected in the second season, including 11 in HA and 8 in NA, and some were found having statistical correlation to disease severity. There were five noticeable HA mutations made to antigenic sites. No significant titer changes, however, were detected based on hemagglutination inhibition tests. Only one isolate with H275Y mutation known to reduce susceptibility to NA inhibitors was detected. As limited Taiwanese H1N1pdm viruses were isolated after our sampling period, we gathered 8,876 HA and 6,017 NA H1N1pdm sequences up to April 2012 from NCBI to follow up the dynamics of mentioned HA mutations. While some mutations described in this study seemed to either settle in or die out in the 2011-2012 season, a number of them still showed signs of transitioning, prompting the importance of continuous monitoring of this virus for more seasons to come. [ABSTRACT FROM AUTHOR]

This investigation evaluated the distributions of airborne adenovirus and Mycoplasma pneumoniae in public areas in the pediatric department of Children's Hospital in northern Taiwan. The airborne viral and bacterial concentrations were evaluated twice a week for a year using filter sampling with an airflow rate of 12 liters per minute for eight hours in the pediatric outpatient department and 24 hours in the pediatric emergency room. Real-time polymerase chain reaction assays were conducted for analysis. Approximately 18% of the air samples from the pediatric emergency room were found to contain adenovirus. Approximately forty-six percent of the air samples from the pediatric outpatient department contained Mycoplasma pneumoniae DNA products. High detection rates of airborne adenovirus DNA were obtained in July and August in the pediatric public areas. Airborne Mycoplasma pneumoniae was detected only in July in the pediatric emergency room and the peak levels were found from August to January in the pediatric outpatient department. Airborne particles that contained adenovirus and Mycoplasma pneumoniae were the most prevalent in the pediatric public areas. The potential relationship between these airborne viral/bacterial particles and human infection should be examined further. Keywords: adenovirus; Mycoplasma pneumoniae; filter sampling; real-time polymerase chain reaction; hospital; pediatric public areas. [ABSTRACT FROM AUTHOR]

Objective: Enterovirus 71 (EV71) is causing life-threatening outbreaks in tropical Asia. In Taiwan and other tropical Asian countries, although nationwide EV71 epidemics occur cyclically, age-specific incidence rates of EV71 infections that are critical to estimate disease burden and design vaccine trials are not clear. A nationwide EV71 epidemic occurred in 2008-09 in Taiwan, which provided a unique opportunity to estimate age-specific incidence rates of EV71 infections. Study Design: We prospectively recruited 749 healthy neonates and conducted follow-ups from June 2006 to December 2009. Sera were obtained from participants at 0, 6, 12, 24, and 36 months of age for measuring EV71 neutralizing antibody titers. If the participants developed suspected enterovirus illnesses, throat swabs were collected for virus isolation. Results: We detected 28 EV71 infections including 20 symptomatic and 8 asymptomatic infections. Age-specific incidence rates of EV71 infection increased from 1.71 per 100 person-years at 0-6 months of age to 4.09, 5.74, and 4.97 per 100 person-years at 7-12, 13-24, and 25-36 months of age, respectively. Cumulative incidence rate was 15.15 per 100 persons by 36 months of age, respectively. Conclusions: Risk of EV71 infections in Taiwan increased after 6 months of age during EV71 epidemics. The cumulative incidence rate was 15% by 36 months of age, and 29% of EV71 infections were asymptomatic in young children. [ABSTRACT FROM AUTHOR]

Background: The clinical diagnosis of influenza is difficult because it shares nonspecific symptoms with a variety of diseases. Emergency departments and clinics were overwhelmed by a surge of anxious patients during the 2009 influenza A virus (H1N1) outbreak. Our objective was to identify symptomatic predictors of influenza virus infection for patients with a negative rapid diagnostic test. Methodology/Principal Findings: We conducted a retrospective review of 805 patients who presented at Chang Gung Memorial Hospital, from August 1, 2009, to September 30, 2009. Respiratory specimens from these patients were subjected to rapid influenza tests and reverse-transcription polymerase chain reactions. In total, 36% of 308 children and 23% of 497 adults were positive for 2009 influenza A virus (H1N1) infection by polymerase chain reaction or virus culture. For pediatric patients, sore throat and influenza-like illness significantly increased the odds of having 2009 influenza A virus (H1N1) infection, by more than 3-fold (95% confidence interval (CI): 1.9-7.3) and 7-fold (95% CI: 4.00- 14.2), respectively. For adult patients, cough and constitutional symptoms increased the odds of having 2009 influenza A virus (H1N1) by greater than 5-fold (95% CI: 3.1-10.2) and 3-fold (95% CI: 2.1-6.7), respectively. The negative likelihood ratio of the combination of fever and cough was 0.096 (95% CI: 0.01-0.69) for children with negative results of rapid influenza diagnostic tests. Conclusion/Significance: In influenza epidemic settings, clinicians should be aware that rapid influenza diagnostic tests are relatively insensitive for the diagnosis of influenza virus infection. For patients with negative rapid influenza diagnostic tests, those lacking fever and cough have a low probability of influenza virus infection. The management strategy should be made individually and depend on the severity of illness. [ABSTRACT FROM AUTHOR]

Background: This study is to determine the seroprevalence of the pandemic influenza A H1N1 virus (pH1N1) in Taiwan before and after the 2009 pandemic, and to estimate the relative severity of pH1N1 infections among different age groups. Methodology/Principal Findings: A total of 1544 and 1558 random serum samples were collected from the general population in Taiwan in 2007 and 2010, respectively. Seropositivity was defined by a hemagglutination inhibition titer to pH1N1 (A/Taiwan/126/09) &ges;1:40. The seropositivity rate of pH1N1 among the unvaccinated subjects and national surveillance data were used to compare the proportion of infections that led to severe diseases and fatalities among different age groups. The overall seroprevalence of pH1N1 was 0.91% (95% confidence interval [CI] 0.43-1.38) in 2007 and significantly increased to 29.9% (95% CI 27.6-32.2) in 2010 (p<0.0001), with the peak attack rate (55.4%) in 10-17 year-old adolescents, the lowest in elderly &ges;65 years (14.1%). The overall attack rates were 20.6% (188/912) in unvaccinated subjects. Among the unvaccinated but infected populations, the estimated attack rates of severe cases per 100,000 infections were significantly higher in children aged 0-5 years (54.9 cases, odds ratio [OR] 4.23, 95% CI 3.04-5.90) and elderly &ges; 65years (22.4 cases, OR 2.76, 95% CI 1.99-3.83) compared to adolescents aged 10-17 years (13.0 cases). The overall case-fatality rate was 0.98 per 100,000 infections without a significant difference in different age groups. Conclusions/Significance: Pre-existing immunity against pH1N1 was rarely identified in Taiwanese at any age in 2007. Young children and elderly - the two most lower seroprotection groups showed the greatest vulnerability to clinical severity after the pH1N1 infections. These results imply that both age groups should have higher priority for immunization in the coming flu season. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen that causes severe morbidity and mortality in hospitalized patients. It is unclear whether repeated MRSA infections in pediatric patients are caused by relapse of previous infecting strains or by acquiring new strains from extrinsic sources. The study aimed to define the genetic relatedness of MRSA isolates from children with repeated infections. Methodology/Principal Findings: Children with multiple MRSA infections during 2004-2006 were identified in a teaching hospital. Repeated infections were confirmed by chart review and the responsible isolates were genotyped and screened for Panton-Valentine leukocidin (PVL) genes. Two consecutive episodes comprised an infection pair, and strain relatedness was defined for each pair as indistinguishable, highly related, or distinct if the isolates were of the same subtype, the same genotype, or different genotype, respectively. A total of 114 episodes comprising 66 infection pairs were identified in 48 children. The interval of infection pairs ranged from 15 days to 346 days, with a median duration of 57.5 days. Genotypings classified all isolates into 7 genotypes and 31 subtypes. Of 66 pairs, 46 (69.7%), 13 (19.7%) and 7 (10.6%) pairs were caused by indistinguishable, highly related and distinct strains, respectively. Subsequent infections caused by indistinguishable strains were more common for PVL-positive strains (17/18, 94.4%) than for PVL-negative strains (29/48, 60.4%, P = 0.007). The strain relatedness was not affected by the durations of interval between infections. Conclusions/Significance: Most repeated MRSA infections in children are caused by indistinguishable strains even after a long period of interval, suggesting that persistent carriage and relapse of initial infecting strains were responsible for the majority of recurrent MRSA infections. [ABSTRACT FROM AUTHOR]