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Background: Human parainfluenza viruses (HPIVs) commonly cause childhood respiratory illness requiring hospitalization in Taiwan. This study aimed to investigate clinical severity and identify risk factors predisposing to severe disease in hospitalized children with HPIV infection. Methods: We included hospitalized patients with lab-confirmed HPIV infection from 2007 to 2018 and collected their demographic and clinical characteristics. Patients with ventilator support, intravenous inotropic agents, and extracorporeal membrane oxygenation were defined as severe cases. Results: There were 554 children hospitalized for HPIV infection. The median age was 1.2 years; 518 patients had non-severe HPIV infection, whereas 36 patients (6.5%) had severe HPIV infection. 266 (48%) patients had underlying diseases, and 190 patients (34.3%) had bacterial co-detection. Children with severe HPIV infection were more likely to have bacterial co-detection than those without (52.8% vs 33.0%, p = 0.02). Patients with lung patch or consolidation had more invasive bacterial co-infection or co-detection than those without patch or consolidation (43% vs 33%, p = 0.06). Patients with neurological disease (adjusted OR 4.77, 95% CI 1.94–11.68), lung consolidation/patch (adjusted OR 6.64, 95% CI 2.80–15.75), and effusion (adjusted OR 11.59, 95% CI 1.52–88.36) had significantly higher risk to have severe HPIV infection. Conclusion: Neurological disease and lung consolidation/patch or effusion were the most significant predictors of severe HPIV infection.

Introduction: COVID-19 poses risks and leads to complications for vulnerable populations, including children. Unreported cases of COVID-19 among children hinder our understanding of the true disease burden. In this study, we aimed to investigate the proportion of children who report no prior infection to SARS-CoV-2 but who nevertheless exhibit serological evidence of prior infection. Methods: Between November 2022 and February 2023, we recruited children and adolescents under 19 years of age who lacked a prior history of SARS-CoV-2 infection. Participants underwent SARS-CoV-2 antibody testing to assess the presence of IgG antibodies specific to nucleocapsid (N) and spike (S) proteins. Demographic and contact information were also collected. Results: Among 260 COVID-19-free children, the overall anti-N antibody positivity rate, which varied across age groups (4%–25%), was 9.2% (24/260). Contact with individuals who were positive for COVID-19, particularly the children's mothers, significantly increased the likelihood of antibody positivity. The median age of the 34 children who remained unvaccinated against COVID-19 was lower than that of the children who were vaccinated (6.5 vs. 9 years; p

Abstract Background Kawasaki disease (KD) is the most important acquired heart disease in children. This study investigated annual incidence, seasonality, secular trend and the correlation of KD incidence with viral activity in Taiwan. Methods Through the national health insurance database, we identified KD during 2001–2020. The viral activity was obtained from nationwide surveillance database. We analyzed KD age-specific annual incidence, secular trends, seasonality and the correlation between KD incidence and common enteric or respiratory viral activity. Results The KD incidence of subjects younger than 18 years significantly increased from 2001 to 2020 (11.78 and 22.40 per 100,000 person-years, respectively), and substantially decreased with age. Infants younger than 1 year presented the highest KD annual incidence at 105.82 to 164.34 per 100,000 person-years from 2001 to 2020. For all KD patients, the most frequently occurring season was summer followed by autumn. The KD incidence of infants younger than 1 year had significantly positive correlation with enteric (r = 0.14) and respiratory (r = 0.18) viral activity. Conclusions This study demonstrates the increasing trend of KD annual incidence and seasonality (more in summer and autumn) in Taiwan. The activity of common respiratory and enteric viruses was significantly correlated with KD incidence in infants.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients’ clinical manifestations and identify risk factors for shock. Methods: We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups. Results: We enrolled 28 patients, including 13 (46 %) with shock and 15 (54 %) without shock. The median age was 6.4 years (IQR: 1.9–7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95 % CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77 %, specificity 93 %, positive predictive value 91 %, negative predictive value 82 %. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95 % CI, 1.01–668.89). Conclusions: MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission.

Background: Cases of glomerulopathy after COVID-19 vaccination have been reported in the adult population, while only a few cases have been reported in children and adolescents. For better understanding of this association in pediatric population, we aimed to describe clinical course of patients with glomerulopathy within 60 days of COVID-19 vaccination who were under followed up in the pediatric nephrology department of National Taiwan University Children's Hospital. Methods: We reviewed the clinical characteristics, vaccine types, and outcomes of patients with newly diagnosed glomerular diseases or relapse of underlying glomerulopathy within 60 days after COVID-19 vaccination at our facility between January 2021 and July 2022. Results: Thirteen pediatric patients were found to have newly diagnosed glomerular diseases or relapse from their underlying glomerulopathy after receiving their first, second, or third COVID-19 vaccines in our facility. Of the five pediatric patients with newly diagnosed glomerulopathy after vaccination, thin basement membrane nephropathy, idiopathic nephrotic syndrome, and hematuria have been identified. Seven patients had relapse episodes of underlying nephrotic syndrome and one patient with underlying isolated microscopic hematuria developed subnephrotic proteinuria after COVID-19 vaccination. All patients experienced remission or improvement with either immunosuppressive or conservative treatment during the follow-up period. Conclusions: This is the largest case series to date of pediatric glomerulopathy after COVID-19 vaccination. From our report, patients with either newly diagnosed or relapse of glomerulopathy after vaccination had good outcomes, and receiving vaccination to prevent COVID-19 infection or complications should be encouraged in pandemic era under close monitoring kidney manifestations.

Background: Since April 2022, a notable increase in COVID-19 cases with the rapid spread of the SARS-CoV-2 Omicron variant has been reported in Taiwan. In the epidemic, children were one of the most vulnerable groups, so we analyzed their clinical presentations and factors associated with severe complications of COVID-19 in children. Methods: We included hospitalized patients under 18 years old with lab-confirmed SARS-CoV-2 infection from March 1, 2022, to July 31, 2022. We collected the demographic and clinical characteristics of the patients. Patients requiring intensive care were defined as severe cases. Results: Among the 339 enrolled patients, the median age was 31 months (interquartile range (IQR), 8–79.0 months); and 96 patients (28.3%) had underlying diseases. Fever was noted in 319 patients (94.1%) with a median duration of two days (IQR 2–3 days). Twenty-two patients (6.5%) were severe cases, including 10 patients (2.9%) with encephalopathy with abnormal neuroimaging and ten patients (2.9%) with shock. Two patients (0.6%) died. Patients with congenital cardiovascular disease (aOR: 21.689), duration of fever up to four days or more (aOR: 6.466), desaturation (aOR: 16.081), seizure (aOR: 20.92), and procalcitonin >0.5 ng/mL (aOR: 7.886) had a higher risk of severe COVID-19. Conclusions: Vital signs need close monitoring, early management and/or intensive care may be applied in COVID-19 patients with congenital cardiovascular diseases, fever lasting ≥4 days, seizures, desaturation and/or elevated procalcition since they are at higher risks of severe diseases.

Background: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. Methods: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. Results: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. Conclusion: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Background: Maternal transplacental antibody is an important origins of passive immunity against neonatal enterovirus infection. Echovirus 11 (E11) and coxsackievirus B3 (CVB3) are important types causing neonatal infections. There were few investigations of enterovirus D68 (EVD68) infection in neonates. We aimed to investigate the serostatus of cord blood for these three enteroviruses and evaluate the factors associated with seropositivity. Methods: We enrolled 222 parturient (gestational age 34–42 weeks) women aged 20–46 years old between January and October 2021. All participants underwent questionnaire investigation and we collected the cord blood to measure the neutralization antibodies against E11, CVB3 and EVD68. Results: The cord blood seropositive rates were 18% (41/222), 60% (134/232) and 95% (211/222) for E11, CVB3 and EVD68, respectively (p

Background: Acute respiratory infections (ARIs) are common in children. We developed machine learning models to predict pediatric ARI pathogens at admission. Methods: We included hospitalized children with respiratory infections between 2010 and 2018. Clinical features were collected within 24 h of admission to construct models. The outcome of interest was the prediction of 6 common respiratory pathogens, including adenovirus, influenza virus types A and B, parainfluenza virus (PIV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP). Model performance was estimated using area under the receiver operating characteristic curve (AUROC). Feature importance was measured using Shapley Additive exPlanation (SHAP) values. Results: A total of 12,694 admissions were included. Models trained with 9 features (age, event pattern, fever, C-reactive protein, white blood cell count, platelet count, lymphocyte ratio, peak temperature, peak heart rate) achieved the best performance (AUROC: MP 0.87, 95% CI 0.83–0.90; RSV 0.84, 95% CI 0.82–0.86; adenovirus 0.81, 95% CI 0.77–0.84; influenza A 0.77, 95% CI 0.73–0.80; influenza B 0.70, 95% CI 0.65–0.75; PIV 0.73, 95% CI 0.69–0.77). Age was the most important feature to predict MP, RSV and PIV infections. Event patterns were useful for influenza virus prediction, and C-reactive protein had the highest SHAP value for adenovirus infections. Conclusion: We demonstrate how artificial intelligence can assist clinicians identify potential pathogens associated with pediatric ARIs upon admission. Our models provide explainable results that could help optimize the use of diagnostic testing. Integrating our models into clinical workflows may lead to improved patient outcomes and reduce unnecessary medical costs.

Background: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan. Methods: This retrospective case–control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors. Results: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p

Objectives: The SARS-CoV-2 Omicron variant pandemic struck Taiwan in April 2022. Rapid antigen tests (RATs) play an important role in providing rapid results during a pandemic. However, self-collected samples by the children's caregivers without the supervision of medical personnel raise some concerns. Methods: This study was performed to investigate household transmission, clinical characteristics, and antigen performance in a special COVID-19 family clinic in a children's hospital. The performance of at-home RATs was evaluated based on reverse transcription-polymerase chain reaction. Results: We included 627 patients in our study between May 11 and June 10, 2022. The COVID-19 full vaccination rate was significantly higher in adults (98.5%) than in children (5.9%, P

Abstracts: Background/purpose: Clinical data on carbapenem-resistant Enterobacterales (CRE) bacteremia in the pediatric population are limited. This study investigated the clinical characteristics and outcomes of pediatric CRE bacteremia. Methods: Clinical data on bacteremia caused by carbapenem-susceptible and carbapenem-resistant Enterobacterales, including Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia marcescens, Proteus mirabilis, Citrobacter spp., and Morganella spp., in pediatric patients from a children's hospital in Taiwan were retrospectively retrieved and analyzed. Results: From January 2013 to December 2021, 471 clinical isolates of Enterobacterales bacteremia were identified in 451 episodes from 379 pediatric patients. Among all the isolates, the predominant species were E. coli (199/471, 42.2%), Klebsiella spp. (168/471, 35.6%), and Enterobacter spp. (59/471, 12.5%), with carbapenem-resistance rates of 1.5%, 11.9%, and 25.0%, respectively. Overall, 40 (8.4%) showed a carbapenem resistance phenotype. Patients’ all-cause mortality rate at 14 days was significantly higher in CRE bacteremia episodes than non-CRE ones (12.5% vs. 3.6%, p

Background: Mycoplasma pneumoniae is a pathogen that causes respiratory diseases in children. Infections caused by M. pneumoniae are usually self-limited but occasionally can be severe. We observed emerging cases of severe mycoplasma infection requiring extracorporeal membrane oxygenation (ECMO). Thus, we investigated chronological changes in the molecular features of the M. pneumoniae and its clinical impacts among the pediatric population. Methods: From 2011 to 2019, respiratory samples were collected from patients younger than 18 years old with pneumonia in a tertiary children's hospital. Focused multiple-locus variable number of tandem repeats analysis (MLVA) typing was performed on samples positive for M. pneumoniae in 2016 and 2019. Clinical data from the patients' electronic medical records were collected. We described the annual trend of macrolide resistance and MLVA type and analyzed the associations between clinical manifestations and MLVA types. Results: The percentage of macrolide-resistant (MLR) M. pneumoniae gradually increased from 22% (27/122) in 2015 to 70% (82/117) in 2019. Among the MLR M. pneumoniae, the predominant strain shifted from type P (31% [13/42]) to type A (40% [19/46]). The demographics, initial presentations, and clinical courses of the subjects with MLR M. pneumoniae did not differ significantly between 2011 and 2019. However, in 2019, two fulminant cases requiring venovenous ECMO were observed, which indicates that more attention to the clinical severity of MLR M. pneumoniae infections is warranted. Conclusion: Obtaining accurate information on macrolide susceptibility is crucial for physicians to initiate appropriate antibiotic treatment in a timely fashion. Although we could not identify significant differences among mycoplasma pneumonias caused by different MLVAs over a span of 9 years, the emergence of severe mycoplasma infections requiring ECMO was clinically significant, and further monitoring was required.

Abstract Background Enterovirus A71 (EV A71) is one of the most important enteroviruses related to morbidity and mortality in children worldwide. This study aimed to analyse the secular trend of EV A71 in Taiwan from 1998 to 2020 and to evaluate the effectiveness of infection control measures. Methods We collected the epidemiological data of EV A71 from disease surveillance systems in Taiwan. We analysed the association between the secular trend of EV A71 and preventive measures such as hand washing, case isolation, and suspension of classes. Results The incidence of enterovirus infections with severe complications (EVSC) decreased from 16.25 per 100,000 children under six in 1998 to less than 9.73 per 100,000 children under six after 2012 (P = 0.0022). The mortality rate also decreased significantly, from 3.52 per 100,000 children under six in 1998 to 0 per 100,000 children under six in 2020 (P

Background: Recurrent pneumonia is uncommon in children and few studies investigate the clinical impact of underlying diseases on this issue. This study aimed to explore the difference in clinical manifestations, pathogens, and prognosis of recurrent pneumonia in children with or without underlying diseases. Methods: We conducted a retrospective study of pediatric recurrent pneumonia from 2007 to 2019 in National Taiwan University Hospital. Patients under the age of 18 who had two or more episodes of pneumonia in a year were included, and the minimum interval of two pneumonia episodes was more than one month. Aspiration pneumonia was excluded. Demographic and clinical characteristics of patients were collected and compared. Results: Among 8508 children with pneumonia, 802 (9.4%) of them had recurrent pneumonia. Among these 802 patients, 655 (81.7%) had underlying diseases including neurological disorders (N = 252, 38.5%), allergy (N = 211, 32.2%), and cardiovascular diseases (N = 193, 29.5%). Children without underlying diseases had more viral bronchopneumonia (p < 0.001). Children with underlying diseases were more likely to acquire Staphylococcus aureus (p = 0.001), and gram-negative bacteriae, more pneumonia episodes (3 vs 2, p < 0.001), a longer hospital stay (median: 7 vs. 4 days, p < 0.001), a higher ICU rate (28.8% vs 3.59%, p < 0.001), and a higher case-fatality rate (5.19% vs 0%, p < 0.001) than those without underlying diseases. Conclusion: Children with underlying diseases, prone to have recurrent pneumonia and more susceptible to resistant microorganisms, had more severe diseases and poorer clinical outcomes. Therefore, more attention may be paid on clinical severity and the therapeutic plan.

Background/purpose: Influenza is frequently complicated with bacterial co-infection. This study aimed to disclose the significance of Streptococcus pneumoniae co-infection in children with influenza. Methods: We retrospectively reviewed medical records of pediatric patients hospitalized for influenza with or without pneumococcal co-infection at the National Taiwan University Hospital from 2007 to 2019. Clinical characteristics and outcomes were compared between patients with and without S. pneumoniae co-infection. Results: There were 558 children hospitalized for influenza: 494 had influenza alone whereas 64 had S. pneumoniae co-infection. Patients with S. pneumoniae co-infection had older ages, lower SpO2, higher C-Reactive Protein (CRP), lower serum sodium, lower platelet counts, more chest radiograph findings of patch and consolidation on admission, longer hospitalization, more intensive care, longer intensive care unit (ICU) stay, more mechanical ventilation, more inotropes/vasopressors use, more surgical interventions including video-assisted thoracoscopic surgery (VATS) and extracorporeal membrane oxygenation (ECMO), and higher case-fatality rate. Conclusion: Compared to influenza alone, patients with S. pneumoniae co-infection had more morbidities and mortalities. Pneumococcal co-infection is considered when influenza patients have lower SpO2, lower platelet counts, higher CRP, lower serum sodium, and more radiographic patches and consolidations on admission.

Background: Respiratory syncytial virus (RSV) is a common cause of childhood pneumonia, but there is limited understanding of whether bacterial co-infections affect clinical severity. Methods: We conducted a retrospective cohort study at National Taiwan University Hospital from 2010 to 2019 to compare clinical characteristics and outcomes between RSV with and without bacterial co-infection in children without underlying diseases, including length of hospital stay, intensive care unit (ICU) admission, ventilator use, and death. Results: Among 620 inpatients with RSV pneumonia, the median age was 1.33 months (interquartile range, 0.67–2 years); 239 (38.6%) under 1 year old; 366 (59.0%) males; 201 (32.4%) co-infected with bacteria. The three most common bacteria are Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae. The annually seasonal analysis showed that spring and autumn were peak seasons, and September was the peak month. Compared with single RSV infection, children with bacterial co-infection were younger (p = 0.021), had longer hospital stay (p

Long-term neurological and neurodevelopmental sequelae are a concerning issue for people with Enterovirus A71 (EV-A71) central nervous system (CNS) infection. Unfortunately, no longitudinal prospective clinical study has systematically investigated the consequences of EV-A71 CNS infection during early life on the later development of other psychiatric disorders. In this naturalistic longitudinal follow-up design, we followed forty-three youth, who got EV-A71 CNS involvement 6–18 years ago and were enrolled in other EV-A71 clinical studies then. Their psychiatric presentation, emotional/behavioral problems, and cognitive issues were examined using a psychiatrist-conducted diagnostic interview, parent- and self-rated questionnaires, and neuropsychological tests, respectively. We compared the prevalence of psychiatric disorders in youth with EV-A71 CNS involvement to a nationally representative cohort. Emotion/behavior and cognition in EV-A71-CNS-infected youth were compared to those in a matched community-based sample of healthy controls and youth with attention-deficit/hyperactivity disorder (ADHD). Compared to a national sample (absolute ADHD prevalence 10.1%), youth with EV-A71 CNS involvement had three times the odds of receiving an ADHD diagnosis (standardized prevalence ratio, 95% CI = 1.8, 4.2; absolute ADHD prevalence 34.9%). No other psychiatric diagnoses were more common in EV-A71-CNS-infected youth. Compared to community-based ADHD youth, EV-A71-CNS-infected youth with psychiatric disorders showed comparable core ADHD symptoms, opposition/defiance, autistic features, and suboptimal sustained attention performance (based on the Conners’ Continuous Performance Test), all of which were more severe than healthy controls. EV-A71-CNS-infected youth without psychiatric disorders showed comparable autistic features to EV-A71-CNS-infected youth with psychiatric disorders and ADHD youth. EV-A71 CNS involvement may cause long-term, adverse psychiatric outcomes that develop into an ADHD diagnosis alongside social/communication/emotion problems and autistic features. We recommend earlier identification and intervention of these problems among these children.

Background/purpose(s): This study aimed to investigate clinical features and antimicrobial susceptibility of inpatient children with nontyphoidal salmonellosis from 2010 to 2018. Methods: We retrospectively collected pediatric patients with nontyphoidal Salmonella infection confirmed by positive cultures in a tertiary medical center in Taiwan from 2010 to 2018. Patients' characteristics, clinical manifestations, and laboratory data were collected. Serogroup category and antimicrobial susceptibility were also analyzed. Results: Of total 569 isolates, ampicillin resistant rate was 53% in average, third-generation cephalosporin resistant rate was 6.7%, ciprofloxacin resistant rate was 9% and trimethoprim–sulfamethoxazole resistant rate was 30%. Compared to the resistant rates in 2010, the resistance rate of third generation cephalosporin was significantly higher (3.4% vs. 11%, p = 0.003) but that of ciprofloxacin was significantly lower (20% vs. 11%, p

Background/Purpose: Despite the high prevalence of Mycoplasma pneumoniae infections, reports on severe life-threatening M. pneumoniae pneumonia (MPP) in children are limited. Methods: We retrospectively enrolled pediatric patients with PCR-positive MPP requiring ICU admission in a children's hospital in Taipei, Taiwan from Jun 2010 to October 2019. Clinical manifestations and laboratory data of severe MPP were analyzed. Macrolide susceptibility was determined by genotyping, and its relationship with clinical manifestations was also analyzed. Results: Approximately 5% (34/658) children hospitalized for MPP required ICU admission. Compared with non-ICU cases (n = 291), ICU cases (n = 34) were associated with more underlying conditions, more pleural effusion, longer fever duration, longer hospital stay, the requirement of second-line antibiotic treatment, and delayed effective and second-line antibiotic treatment. Macrolide resistance was similar in ICU and non-ICU groups (53% vs 53%; p = 0.986). In severe MPP, patients requiring endotracheal intubation were associated with more septic shock, empyema, ARDS, prolonged fever after effective antibiotic treatment, delayed second-line and effective antibiotic treatment. In 18 of the 22 patients with pleural fluid analysis, the pleural effusion was alkaline (pH > 7.7) and lymphocyte-predominant. Conclusion: M. pneumoniae infection can cause severe life-threatening pneumonia in children. Delayed effective and second-line antibiotic treatments are associated with severe life-threatening MPP.

Purpose: To investigate the clinical feature of tuberculosis and BCG adverse effects in children and to examine whether delayed BCG vaccination changes the incidence of BCG osteomyelitis. Methods: We analyzed patients younger than 18 years with tuberculosis or BCG-associated adverse effects from 2008 to 2019. We compared their clinical features, laboratory tests and outcomes. Results: Totally 137 patients were collected, with 27% of pulmonary tuberculosis (PTB), 31% of extrapulmonary tuberculosis (EPTB) and 42% of BCG-associated adverse effects. The median age was older in PTB than EPTB group (17.1 vs 15.4 years; p = 0.015). More patients in EPTB group had fever than PTB group (55% vs 25%; p = 0.008). Compared with exclusively EPTB, more patients in EPTB plus PTB group had fever (78% vs 38%; p = 0.009), and had more systemic symptoms (67% vs 25%; p = 0.007), lower absolute lymphocyte count (1230 vs 1850/μL; p = 0.033), higher CRP level (5.62 vs 2.21 mg/dL; p = 0.024) and longer hospital stay (20 vs 11 days; p = 0.031). In BCG osteomyelitis group, the median time interval from vaccination to diagnosis was 16.4 months (IQR 15.0–20.2). Age at vaccination, either at birth or 5-8 month-old, did not affect the proportion of BCG osteomyelitis among children with BCG-associated adverse effects. Conclusion: Children with EPTB plus PTB had more fever, lower lymphocyte count and higher CRP. The median time interval from vaccination to diagnosis of BCG osteomyelitis was 16.4 months and the proportion of BCG osteomyelitis among children with BCG-associated adverse effects was not affected by delayed vaccination in this study.

Abstract Background The Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children. Methods The incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods. Results The incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008–June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67–0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5–44.7%), 33.9% (95% CI: 25.2–41.5%) and 43.4% (95% CI: 34.4–51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5–55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2–85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008–June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2–72.3%). Conclusions PPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children.

Abstract Haemophilus influenzae is a predominant pathogen for conjunctivitis, acute otitis media and acute bacterial paranasal sinusitis in children. We undertook this study to investigate the possible association among these diseases. Children younger than 18-year-old with a diagnosis of bacterial conjunctivitis plus acute otitis media and/or acute bacterial paranasal sinusitis during 2009–2018 were included. Sampling for bacterial cultures was obtained from the lower palpebral conjunctiva and/or ear discharge with cotton-tipped swabs. A total of 67 children were recruited and the age was 29.5 (± 22.4) months in average. Fifty-seven children had conjunctivitis–otitis media syndrome and eight of them had a concurrent diagnosis of acute paranasal sinusitis. Ten children had conjunctivitis and acute paranasal sinusitis simultaneously. Clusters in household were observed in 50.7% children. Most common isolates were Haemophilus influenzae (70%), Moraxella catarrhalis (18%), and Staphylococcus aureus (8%). Antibiotic resistance rate of H. influenzae was 80% for ampicillin, 18% for amoxicillin–clavulanate, and 11% for the second or third-generation cephalosporins. Apart from well-known conjunctivitis–otitis media syndrome, acute paranasal sinusitis may also be linked to conjunctivitis with a similar pathogenic process. Simultaneous presence of these infections may guide the choice of empiric antibiotics toward H. influenzae.

Background/purpose: Early identification of pathogens causing bloodstream infection (BSI) is critical for prompt administration of appropriate antimicrobial therapy. Methods: We used an in-house saponin-based extraction method to evaluate the performance of Bruker Biotyper MALDI-TOF MS system (MALDI Biotyper) for bacterial and fungal identification in 2013 positively-flagged VersaTREK blood culture bottles. Results: A total of 180 monomicrobial and 23 polymicrobial positive blood cultures were investigated. Among monomicrobial positive blood cultures, the MALDI Biotyper recognized 90.6% and 81.7% of organisms directly from the flagged blood culture bottles to the genus and species levels, respectively. The MALDI Biotyper also correctly characterized one of the polymicrobial organisms to the species level in 20 (87%) bottles and to the genus level in 21 (91.3%) bottles. The overall identification rate using our protocol was 90.6% (184/203) and 82.3% (167/203) for genus and species levels, respectively. Identification accuracy was higher for Gram-positive than Gram-negative organisms and was the lowest for yeasts. Score values of identification were ≥1.500 for 200 (98.5%) bottles, ≥1.700 for 195 (96.1%) bottles and ≥2.000 for 182 (89.7%) bottles. Moreover, 83.5% and 92% of the isolates were identified precisely to species and genus level with the lower cutoff score of 1.500. Using our protocol also helped identifying BSI pathogens 18–24 h earlier compared to the sub-cultured colonies. Conclusion: Using Bruker MALDI Biotyper for identification of isolates directly from positive VersaTREK blood culture bottles, our in-house saponin-based protocol provided a more rapid turn-around time for correct identification of BSI pathogens than the conventional methods.

Background: Reports on the effectiveness of pneumococcal conjugate vaccines (PCVs) on pediatric parapneumonic effusion are limited. We report the changes in cases and etiologies of pediatric parapneumonic effusion in a children's hospital before and after national PCV13 vaccination programs. Methods: We screened medical records of children 0–18 years admitted to the National Taiwan University Hospital with diagnoses of lobar pneumonia and parapneumonic effusion between 2008 and 2017. Patients with effusion analyses were included. Results of blood, pleural fluid, and respiratory specimens surveyed as standard care were analyzed. Results: Diagnostic testing revealed at least a pathogen in 85% of 202 children with lobar pneumonia and parapneumonic effusion. After national PCV13 immunization, pneumococcal empyema decreased by 72% among 2- to 5-year olds. Mycoplasma pneumoniae was the second most common etiology. There were marked differences in effusion characteristics, metabolic, and respiratory parameters between children infected with pneumococcus and M. pneumoniae. Conclusion: The effectiveness of the national PCV13 immunization programs on pneumococcal empyema was evident and remained substantial after 4 years in Taiwan. Continuous surveillance is important to monitor the emergence of other pathogens including non-PCV serotypes and M. pneumoniae.

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.

Background: Clostridium difficile infection (CDI) is increasing in children. We aimed to compare the clinical characteristics between CDI and colonization and to identify the risk factors for severe diseases of CDI in children. Method: We retrospectively reviewed 124 children (1–18 years old) from 2011 to 2018. CDI was defined as diarrhea (≥3 loose stool in the past 24 h) with confirmed toxigenic strain. Colonization was defined as presence of C. difficile without clinical symptoms. Severe diseases included ileus, acute kidney injury, gastrointestinal bleeding or mortality. Patients younger than 1 year old and coinfections with other enteric pathogens were excluded. Results: Among 124 patients with C. difficile identified, 49 of them fulfilled CDI definition and 75 had C. difficile colonization. Children with CDI were more likely to present with watery (74% vs. 1%, p

Background/Purpose: Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods: We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results: Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion: COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.

Japanese encephalitis (JE) is a mosquito-borne viral infection which is prevalent in Taiwan. The virus circulates in an enzootic cycle in pigs which serve as amplifying hosts. Outbreaks typically occur during summer. A universal vaccination program using 4-shot mouse brain-derived inactivated vaccine has successfully controlled JE epidemics in Taiwan since 1968. More than 90% of JE cases in recent years were older than 20 years in Taiwan. Because of several drawbacks, mouse brain-derived vaccine has been replaced by newer generation JE vaccines, including inactivated Vero cell-derived vaccine and live chimeric vaccine. The present article describes the recommendations in Taiwan for the use of new JE vaccines and the schedules for shifting between different JE vaccines. Key Words: epidemiology, immunization schedule, Japanese encephalitis, vaccination

Abstract Background Nasal colonization of Staphylococcus aureus is a risk factor for the pathogen transmission and the development of infections. Limited information is available on the prevalence and molecular characteristics of S. aureus colonization in pediatric intensive care unit (ICU) patients. Methods A cross-sectional, island-wide study was conducted in 2011. Nasal swabs were collected from pediatric ICU patients at six tertiary hospitals in Taiwan. Results Of 114 patients enrolled in total, nasal colonization of S. arueus was detected in 30 (26.3%) of them, among whom 20 (17.5%) with methicillin-resistant S. arueus (MRSA). The ST59/SCCmec IV and V clones were most common and accounted for 45% of MRSA isolates, followed by ST239/SCCmec III (25%) and ST45/SCCmec IV (20%) clones. Three ST59 MRSA isolates carried the Panton-Valentine Leukocidin genes. Conclusions The results indicated a high prevalence of S. arueus and MRSA nasal colonization among pediatric ICU patients in Taiwan. Identification of epidemic clones warrants the implement of infection control measures to reduce colonization and prevent the dissemination of MRSA in hospitals.

Enterovirus D68 was first identified in 1962 and caused a worldwide outbreak starting from the North America in 2014. Enterovirus D68 has been in continuous circulation among many countries recently, including Taiwan. Reports also reveal high seroprevalence, which indicates that the disease burden of enterovirus D68 may be underestimated via viral culture or polymerase chain reaction results. Although most infected cases have mild respiratory illness, severe complications including acute flaccid myelitis and acute respiratory distress syndrome have also been reported. In the position of an emerging pathogen, enterovirus D68 poses a threat to public health and may cause devastating diseases. Diverse severity of neurological sequelae remains inevitable among acute flaccid myelitis patients, but no curable treatment is available currently. According to the management suggestions of the American Centers of Disease Control, uses of corticosteroids and plasmapheresis are either preferred or avoided and intravenous immunoglobulin also has no clear indication in the treatment for acute flaccid myelitis. In this review article, we provide information about the epidemiology, clinical recognition and treatment strategy of enterovirus D68. Better understanding of this disease is the foothold for advanced investigation and monitoring in the future. Key Words: acute flaccid myelitis, enterovirus D68, respiratory illness

BackgroundTimely decision-making regarding intensive care unit (ICU) admission for children with pneumonia is crucial for a better prognosis. Despite attempts to establish a guideline or triage system for evaluating ICU care needs, no clinically applicable paradigm is available. ObjectiveThe aim of this study was to develop machine learning (ML) algorithms to predict ICU care needs for pediatric pneumonia patients within 24 hours of admission, evaluate their performance, and identify clinical indices for making decisions for pediatric pneumonia patients. MethodsPneumonia patients admitted to National Taiwan University Hospital from January 2010 to December 2019 aged under 18 years were enrolled. Their underlying diseases, clinical manifestations, and laboratory data at admission were collected. The outcome of interest was ICU transfer within 24 hours of hospitalization. We compared clinically relevant features between early ICU transfer patients and patients without ICU care. ML algorithms were developed to predict ICU admission. The performance of the algorithms was evaluated using sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and average precision. The relative feature importance of the best-performing algorithm was compared with physician-rated feature importance for explainability. ResultsA total of 8464 pediatric hospitalizations due to pneumonia were recorded, and 1166 (1166/8464, 13.8%) hospitalized patients were transferred to the ICU within 24 hours. Early ICU transfer patients were younger (P

Background: Influenza is a major cause of acute respiratory infection burden worldwide, leading to many hospitalizations. An annual influenza vaccine is believed to be the best way to prevent influenza-related illnesses. We focused on the efficacies of other possible preventive measures such as increasing sun exposure time and dietary supplements to prevent these illnesses. Methods: We conducted a matched-pair case–control study along with the Taiwan Pediatric Infectious Disease Alliance. We included influenza-related hospitalized patients with age ranging from 6 months to 5 years during the 2012–2013, 2013–2014, 2014–2015, and 2015–2016 influenza seasons. The controls were comparable to cases in age, sex, and residential area and had no influenza-related hospitalization records in the same season. We extracted data from vaccination histories and got the patients’ guardians to complete questionnaires. Data were analyzed using conditional logistic regression. Results: We enrolled 1514 children (421 influenza-infected cases and 1093 controls) in the study. We found seasonal influenza vaccination to be an independent protective factor against hospitalizations owing to influenza [p 7 h/week had a significantly lower risk of influenza-related hospitalizations than those with the mean sun exposure time of ≤7 h/week (p 7 h of sun exposure/week may also be associated with lower risk of influenza-related hospitalizations in children. Keywords: Influenza, Vaccine effectiveness, Hospitalization, Sun exposure time

Background: Pneumocystis jiroveci pneumonia (PJP) is a severe and lethal opportunistic infection in the immunocompromised patients. As the increasing usage of immunosuppressants, the incidence of non-HIV related PJP has increased in recent years. Still, there is little research regarding children with PJP. The aim of this study is to understand PJP more among pediatric population. Methods: We reviewed the medical records of the patients with PJP in National Taiwan University Hospital from 2014 to 2017. Diagnosis was made if the patient met all of the criteria: presence of relevant pulmonary symptoms and signs, pulmonary infiltrates on images, detection of Pneumocystis jiroveci from respiratory specimens via polymerase chain reaction (PCR), and received antibiotics for PJP. Results: Twenty children and 132 adults were enrolled in this study. The most common underlying diseases among children included malignancy (40%), post-transplantation (30%), and primary immunodeficiency (20%). The major underlying diseases in adults included malignancy (36%), HIV with acquired immunodeficiency syndrome (AIDS) (31%), and autoimmune diseases (24%). There is no significant difference in the clinical manifestations, mortality, and complication between children and adults, but children tended to have less chance of using alternative antibiotics, methylprednisolone and inhaled nitric oxide (NO). The chance of concomitant cytomegalovirus disease was also significantly lower in pediatric patients. Conclusion: No significant difference was found in the clinical manifestations, mortality, and complication between children and adults, but children tended to have lesser chance of using alternative antibiotics, methylprednisolone and inhaled NO. The chance of associated cytomegalovirus (CMV) disease was also significantly lower in children. Keywords: Opportunistic infection, Pediatric, Pneumocystis jiroveci pneumonia

Background/purpose(s): Enterovirus D68(EV-D68) is an emerging disease that affects mostly children. There have been few relevant investigations to clarify transmission and seroprevalence within daycares and kindergartens. Methods: This prospective cohort study investigated respiratory viral transmission among preschool children in a public kindergarten in Taipei City of Taiwan between September 2006 and June 2008. After children were enrolled, daily monitoring of illness and regular biweekly physical examinations were performed. We performed viral isolation to detect acute EV-D68 infection and neutralization tests to detect specific EV-D68 antibodies and to measure the seroprevalence and seroconversion rates. Results: Among 190 kindergarten attendees aged between two to five years old, nine children had acute EV-D68 infection in September 2007. The clinical manifestations included pharyngitis, cough and other unspecified upper respiratory tract infection. None of the infected children had acute flaccid paralysis or severe respiratory illness. The phylogenetic tree of partial viral protein 3 and viral protein 1 was clustered in clade A1. The EV-D68 seropositive rate increased from 19% (25/130) at the beginning to 67% (83/124) at the end of the study. The seroconversion rate of 49 children with initial seronegative and paired sera was 73% (36/49). Conclusions: A high seroconversion rate (73%) for EV-D68 was found among kindergarten attendees, which indicates preschool-aged children are highly susceptible to EV-D68 infection and that the disease burden may be extremely underestimated. Once EV-D 68 circulates, preventive measures may be advocated, especially within kindergartens or daycares, to reduce transmission and subsequent development of severe cases. Keywords: Enterovirus D68, Kindergarten attendees, Manifestation, Seroconversion

Background: During one week in September, one index case, followed by two cases of rotavirus gastroenteritis infection, was identified in a neonate intermediate care unit of a tertiary teaching children's hospital. An outbreak investigation was launched to clarify the possible infection source and to stop the spread of infection. Methods: Cohort care and environmental disinfection were immediately implemented. We screened rotavirus in all the unit neonates' stool samples as well as environmental swab samples. The precautionary measures with regard to hand hygiene and contact isolation taken by healthcare providers and family members were re-examined. Results: The fourth case was identified 5 days after commencement of the outbreak investigation. There were total 39 contacts, including 6 neonates, 8 family members, and 25 healthcare providers. Nineteen stool samples collected from other neonates in the units revealed one positive case (the fourth case). However, one sample taken from the computer keyboard and mouse in the ward was also positive. The observation of hygiene precautions and the use of isolation gowns by healthcare workers were found to be inadequate. Following the intensification of infection control measures, no further cases of infection were reported. Conclusions: Hand hygiene and an intensive isolation strategy remained the most critical precautions for preventing an outbreak of healthcare-associated viral gastroenteritis in the neonate care unit. Keywords: Rotavirus, Outbreak, Neonatal care unit, Infection control

Background/purpose: Pertussis incidence markedly decreased due to universal vaccination, but outbreaks had been noted worldwide in recent decade. This study was conducted to know the epidemiology of pertussis and its impact on infants in Taiwan. Methods: Epidemiologic parameters for confirmed pertussis cases were collected from the Taiwan Centers for Disease Control. The incidence of each age group over years was calculated using population data. We also did retrospective reviews of laboratory-confirmed pertussis cases in NTUH to analyze clinical characteristics and disease severity. Results: A total of 668 confirmed pertussis cases were obtained from the Taiwan CDC open database between 2003 and 2017. There was higher incidence during the period 2009–2015, with a mean incidence of 0.27 cases per 100,000 population, about 2-fold increase compared with mean incidence of 0.12 cases per 100,000 population during the period 2003–2008. Infants accounted for the highest proportion of all cases (49.8%), with mean incidence of 16.1 cases per 100,000 people per year during 2009–2015, and a trend of increase was found from 2003 to 2015. In NTUH, a total of 17 laboratory-confirmed pertussis cases were diagnosed during 2012–2016, and 14 cases were young infants. Among them, 9 infants had been admitted to intensive care unit and 2 infant needed invasive ventilator support. Conclusion: There was a resurgence of pertussis during 2009–2015 and it had significant impact on infants. Young infants with pertussis may be severe and need intensive care, so preventive strategy may be advocated for them. Keywords: Epidemiology, Infant, Maternal immunization, Pertussis

Background/Purpose: The clinical presentations of parvovirus B19 in patients with underlying diseases have greater diversity than previously healthy patients. We retrospectively identified patients with polymerase chain reaction (PCR)-confirmed parvovirus B19 infection in attempt to describe its clinical features especially in these populations. Methods: From 2009 to 2018, patients with real-time PCR-confirmed parvovirus B19 infection were collected. Comparisons were done between previously healthy patients and patients with preexisting diseases, as well as patients with high (>5.5 × 105 copies/mL sera) and low viral loads. Results: Parvovirus B19 DNA was detected in 31 patients. Fourteen (45%) patients had underlying diseases, including six (19%) with immunologic diseases, five (16%) with hematologic diseases, and three (10%) with cardiopulmonary diseases. Only seven (23%) patients received an initial impression of erythema infectiosum prior to positive PCR. A higher proportion of patients with underlying diseases presented with fatigue and pallor, and suffered from tachycardia and hepatosplenomegaly compared to previously healthy patients. Among patients with a high viral load, a substantial proportion were of older age, suffered fatigue, and anemia. There was a trend of patients with immunologic comorbidity having a higher viral load. Conclusion: The classical parvovirus B19 manifestations were less frequently observed in patients with a preexisting disease compared with previously healthy patients. Depending on host factors, the symptoms of parvovirus B19 infection can be multifaceted. Keywords: Human parvovirus B19, Erythema infectiosum, Aplastic crisis, Pure red-cell aplasia

Abstract 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.

Background: Adenovirus infections are very common in children and sometimes fatal. Immune responses and hypercytokinemia are related to disease severity in patients with adenovirus infection. Understanding of viral replication and immune responses could help elucidate the immunopathogenesis of severe adenovirus infections. Methods: Polarized human airway epithelial cells (hAECs) were set up to mimic human airway, and we conducted high (1 the multiplicity of infection, MOI) and low dosage (0.5 MOI) of wild-type adenovirus serotype 3 infection in hAECs from both apical (AP) and basolateral (BL) compartments, compared the viral replication kinetics and measured 25 cytokine and 9 chemokine levels by multiplex immunoassay to evaluate the host immune response. Results: Virus titer was the highest in the apical compartment in low dose apical infection. BL infection showed a relative steady viral titer in different doses and infection sites. Responses of several cytokines such as IL-1RA, IL-21 and all of the chemokines were found after adenovirus infection. Besides, the responses detected in the BL compartment were generally higher than those in the apical compartment, especially IL-1RA, IL-21, GM-CSF, GRO-α, SDF-1α and IL-8. Conclusion: During the infections of hAECs by adenovirus, higher viral replication was found in the apical compartment but cytokine and chemokine responses were higher in the basolateral compartment. This indicated viral entrance and replication occurred more in the apical part and major innate response took place in the basolateral part, which may make adenovirus infect human airway efficiently and cause different degree of severity. Keywords: Adenovirus, Human airway epithelial cells, Cytokine, Chemokine

Background: Mycoplasma pneumoniae is a common pathogen for pneumonia in children, especially in the post-pneumococcal conjugate vaccination era. Though self-limited disease was found in the majority of the patients, severe diseases occurred occasionally. The emergence of macrolide resistance was reported worldwide. It is important to delineate whether macrolide resistance or delayed treatment affects outcome. Methods: We retrospectively collected pediatric patients with M. pneumoniae infection confirmed by positive PCR in a tertiary medical center in Taiwan from 2010 to 2017. Patients’ clinical characteristics, bacterial load, macrolide resistance and treatment outcome were analyzed. Results: Among 471 children with positive M. pneumoniae PCR, 95% were diagnosed with pneumonia. Seventeen percent of patients had extrapulmonary complications, and 1.5% had respiratory failure. Delayed treatment was associated with prolonged fever after appropriate treatment, fulminant disease, and extrapulmonary manifestations (p

Background/purposes: Human adenovirus (HAdV) infection is prevalent and has an important clinical impact on children. We aim to investigate the molecular epidemiology of HAdV infection and discover the correlations between clinical features and HAdV species in an HAdV outbreak of 2014. Methods: This is a retrospective study, enrolling patients under 19 years of age with HAdV infection at the National Taiwan University Hospital in 2014. We gathered the demographic and clinical data, carried out molecular typing and constructed a phylogenetic tree. Statistical analyses were performed in terms of HAdV species and hospitalization. Results: A total of 531 patients with HAdV infection were identified. HAdV-B accounted for the largest proportion (n = 387, 73%). On average, patients infected with HAdV-E were oldest, whereas those with HAdV-C infection were youngest (p

The molecular chaperon MRJ (DNAJB6) exhibits two splice isoforms that have different roles in human viral infection, but the regulatory mechanism of MRJ isoform expression is yet unclear. In this study, we show that reduction of the polyadenylation factor CstF64 was correlated with the increase of the MRJ large isoform (MRJ-L) in human macrophages and elucidate the mechanism underlying CstF64-modulated MRJ isoform expression. Moreover, we exploited an antisense strategy targeting MRJ-L for virus replication. A morpholino oligonucleotide complementary to the 5′ splice site of MRJ intron 8 downregulated MRJ-L expression and suppressed the replication of not only HIV-1 but also respiratory syncytial virus (RSV). We demonstrated that downregulation of the MRJ-L level reduced HIV-1 replication as well as the subgenomic mRNA and viral production of RSV. The present findings that two human health-threatening viruses take advantage of MRJ-L for infection suggest MRJ-L as a potential target for broad-spectrum antiviral strategy. Keywords: MRJ, DNAJB6, splicing, polyadenylation, CstF64, RSV, HIV-1

BACKGROUND:Enterovirus D68 (EV-D68) was discovered in 1962 and has unique characteristics compared to the characteristics of other enteroviruses. There were few documented cases before the epidemic in the United States in 2014. The Taiwan Centers for Diseases Control also confirmed that EV-D68 has been endemic, and some cases of acute flaccid myelitis were reported in Taiwan. To understand the current EV-D68 serostatus, we performed an EV-D68 seroepidemiology study in Taiwan in 2017. METHODS:After informed consent was obtained, we enrolled preschool children, 6- to 15-year-old students and 16- to 49-year-old people. The participants underwent a questionnaire investigation and blood sampling to measure the EV-D68 neutralization antibody. RESULTS:In total, 920 subjects were enrolled from the northern, central, southern and eastern parts of Taiwan with a male-to-female ratio of 1.03. The EV-D68 seropositive rate was 32% (26/82) in infants, 18% (27/153) in 1-year-old children, 43% (36/83) in 2-year-old children, 60% (94/156) in 3- to 5-year-old children, 89% (108/122) in 6- to 11-year-old primary school students, 98% (118/121) in 12- to 15-year-old high school students, 100% (122/122) in 16- to 49-year-old women and 100% (81/81) in 16- to 49-year-old males in 2017. Among preschool children, EV-D68 seropositivity was related to age (p for trend

Objectives: Enterovirus 71 (EV71) may cause neurological and fatal cases. EV71 3C plays an important role on viral replication and possess proteolysis activity. To delineate pathogenesis of EV71 virulence, we studied EV71 3C genetics, protease activity and correlated the results with clinical severity. Methods: EV71 cases were collected; 3C of EV71 was sequenced and linked with clinical severity. 3C protease activity, viral replication rates of EV71 infectious clones with different 3C and 3C interaction with host proteins were analyzed. Results: The polymorphisms of EV71 3C at the 79th amino acid were associated with clinical severity. About 26% (62/234) patients infected by EV71 with wild-type 3C (T79) had neurological involvement but 78% (25/32) patients infected by EV71 with mutant 3C (T79V) did (p

Background: Refractory septic shock is the leading cause of mortality in children. There is limited evidence to support extracorporeal membrane oxygenation (ECMO) use in pediatric septic shock. We described the etiology and outcomes of septic patients in our institution and attempted to find predictive factors. Methods: We retrospectively reviewed 55 pediatric patients with septic shock who required ECMO support in a tertiary medical center from 2008 to 2015. Septic shock was defined as culture proved or clinical suspected sepsis with hypotension or end-organ hypoperfusion. ECMO would be applied when pediatric advanced life support steps were performed thoroughly without clinical response. Patient's demographics, laboratory parameters before and after ECMO, and outcomes were analyzed. Results: Among 55 children with ECMO support, 31% of them survived on discharge. For 25 immunocompromised patients, causal pathogens were found in 17 patients: 7 due to bacteremia, 9 with preexisting virus infections and one with invasive fungal infection. Among 30 previously healthy patients, causal pathogens were found in 18 patients: 10 due to bacteremia (the most common was pneumococcus), 7 with preexisting virus infections including influenza (n = 4), adenovirus (n = 2), RSV, and 1 patient had mixed virus and bacterial infections. Predictive factors associated with death were arterial blood gas pH, CO2 and Glasgow Coma Scale (p

Objective: The use of corticosteroid in Kawasaki disease (KD) remains controversial among current guidelines. The objective of this study is to summarize the effectiveness and safety of corticosteroid to prevent coronary arterial lesions in Kawasaki disease, both as initial and rescue therapy. Methods: The Medline, EMBASE, Google scholar, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov, and Japanese Institutional Repositories Online were searched for studies up to 31 March 2017. Studies that compared incidence of coronary artery lesions between regimens with corticosteroid and regimen without it in a well-defined controlled group were included. The incidence of coronary artery lesion was analyzed by meta-analysis. Results: Nineteen studies published between 1999 and 2016 fulfilled eligibility criteria. There were 3591 patients included for analysis. There was a significant reduction in incidence of coronary artery lesions with usage of corticosteroid with a pooled odds ratio of 0.72 (95% CI 0.57–0.92; p = 0.01) than that without usage of corticosteroid. In general, a greater effect was seen in the patient received corticosteroid as initial and adjuvant therapy with intravenous immune globulin (pooled odds ratio 0.39, 95% CI 0.21–0.73, p = 0.007) than those who received corticosteroid as rescue therapy. The risk reduction was statistically significant in Japanese groups (OR 0.56, 95% CI 0.42–0.75 in fixed effects model) but not significant in non-Japanese groups (OR 1.45, 95% CI 0.91–2.30 in fixed effects model). Conclusions: We demonstrated an overall reduction in incidence of coronary artery lesions with the use of corticosteroid as initial and adjuvant treatment for Kawasaki disease.

Background: Invasive fungal infection (IFI) causes significant morbidity and mortality in patients with hematological malignancies, especially those with acute myeloid leukemia (AML), recurrent acute leukemia, high-risk acute lymphoblastic leukemia, and after allogeneic hematopoietic stem cell transplantation. The study aimed to investigate the clinical characteristics and outcome of IFIs in pediatric AML patients in a medical center in Taiwan. Methods: We performed retrospective chart reviews. We enrolled pediatric AML patients who were admitted to National Taiwan University Hospital between January 2005 and December 2014. IFI was defined according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group 2008 consensus criteria. Results: In total, 78 patients were included for analysis. Twenty two episodes of IFIs were identified in 16 patients. The incidence for IFIs was 20.5% (16/78), and no specific trend of increase or decrease was observed through the study period (p=0.374). Candida species caused the majority (59.1%) of IFIs. Prolonged neutropenia and elevated alanine aminotransferase and creatinine values were factors associated with IFIs (p

Background: In Taiwan, the age group with the greatest incidence of invasive pneumococcal disease is 2–5 years of age, which is different from other countries. This study was conducted to identify risk factors and different 13-valent pneumococcal conjugate vaccine (PCV13) schedules associated with vaccine-type invasive pneumococcal pneumonia (IPP) despite prior vaccination. Methods: A case–control study was conducted prospectively between August 2012 and December 2015 at five participating medical centers. The study enrolled children