Novel intertypic recombination of Echovirus 11 in the Enterovirus species B.

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.

Cost-effectiveness analysis of cell-based versus egg-based quadrivalent influenza vaccines in the pediatric population in Taiwan.

Cell-based influenza vaccines avoid egg-adaptive mutations, potentially improving vaccine effectiveness. We assessed the one-season cost-effectiveness of cell-based quadrivalent influenza vaccine (QIVc) against that of egg-derived quadrivalent influenza vaccines (QIVe) in children (6 months to 17 years of age) from payer and societal perspectives in Taiwan using an age-stratified static model. Base case and high egg adaptation scenarios were assessed. Deterministic and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratio (ICER) threshold in Taiwan was assumed to be USD 99 177/quality-adjusted life year (QALY). Compared to QIVe, QIVc would prevent 15 665 influenza cases, 2244 complicated cases, and 259 hospitalizations per year. The base case ICER was USD 68 298/QALY and USD 40 085/QALY from the payer and societal perspective, respectively. In the high egg adaptation scenario, the ICER was USD 45 782/QALY from the payer's perspective and USD 17 489/QALY from the societal perspective. Deterministic sensitivity analyses indicated that infection incidence rate, vaccination coverage, and prevalence of the A/H3N2 strain were the main drivers of ICER. In conclusion, switching the immunization strategy from QIVe to QIVc is predicted to reduce the influenza-associated disease burden and be cost-effective for the pediatric population in Taiwan. The potential benefits of QIVc would be even higher during influenza seasons with high levels of egg adaptation.

Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

Correction: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

[This corrects the article DOI: 10.1371/journal.ppat.1009352.].

Emergence of genotype C1 Enterovirus A71 and its link with antigenic variation of virus in Taiwan.

An outbreak of the hand-foot-mouth disease with severe neurological cases, mainly caused by the genotype C1 enterovirus A71 (EV-A71), occurred in Taiwan between 2018 and early 2019. In the recent decade, the most dominant EV-A71 genotypes in Taiwan were B5 and C4 but changed to C1 in 2018. Antibody-mediated immunity plays a key role in limiting the EV-A71 illness in humans. However, the level of neutralizing activities against genotype C1 virus by human polyclonal and monoclonal antibodies (MAbs) remains largely unclear. In the study, we demonstrated that that 39% (9 in 23) of post-infection sera from the genotype B5- or C4-infected patients in 2014-2017 exhibit reduced titers with the 2018-2019 genotype C1 viruses than with the earlier B5 and C4 viruses tested. This finding with polyclonal sera is confirmed with human MAbs derived from genotype B5 virus-infected individuals. The 2018-2019 genotype C1 virus is resistant to the majority of canyon-targeting human MAbs, which may be associated with the residue change near or at the bottom of the canyon region on the viral capsid. The remaining three antibodies (16-2-11B, 16-3-4D, and 17-1-12A), which target VP1 S241 on the 5-fold vertex, VP3 E81 on the 3-fold plateau and VP2 D84 on the 2-fold plateau of genotype C1 viral capsid, respectively, retained neutralizing activities with variable potencies. These neutralizing antibodies were also found to be protective against a lethal challenge of the 2018-2019 genotype C1 virus in an hSCARB2-transgenic mice model. These results indicate that the EV-A71-specific antibody response may consist of a fraction of poorly neutralizing antibodies against 2018-2019 genotype C1 viruses among a subset of previously infected individuals. Epitope mapping of protective antibodies that recognize the emerging genotype C1 virus has implications for anti-EV-A71 MAbs and the vaccine field.

Clinical and epidemiological features in hospitalized young children with acute gastroenteritis in Taiwan: A multicentered surveillance through 2014-2017.

BACKGROUND/PURPOSE: Acute gastroenteritis (AGE) remains a significant health issue in children. The worldwide evolution of pediatric AGE pathogens had been recorded since the introduction of rotavirus vaccine. Ten years after the rotavirus vaccine was introduced to the private sectors in Taiwan, a nationwide study was conducted to elucidate the epidemiological changes among major AGE pathogens. METHODS: From January 2014 to December 2017, children younger than 5 years old, hospitalized with AGE at 10 hospitals across Taiwan were enrolled. Stool specimens were tested for Salmonella spp., Campylobacter spp., Clostridiodes difficile, norovirus, and rotavirus by polymerase chain reaction (PCR). The epidemiological and clinical information was collected. RESULTS: Enteric pathogen were detected in 1983 (42.2%) of 4700 subjects, with Salmonella spp. (12.5%) being the leading cause of AGE, followed by norovirus (11.2%), rotavirus (8.7%), C. difficile (4.2%), Campylobacter spp. (1.0%), and a mixture of at least 2 of 5 above-mentioned pathogens (4.6%). The case distributions varied across different regions. In eastern Taiwan, rotavirus (21/131, 16.0%) remained the most common pathogen detected. The rotavirus vaccine uptake rate is significantly lower in patients with rotavirus AGE. Besides, rotavirus AGE frequently occurred in children with foreign parent(s), Taiwanese indigenous people, and those with the household monthly income < NT$ 60,000. CONCLUSION: Salmonella spp. and norovirus were two major pathogens of pediatric AGE in Taiwan during 2014-17. Providing low-to middle-income households with free rotavirus vaccine nationwide and an industry-led act to reduce salmonellosis should be considered by the authorities.

Staphylococcus aureus Keratitis in Taiwan: Genotyping, Antibiotic Susceptibility, and Clinical Features.

Staphylococcus aureus is an important pathogen for keratitis, a vision-threatening disease. We aimed to investigate the genotyping, antibiotic susceptibility, and clinical features of S. aureus keratitis, and to explore the possible role of Panton-Valentine leucocidin (PVL), a major virulence factor of S. aureus. We recruited 49 patients with culture-proven S. aureus keratitis between 2013 and 2017 at Chang Gung Memorial Hospital, Taiwan. PVL gene, multilocus sequence type (MLST), staphylococcal cassette chromosome mec (SCCmec), and pulsed-field gel electrophoresis (PFGE) were performed. Antibiotic susceptibility was verified using disk diffusion/E test. There were 49 patients with S. aureus keratitis; 17 (34.7%) were caused by methicillin-resistant S. aureus (MRSA) and 9 (18.4%) isolates had PVL genes. The predominant genotyping of MRSA isolates was CC59/PFGE type D/SCCmec VT/PVL (+). All methicillin-sensitive S. aureus (MSSA) and approximately 60% MRSA were susceptible to fluoroquinolones. No significant differences in clinical features, treatments, and visual outcomes were observed between MRSA/MSSA or PVL(+)/PVL(-) groups. In Taiwan, approximately one third of S. aureus keratitis was caused by MRSA, mainly community-associated MRSA. Although MRSA isolates were more resistant than MSSA, clinical characteristics were similar between two groups. Fluoroquinolones could be good empiric antibiotics for S. aureus keratitis.

Retrospective Seroepidemiology study of dengue virus infection in Taiwan.

BACKGROUND: Dengue virus infection has been an important and serious public health concern in Taiwan, where local outbreaks of dengue fever occurred almost every year. To our knowledge, no nationwide investigation has been carried out to determine the actual extent of infection in the general population. METHODS: A total of 1308 random serum samples were collected from the general population in Taiwan in 2010. The antibody-captured enzyme-linked immunosorbent assays were used to detect DENV-specific IgM and IgG. Demographics data were used for risk analysis. RESULTS: The weighted overall seroprevalence was 1.96% for anti-DENV IgM, and 3.4% for anti-DENV IgG, respectively. A significant rise of DENV IgG seropositive rate had been noted since late adulthood stage, from 1.1% at the age group of 50-59 years to 7.6% at the age group of 60-69 years. For people aged over 70 years, the seropositive rate reached 19%. Age, nationality, and regions of residency were associated with the IgG seropositivity. There was no statistically significant difference in seroprevalence of anti-Dengue IgM, indicating recent infection, among univariate predictors we proposed, including gender, age, residency, nationality, and household size. CONCLUSIONS: Our results indicated that the majority of population in Taiwan born after 1940 is naive to dengue virus and the prevalence of IgG antibody against dengue virus rises with age. Nationality, and regions of residency are associated with the exposure of population to infection by dengue viruses. Further studies are needed to realize the current situation of seroprevalence of dengue fever in Taiwan.

Detection and phylogeny of Staphylococcus aureus sequence type 398 in Taiwan.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) ST398 is a livestock associated-bacterium that is most prevalent in Europe. Human-adapted MRSA ST398 was recently reported from China, but there is no data available yet for Taiwan. METHODS: To identify S. aureus ST398 isolates, we examined 6413 S. aureus isolates (5632 MRSA and 781 susceptible strains) that were collected in Taiwan between 1995 and 2017. If isolates could not be typed by pulsed-field gel electrophoresis upon Sma I digestion, we performed further characterization and complete genome sequencing. RESULTS: We identified 18 ST398 S. aureus isolates from 16 subjects (0.28%), including 6 sensitive and 12 resistant strains. Of these, 14 were colonizing isolates, 3 were clinical (infecting) isolates and one isolate was from a pork specimen. All 3 infecting isolates were MSSA strains identified in 2015 from two children with recurrent otitis media or sinusitis. The other 3 MSSA isolates were identified from workers handling pork (2) or pork meat (1) in 2015. The first 5 MRSA colonizing isolates were identified from residents in two nursing homes in 2012. Six MRSA isolates were identified from residents and foreign employees at a nursing home in 2016 and one MRSA from a foreign worker in 2017. Phylogenetic analysis of genome sequences indicated that all 12 local ST398 MRSA strains cluster together, human-adapted and phylogenetically related to a human MRSA strain identified in China in 2002. Two local MSSA isolates could be linked to isolates from livestock. The toxin profiles were similar for the MRSA and MSSA isolates. CONCLUSIONS: Our results demonstrate that S. aureus ST398 was present in Taiwan in 2012 and potentially earlier. Although some isolates could be linked to livestock, most ST398 S. aureus isolates identified in Taiwan, particularly MRSA, represent human-adapted strains. Local transmission of human-adapted MRSA ST398 strains has occurred in nursing homes in Taiwan, possibly after import from China. Further surveillance is needed.

The potential role of pneumococcal conjugate vaccine in reducing acute respiratory inflammation in community-acquired pneumococcal pneumonia.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) reduces both invasive pneumococcal disease (IPD) and other pneumococcal infections worldwide. We investigated the impact of stepwise implementation of childhood PCV programs on the prevalence of pneumococcal pneumonia, severity of acute inflammation, and associations between breakthrough pneumonia and pneumococcal serotypes in Taiwan. METHODS: In total, 983 children diagnosed with community-acquired pneumococcal pneumonia were enrolled between January 2010 and December 2015. RESULTS: Proportions of pneumococcal vaccinations increased each year in age-stratified groups with PCV7 (32.2%) as the majority, followed by PCV13 (12.2%). The proportion of pneumococcal pneumonia decreased each year in age-stratified groups, especially in 2-5 year group. Serotype 19A is the leading serotype either in vaccinated (6.4%) or unvaccinated patients (5.2%). In particular, vaccinated patients had significantly higher lowest WBC, lower neutrophils, lower lymphocytes and lower CRP values than non-vaccinated patients (p < 0.05). After stratifying patients by breakthrough infection, those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia disease (p < 0.05). CONCLUSION: Systematic childhood pneumococcal vaccination reduced the prevalence of community-acquired pneumococcal pneumonia, especially in 2-5 year group. Serotype 19A was the major serotype for all vaccine types in patients with pneumococcal pneumonia and severity of acute inflammatory response was reduced in vaccinated patients.

Clinical features of gingivostomatitis due to primary infection of herpes simplex virus in children.

BACKGROUND: Primary herpetic gingivostomatitis (PHGS) in children, though usually self-limited, might mimic bacterial and enteroviral pharyngitis clinically. We conducted a study to define the clinical features of PHGS in children. METHODS: Between January 2012 and December 2016, 282 inpatients aged less than 19 years with cell culture-confirmed herpes simplex virus (HSV) infection in a medical center were identified from the virologic laboratory logbook. Clinical data were retrospectively collected. RESULTS: Among the 282 inpatients, 185 cases were considered as PHGS and were included for analysis. Fever was present in 99.5%. The mean duration of fever was 5.11 days (±2.24) with the longest being 17 days. Common oral manifestations included oral ulcers (84.3%), which equally resided in the anterior and posterior part of the oral cavity (65.4% vs. 63.2%), gum swelling and/or bleeding (67.6%), and exudate coated tonsils (16.8%). Leukocytosis (WBC count > 15,000/uL3) was noted in 52 patients (28.1%) and a serum C-reactive protein level > 40 mg/L in 55 patients (29.7%). Fixty-five patients (35%) were diagnosed with PHGS on admission and were significantly more likely to have ulcers over the anterior oral cavity (76.1% vs. 26.7%) and gum swelling/bleeding (76.2% vs. 7.5%, p-value all < 0.001) on admission and were significantly less likely to receive antibiotic treatment (16.9 vs. 36.7%, p-value < 0.01) than others. Forty-six patients (25%) undiagnosed as PHGS on discharge were significantly more likely to have exudate coated on the tonsils, to receive antibiotic treatment and significantly less likely to have gum swelling/bleeding and oral ulcers (all p-values < 0.01). CONCLUSIONS: Meticulously identifying specific oral manifestations of gum swelling/bleeding and ulcers over the anterior oral cavity in children can help making the diagnosis of PHGS earlier and subsequently reduce unnecessary prescription of antibiotics.

Methicillin-resistant Staphylococcus aureus nasal colonization among HIV-infected patients in Taiwan: prevalence, molecular characteristics and associated factors with nasal carriage.

BACKGROUND: To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan. METHODS: From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized. RESULTS: Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909-31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219-12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or VT, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). CONCLUSIONS: Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.

Hospital-based surveillance of severe rotavirus gastroenteritis and rotavirus strains in young Taiwanese children.

BACKGROUND/PURPOSE: Rotavirus remains a leading cause of pediatric gastroenteritis-related hospitalization. Surveillance studies have revealed that several major rotaviral genotypes are responsible for most cases of rotavirus gastroenteritis (RVGE). This study aimed to understand the characteristics of acute gastroenteritis (AGE) caused by rotavirus in young children in Taiwan. METHODS: Ten hospitals in Taiwan were subjected to prospective hospital-based AGE surveillance during 2014-2017, and children younger than 5 years old who were hospitalized due to AGE were enrolled in the study. Medical and demographic variables were recorded and analyzed, and stool specimens were collected for rotavirus identification and genotyping via real-time RT-PCR. Non-rotavirus AGE age-matched controls were enrolled. RESULTS: Surveillance identified 4747 young children hospitalized with AGE during this study period. The median age of these patients was 2.0 years. Rotavirus was detected in stool samples from 518 patients (10.9%). The prevalent months of RVGE in 2014, 2015, and 2017, wherein the rotavirus positivity rates exceeded 30%. The most common serotypes were G3P[8] (303/518, 58.9%) and G1P[8] (86/518, 16.6%). The percentage of G3P[8] increased from 4.9% in 2014 to 74.3% in 2016 (P < 0.0001), whereas the percentage of G1P[8] decreased from 61.0% in 2014 to 22.5% in 2015 (P < 0.0001). Compared with G3P[8], G1P[8] was associated with a significantly higher C-reactive protein level (P < 0.05). CONCLUSION: Rotavirus remains a notable pathogenic etiology of childhood AGE and the G3P[8] serotype was dominant in Taiwan. This study highlighted the importance of rotavirus surveillance to ensure protective effectiveness against the circulating strains.

Characteristics and etiology of hospitalized pediatric community-acquired pneumonia in Taiwan.

BACKGROUND/PURPOSE: The purpose of this study was to determine the pathogens and to estimate the incidence of pediatric community-acquired pneumonia (CAP) in Taiwan. METHODS: This prospective study was conducted at eight medical centers from November 2010 to September 2013. Children aged 6 weeks to 18 years who met the radiologic criteria for pneumonia were enrolled. To detect classical and atypical bacteria and viruses, blood and pleural fluids were cultured, and respiratory specimens were examined by multiple conventional and molecular methods. RESULTS: At least one potential pathogen was identified in 705 (68.3%) cases of 1032 children enrolled, including bacteria in 420 (40.7%) cases, virus in 180 (17.4%) cases, and mixed viral-bacterial infection in 105 (10.2%) cases. Streptococcus pneumoniae (31.6%) was the most common pathogen, followed by Mycoplasma pneumoniae (22.6%). Adenovirus (5.9%) was the most common virus. RSV was significantly associated with children aged under 2 years, S. pneumoniae in children aged between 2 and 5 years, and M. pneumoniae in children aged >5 years. The annual incidence rate of hospitalization for CAP was highest in children aged 2-5 years (229.7 per 100,000). From 2011 to 2012, significant reduction in hospitalization rates pertained in children under 5 years of age, in pneumonia caused by pneumococcus, adenovirus or co-infections and complicated pneumonia. CONCLUSION: CAP related pathogens have changed after increased conjugated pneumococcal vaccination rates. This study described the latest incidences and trends of CAP pathogens, which are crucial for prompt delivery of appropriate therapy.

Population dynamics at neuraminidase position 151 of influenza A (H1N1)pdm09 virus in clinical specimens.

Influenza A virus mutates rapidly, allowing it to escape natural and vaccine-induced immunity. Neuraminidase (NA) is a surface protein capable of cleaving the glycosidic linkages of neuraminic acids to release newly formed virions from infected cells. Genetic variants within a viral population can influence the emergence of pandemic viruses as well as drug susceptibility and vaccine effectiveness. In the present study, 55 clinical specimens from patients infected with the 2009 pandemic influenza A/H1N1 virus, abbreviated as A(H1N1)pdm09, during the 2015-2016 outbreak season in Taiwan were collected. Whole genomes were obtained through next-generation sequencing. Based on the published sequences from A(H1N1)pdm09 strains worldwide, a mixed population of two distinct variants at NA position 151 was revealed. We initially reasoned that such a mixed population may have emerged during cell culture. However, additional investigations confirmed that these mixed variants were detectable in the specimens of patients. To further investigate the role of the two NA-151 variants in a dynamic population, a reverse genetics system was employed to generate recombinant A(H1N1)pdm09 viruses. It was observed that the mixture of the two distinct variants was characterized by a higher replication rate compared to the recombinant viruses harbouring a single variant. Moreover, an NA inhibition assay revealed that a high frequency of the minor NA-151 variant in A(H1N1)pdm09 was associated with a reduced susceptibility to NA inhibitors. We conclude that two distinct NA-151 variants can be identified in patient specimens and that such variants may increase viral replication and NA activity.

Genomic analysis of serologically untypable human enteroviruses in Taiwan.

BACKGROUND: Human enteroviruses contain over 100 serotypes. We have routinely conducted enterovirus surveillance in northern Taiwan; but about 10% of isolates could not be serotyped using traditional assays. Next-generation sequencing (NGS) is a powerful tool for genome sequencing. METHODS: In this study, we established an NGS platform to conduct genome sequencing for the serologically untypable enterovirus isolates. RESULTS: Among 130 serologically untypable isolates, 121 (93%) of them were classified into 29 serotypes using CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer)-based RT-PCR to amplify VP1 genes (VP1-CODEHOP). We further selected 52 samples for NGS and identified 59 genome sequences from 51 samples, including 8 samples containing two virus genomes. We also detected 23 genome variants (nucleotide identity < 90% compared with genome sequences in the public domain) which were potential genetic recombination, including 9 inter-serotype recombinants and 14 strains with unknown sources of recombination. CONCLUSIONS: We successfully integrated VP1-CODEHOP and NGS techniques to conduct genomic analysis of serologically untypable enteroviruses.

Enterovirus A71 neurologic complications and long-term sequelae.

During recent 20 years, enterovirus A71 (EV-A71) has emerged as a major concern among pediatric infectious diseases, particularly in the Asia-Pacific region. The clinical manifestations of EV-A71 include uncomplicated hand, foot, and mouth disease, herpanina or febrile illness and central nervous system (CNS) involvement such as aseptic meningitis, myoclonic jerk, polio-like syndrome, encephalitis, encephalomyelitis and cardiopulmonary failure due to severe rhombencephalitis. In follow-up studies of patients with EV-A 71 CNS infection, some still have hypoventilation and need tracheostomy with ventilator support, some have dysphagia and need nasogastric tube or gastrostomy feeding, some have limb weakness/astrophy, cerebellar dysfunction, neurodevelopmental delay, lower cognition, or attention deficiency hyperactivity disorder. Long term sequelae may be related to greater severity of CNS involvement or neuron damage, hypoxia and younger age of onset.

Molecular characteristics and clinical features of pediatric methicillin-susceptible Staphylococcus aureus infection in a medical center in northern Taiwan.

BACKGROUND: There have been no reports regarding clinical features and molecular characteristics of childhood methicillin-susceptible Staphylococcus aureus (MSSA) infections in Taiwan. METHODS: We prospectively collected clinical S. aureus isolates from patients aged < 18 years in a university-affiliated hospital in 2015. Only the first isolate from each patient was included. Medical records were retrospectively reviewed. Patients were classified as community-associated (CA) or healthcare-associated (HA) by the epidemiologic criteria. All MSSA isolates were molecularly characterized. RESULTS: A total of 495 S. aureus isolates were identified, and 178 (36.0%) were MSSA. Among the 131 MSSA-infected patients enrolled, 94 (71.8%) were community-associated and 60 (45.8%) were inpatients. Patients with HA infections was significantly younger than those with CA infections (median, 15 vs. 67.5 months). The most common specimen of MSSA identified was pus or wound (73.3%). Compared to HA-MSSA, CA-MSSA isolates were significantly less frequently from sputum (6.4% vs. 27%, p = 0.001). Nineteen pulsotypes were identified. Four pulsotypes accounted for 60% of the isolates. Isolates of ST15/pulsotype F were more frequently seen in CA than in HA (p = 0.064) while isolates of ST188/pulsotype AX frequently seen in HA (p = 0.049). PVL genes were identified in 11 isolates (8.4%), nine of which were characterized as ST59/pulsotype D, same as the local endemic CA-MRSA clone. CONCLUSIONS: MSSA accounted for around one-third of childhood S. aureus infections in northern Taiwan. SSTI was the most common manifestation. The molecular characteristics of these clinical MSSA isolates were relatively diverse and had certain significant differences between CA and HA isolates.

Genomic analysis of enterovirus D68, including one strain isolated from a child with Wilson's disease in Taiwan.

North America experienced life-threatening outbreaks of enterovirus D68 (EV-D68) in 2014. We retrospectively detected EV-D68 from a child with Wilson's disease in 2008 in Taiwan. After comparing this EV-D68/Taiwan/2008 strain with EV-D68 genomes obtained from the public domain, it was classified as genome type 1-B; it is phylogenetically related to the predominant EV-D68 viruses that circulated in 2009 in Vietnam. It is necessary to strengthen EV-D68 detection globally, including in children with acute liver failure. Moreover, harmonization of genomic analysis of EV-D68 is desirable to understand global evolution of EV-D68.

Burden of Severe Norovirus Disease in Taiwan, 2003-2013.

Background: Despite the increasingly recognized role of norovirus in global acute gastroenteritis (AGE), specific estimates of the associated disease burden remain sparse, primarily due to limited availability of sensitive norovirus diagnostics in the clinical setting. We sought to estimate the incidence of norovirus-associated hospitalizations by age group in Taiwan using a previously developed indirect regression method. Methods: AGE-related hospitalizations in Taiwan were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes abstracted from a national database; population data were provided from the Department of Household Registration Affairs. Population and hospitalizations were aggregated by month and year (July 2003-June 2013) and grouped by age: <5 years, 5-19 years, 20-64 years, and ≥65 years. Monthly counts of cause-unspecified AGE hospitalizations were modeled as a function of counts of known causes, and the residuals were then analyzed to estimate norovirus-associated hospitalizations. Results: Over the study period, an annual mean of 101400 gastroenteritis-associated hospitalizations occurred in Taiwan (44 per 10000 person-years), most of which (83%) had no specified cause. The overall estimated rate of norovirus-associated hospitalizations was 6.7 per 10000 person-years, with the highest rates in children aged <5 years (63.7/10000 person-years). Predicted norovirus peaked in 2006-2007 and 2012-2013. Conclusions: Our study is one of the first to generate a population-based estimate of severe norovirus disease incidence in Asia, and highlights the large burden of norovirus in Taiwan, particularly in children. Predicted peak norovirus seasons coincided with the emergence of new strains and resulting pandemics, supporting the validity of the estimates.