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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

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: 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: 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.

Background/Purpose: Invasive candidiasis is a severe infectious disease that could lead to mortality in critically ill children. Methods: We collected data regarding demographics, underlying diseases, predisposing factors, outcomes for pediatric patients with candidemia at a medical centre in Taiwan from 2011 to 2017. Results: Fifty-eight patients with 60 candidemia episodes were diagnosed. The 3 most common species were Candida albicans (42%), Candida parapsilosis (25%) and Candida tropicalis (23%). C. parapsilosis predominantly infected infants and neonates (median age: 0.8 years, range: 0.1–14.5). Cases with C. tropicalis had significantly higher rates of multidrug resistance (p = 0.011) and disseminated candidiasis (p = 0.025) compared with other cases. The all-cause mortality rate was 43%, and the candidemia-related mortality rate was 29%. Pediatric sequential organ failure assessment score >8 [adjusted odds ratio (aOR) 66.2, 95% CI 4.03–1088.5] and posaconazole resistance (aOR 33.57, 95% CI 1.61–700.3) were the most significant risk factors associated with candidemia-related mortality, whereas treatment with effective antifungal agents within 48 h (aOR 0.07, 95% CI 0.01–0.9) was the only significant protective factor. Conclusion: Candidemia-related mortality was related to azole resistance; therefore, empirical therapy with echinocandin or amphotericin B is recommended pending species and susceptibility results.

Background: Since the global use of the pneumococcal conjugate vaccine, Mycoplasma pneumoniae (MP) has become the most common bacterial cause of lower respiratory tract infections among children. Monitoring the changing epidemiology and antimicrobial resistance rates of this organism is important for MP clinical management. Methods: This study characterizes key features of MP during the 2019–2020 epidemic in children in Taiwan. The cohort included all hospitalized children under 18 years of age with polymerase chain reaction (PCR)-confirmed community-acquired mycoplasma pneumonia (CAMP) in southern Taiwan. Macrolide resistance was identified by mutations in domain V of MP 23S rRNA. Severe disease referred to symptoms warranting oxygen therapy, septic shock, or intensive care unit admission. Results: Among 495 LRTI patients, 195 (39.4%) had CAMP, of which 106 (54.4%) had concurrent serological evidence of MP infection. The diagnostic sensitivity of IgM in the acute phase was 65.6%. CAMP case numbers were highest from July 2019 to January 2020. The most common clinical presentations of CAMP were fever (99.0%), cough (99.0%), and coryza (31.8%). Despite a high rate of macrolide resistance (88.1%), macrolide-resistant MP (MRMP) did not differ from macrolide-sensitive MP (MSMP) in clinical course or severity. Delayed administration of effective antimicrobial treatment was also associated with severe disease (p

Abstracts: Despite the rising natural and vaccines mediated immunity, several countries have experienced a resurgence of the Coronavirus disease of 2019 (COVID-19) due to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. From Alpha to Omicron, the variants of concern (VOC) have evolved several spike protein mutations that may have an impact on virus characteristics, such as transmissibility and antigenicity. In this review, we describe the evolution of SARS-CoV-2, summarize current knowledge of epidemiological and clinical features of the variants, and discuss the response strategies in terms of vaccines to reduce the burden of COVID-19.

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

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

Background: Norovirus is a common acute gastroenteritis (AGE) pathogen across all age groups worldwide, which is difficult to differentiate from other pathogens. This study aimed to understand the clinical characteristics and risk factors of norovirus gastroenteritis among children in Taiwan. Methods: A prospective AGE surveillance study was conducted in children aged ≤5 years who were hospitalized in 10 major hospitals in Taiwan between 2014 and 2017. The non-AGE control group included healthy children who were matched based on age, gender, season, and geographic area. Results: Overall, 674 norovirus gastroenteritis patients were enrolled. Fever (p

Purpose: This study aimed to compare the safety and efficacy of clarithromycin-naproxen-oseltamivir combination therapy to that of oseltamivir therapy alone in hospitalized pediatric influenza patients. Methods: This prospective, single-blind study included children aged 1–18 years hospitalized with influenza, in MacKay Children's Hospital, Taiwan, between December 2017 and December 2019. The primary outcomes were the time to defervescence and decrease of the Pediatric Respiratory Severity Score (PRESS) during hospitalization. The secondary outcomes were serial changes in virus titers, measured using real-time polymerase chain reaction. Results: Fifty-four patients were enrolled (28 in the control group and 26 in the combination group) in total. There were no differences in the patients’ baseline characteristics between the groups. The time to defervescence was significantly shorter in the combination group than the oseltamivir group (13.2 h vs. 32.1 h, p = 0.002). The decrease in the virus titer from days 1–3 (log Δ13) was more pronounced in the combination group than the oseltamivir group. (39% vs. 19%, p = 0.001). There were no differences in adverse effects such as vomiting, diarrhea, and abdominal pain during the study or within 30 days after antiviral therapy. Conclusion: The clarithromycin-naproxen-oseltamivir combination group experienced a more rapid defervescence and a more rapid decline of influenza virus titer than the group treated with oseltamivir alone. Further consideration should be given to whether the overall benefits of combination therapy in hospitalized pediatric influenza patients outweigh the risks.

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.

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/purpose: To date, molecular typing studies on Mycoplasma pneumoniae are limited. We evaluated the molecular types of Mycoplasma pneumoniae in pediatric patients in Taiwan in 2016. Methods: We used real-time quantitative PCR on respiratory specimens to identify M. pneumoniae in children with community-acquired pneumonia. The domain V of their 23S rRNA were sequenced for detection of macrolide-resistant point mutations. Molecular typing with multiple locus variable-number tandem repeat analysis (MLVA) was done for both macrolide-susceptible and -resistance M. pneumoniae samples. Results: M. pneumoniae was detected in 22% (180/826) respiratory samples during the study period. Among all M. pneumoniae-positive samples, 24% (43/180) had harbored macrolide-resistant genotypes, and 86% (37/43) of them were A2063G mutation. Forty-two macrolide-resistant strains and 20 randomly selected macrolide-susceptible strains underwent MLVA profiling. MLVA 4-5-7-2 was the most frequent type (32/62, 52%), followed by 4-5-7-3 (17/62, 27%) and 1-5-6-2 (9/62, 15%). There was a strong association between MLVA 4-5-7-2 and macrolide resistance (p < 0.001). In contrast, M 4-5-7-3 and 1-5-6-2 were related to macrolide susceptibility (p < 0.001, and p = 0.025, respectively). Conclusion: Macrolide resistance was relatively low (24%) in this age group in 2016 in Taiwan, and A2063G was the dominant point mutation. MLVA 4-5-7-2 was associated with macrolide resistance.

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: 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

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: As COVID-19 has become a pandemic emerging infectious disease it is important to examine whether there was a spatiotemporal clustering phenomenon in the globe during the rapid spread after the first outbreak reported from southern China. Materials and methods: The open data on the number of COVID-19 cases reported at daily basis form the globe were used to assess the evolution of outbreaks with international air link on the same latitude and also including Taiwan. The dynamic Susceptible-Infected-Recovered model was used to evaluate continental transmission from December 2019 to March 2020 before the declaration of COVID-19 pandemic with basic reproductive number and effective reproductive number before and after containment measurements. Results: For the initial COVID-19 outbreak in China, the estimated reproductive number was reduced from 2.84 during the overwhelming outbreaks in early January to 0.43 after the strict lockdown policy. It is very surprising to find there were three countries (including South Korea, Iran, and Italy) and the Washington state of the USA on the 38° North Latitude involved with large-scale community-acquired outbreaks since the first imported COVID-19 cases from China. The propagation of continental transmission was augmented from hotspot to hotspot with higher reproductive number immediately before the declaration of pandemic. By contrast, there was not any large community-acquired outbreak in Taiwan. Conclusion: The propagated spatiotemporal transmission from China to other hotspots may explain the emerging pandemic that can only be exempted by timely border control and preparedness of containment measurements according to Taiwan experience.

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

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

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

Background: Streptococcus pneumoniae serotype 19A ST320, a highly multiresistant and virulent clone, has emerged as a common pathogen causing acute otitis media (AOM) in children. Methods: Patients aged 0–18 years with AOM who presented at Mackay Memorial Hospital, Taipei, Taiwan were prospectively enrolled between December 1, 2009, and November 30, 2012. For each patient, a specimen of middle-ear fluid was obtained and cultured. S. pneumoniae isolates were tested by serotyping, antibiotic-resistance profiling, and multilocus sequence typing. Demographic characteristics and clinical history of patients with pneumococcal AOM were recorded. Results: Pneumococcal AOM was observed in 108 (24.8%) of 436 episodes. One hundred and four isolates of S. pneumoniae were available for study. The most common serotypes were 19A (67 isolates, 64.4%), followed by 19F (16 isolates, 15.4%), and 3 (7 isolates, 6.7%). Among the 85 sequence-typed isolates, Serotype 19A ST320 (50, 58.8%) was the most frequent. Children with AOM caused by Serotype 19A ST320 were younger (33.9 ± 21.4 months vs. 46.7 ± 35.9 months, p = 0.04) and had a higher rate of spontaneous rupture of the tympanic membrane (64.0% vs. 40%, p = 0.05) than those caused by isolates of other sequence types. Serotype 19A ST320 caused 90% of AOM episodes in children aged ≤ 12 months and had had higher resistance rates to penicillin according to meningeal breakpoints (p = 0.011), amoxicillin (p < 0.001) and trimethoprim/sulfamethoxazol (p < 0.001). Conclusions: It is better to use pneumococcal conjugate vaccine effective against Serotype 19A in early infancy to prevent the first and subsequent episodes of AOM in children in Taiwan.

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

Kindergarteners frequently encounter various infectious diseases, so surveillance of viral infectious diseases would provide information for their health promotion. Methods: We enrolled kindergarten attendees, age 2–5 years, during the academic years of 2006 and 2007 in a Taipei City kindergarten. Daily monitoring of illness and regular biweekly physical examinations were undertaken. Multiple infections were defined as one child having two or more laboratory-confirmed viral infections with different viruses or different serotypes during one academic year. Results: The overall laboratory-confirmed incidence rate of respiratory viral infection was 239 per 100 person–years in the 2006 academic year and 136 per 100 person–years in the 2007 academic year. The attack rate for seasonal influenza was 17% in the 2006 academic year and 27% in the 2007 academic year. Boys and children with allergies had significantly higher risks to get multiple viral infections [odds ratio (OR) 1.81, 95% confidence interval (CI) 1.20–2.75; OR 1.56, 95% CI 1.00–2.39, respectively]. Boys also tended to get enterovirus infections (OR 1.56, 95% CI 1.02–2.38) while children with allergies tended to acquire adenovirus infections (OR 1.71, 95% CI 1.12–2.66). Conclusion: Boys and children with allergies were more susceptible to multiple viral infections, so they should be more cautious about viral infections.

Background: Acute gastroenteritis (AGE) can be caused by a wide array of pathogens, including bacteria, viruses, and parasites. A prospective study to investigate the epidemiology and clinical presentation in young children hospitalized with AGE was conducted in a medical center in southern Taiwan. Methods: Patients aged less than 5 years who was hospitalized due to AGE in National Cheng Kung University Hospital were enrolled from July 2014 to June 2016. The demographic information, clinical features and laboratory data were collected by chart reviews, and stool samples were sent to Centers of Disease Control, Taiwan (Taiwan CDC) for a panel of pathogen identification consisting of two viruses, nine bacteria, and five parasites. Results: Totally 441 patients were enrolled in this study. Salmonella spp. was the leading cause of disease (21.8%), followed by norovirus (17.0%), Clostridium difficile (9.5%), and rotavirus (9.3%). Norovirus identification rate was the highest among patients less than 6 months of age, while Salmonella was highest among patients between 2 and 3 years old. Patients with Salmonella infection frequently presented with fever, lethargy, bloody stool, and elevated serum level of C-reactive protein (CRP); norovirus and rotavirus infection frequently presented with vomiting. Salmonella gastroenteritis also resulted in longer hospitalization and more frequent antibiotics administration. C. difficile could be isolated from both gastroenteritis patients and control children. Conclusion: Salmonella spp. was the most common pathogen of AGE in hospitalized children in southern Taiwan during 2014â2016, followed by norovirus and rotavirus. Further monitoring of epidemiology characteristics among cardinal pathogens of pediatric gastroenteritis is necessary. Keywords: Acute gastroenteritis, Children, Epidemiology, Taiwan

Background: Cytomegalovirus (CMV) is a major pathogen causing significant mortality and morbidity in immunocompromised hosts. It is important to find risk factors associated with CMV viremia and its outcome. Methods: We investigated the incidence, time of onset, risk factors for CMV viremia, and characteristics of CMV diseases in 57 pediatric patients receiving hematopoietic stem cell transplantation (HSCT). Between August 2011 and March 2014, cases of pediatric HSCT patients at the National Taiwan University Children's Hospital were reviewed. Viremia was identified by plasma CMV real-time polymerase chain reaction (RT-PCR) assay. Results: Eighteen (32%) of the 57 patients developed CMV viremia at a median of 23 days post-HSCT (range −3 to +721 days). Eighty-nine percent (16/18) of CMV viremia occurred within 100 days posttransplantation. Four patients finally had CMV diseases (1 with CMV colitis and 3 with CMV pneumonitis) and one patient died of CMV pneumonitis complicated with pulmonary hemorrhage and sepsis. Significant risk factors associated with CMV viremia via univariate analysis include older age (p = 0.03), leukemic patients [odds ratio (OR): 5.2, 95% confidence interval (CI): 1.52∼17.7, p = 0.008), allogeneic HSCT (OR: 14.57, 95% CI: 1.76∼120.5, p = 0.002), antithymoglobulin (ATG) use before transplantation (OR: 5.09, 95% CI: 1.52∼16.9, p = 0.007), graft-versus-host disease (GvHD) (OR: 10.1, 95% CI: 2.7∼38.7, p

The incidence of congenital heart disease (CHD) and severe CHD is 13.08 and 1.51/1000 live births, respectively, in Taiwan, which has had national health insurance since 1995 and child health indices similar to those in the US. This study sought to further elucidate the fatality of CHD patients and their survival from a national database. Methods: From the national health insurance database 2000–2010, we retrieved data from CHD patients who were diagnosed at age

Kawasaki disease (KD) is a disease of unknown cause and the causative agent is most likely to be infectious in nature. To investigate the household transmission pattern of infectious illness and etiology, we thus initiated a prospective case and household study. Methods: We enrolled KD cases and their household members from February 2004 to September 2008. The KD cases and their household members accepted questionnaire-based interviews of the contact history, signs of infection, and symptoms to check whether clusters of infectious illness occurred. Results: A total of 142 KD cases and 561 household members were enrolled. Among the 142 KD cases, 136 cases (96%) were typical KD, and six (4%) were atypical KD. Of the 561 household members, 17% were siblings, 46% were parents, 18% were grandparents, and the others were cousins or babysitters. Prior to the onset of their KD illness, 66% (94/142) KD cases had contact with ill household members. On the same day of the onset of KD cases' illness, 4% (6/142) KD cases had household members with illness. After KD cases' disease onset, 70% (100/142) KD cases had at least one other family member with illness. Overall, 61% (343/561) of all the household members had acute infectious illness during KD cases' acute stage, and 92% (130/142) of the families had clusters of infectious illness. Conclusion: A total of 66% KD cases had positive contact with ill household members prior to their disease onset and 92% of families had clusters of infectious illness, so KD is strongly associated with infections.