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Background: The regional respiratory syncytial virus (RSV) outbreak in southern Taiwan in late 2020 followed the surge of RSV cases in the national surveillance data and displayed distinct clinical features. This study investigated RSV epidemiology in the most recent five years and compared the clinical manifestations of this outbreak with non-outbreak period., Methods: Medical records of RSV-infected children at the National Cheng Kung University Hospital from January 2016 to December 2020 were retrospectively retrieved from hospital-based electronic medical database. Cases of RSV infection were identified by RSV antigen positive and/or RSV isolated from respiratory specimens. The demographic, clinical presentations, and laboratory data were recorded. The RSV isolates in 2020 was sequenced for phylogenetic analysis., Results: Overall, 442 RSV-infected cases were retrieved and 42.1% (186 cases) clustered in late 2020. The 2020 outbreak started in September, peaked in November, and lasted for 3 months. 2020 RSV-infected children were older (2.3 ± 2.2 years vs. 1.0 ± 1.0 years), more likely to be diagnosed with bronchopneumonia (57.5% vs. 31.6%), but also had a lower hospitalization rate, shorter hospital stay, less oxygen use, and less respiratory distress than those in 2016-2019 (all p value < 0.05). The RSV isolates in 2020 belonged to RSV-A subtype ON1 but were phylogenetically distinct from the ON1 strains prevalent in Taiwan previously., Conclusion: The 2020 RSV outbreak was led by the novel RSV-A subtype ON1 variant with clinical manifestations distinct from previous years. Continuous surveillance of new emerging variants of respiratory viruses in the post-pandemic era is warranted., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

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 < 0.05)., Conclusion: Early diagnosis and determination of MRMP are needed for effective management of MP infection., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

From January 2019 to May 2021, 11 children underwent allogeneic stem cell transplantation at our institute. Four of them received letermovir for cytomegalovirus prophylaxis. Three children, none of whom received prophylaxis, experienced cytomegalovirus reactivation. Letermovir is a promising medication for use in cytomegalovirus prophylaxis in children. Further studies are warranted., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Group A Streptococcus (GAS) is an important pathogen causing morbidity and mortality worldwide. Surveillance of resistance and emm type has important implication to provide helpful information on the changing GAS epidemiology and empirical treatment., Methods: To study the emergence of resistant GAS in children with upper respiratory tract infection (URTI), a retrospective study was conducted from 2000 to 2019 in southern Taiwan. Microbiological studies, including antibiotic susceptibility, were performed. GAS emm types and sequences were determined by molecular methods. The population was divided into two separate decades to analyze potential changes over time. The 1st decade was 2000-2009; the 2nd decade was 2010-2019. Multivariate analyses were performed to identify independent risk factors associated with macrolide resistance between these periods., Results: A total of 320 GAS from 339 children were enrolled. Most of the children (75%) were under 9 years of age. The most common diagnosis was scarlet fever (225, 66.4%), and the frequency increased from 54.8% in the 1st to 77.9% in the 2nd decade (p < 0.0001). There was a significant increase in resistance to erythromycin and azithromycin from 18.1%, 19.3% in the 1st to 58.4%, 61.0% in the 2nd decade (p < 0.0001). This was associated with clonal expansion of the GAS emm12-ST36 which carrying erm(B) and tet(M) from 3.0% in the 1st to 53.2% in the 2nd decade (p < 0.0001)., Conclusions: Significant emergence of macrolide-resistant GAS emm12-ST36 in children supports the need for continuing surveillance and investigation for the clonal virulence., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

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

Background: Human adenoviruses (HAdV) are important pathogens of pediatric respiratory tract infections in Taiwan. There were two major HAdV epidemics in southern Taiwan in 2011 and 2014, respectively., Methods: The demographic, clinical characteristics, and risk factors for hospitalization of pediatric patients with HAdV infection in the two outbreaks were retrospectively compared. The epidemic was defined as > 7% HAdV detection rate for six consecutive weeks. HAdV infection was defined as positive HAdV isolates from respiratory tract specimens. HAdV genotype was determined by PCR-based hexon gene sequencing., Results: A total of 1145 pediatric patients were identified (635 cases in 2011; 510 cases in 2014). HAdV genotype 3 and 7 contributed to both epidemics, although the proportion of HAdV3 decreased significantly (64.7% in 2011 to 25.5% in 2014, p < 0.001) and was replaced by other genotypes (type 1, 4, and 6) in the 2014 epidemic. Among the hospitalized patients, there were more patients hospitalized with bronchopneumonia/or pneumonia in the 2011 epidemic (10.6% vs 5.1%, p < 0.001), while more patients hospitalized with acute pharyngitis/pharyngoconjunctival fever (63.9% vs. 38.6%, p < 0.001) in the 2014 epidemic. In both epidemics, hospitalized patients had higher WBC and C-reactive protein (CRP) levels than non-hospitalized patients. Using multivariate regression analysis, underlying disease and elevated CRP levels were independent risk factors for hospitalization in both epidemics., Conclusion: There were significant differences in clinical, viral characteristics and risk factors of hospitalization between the 2011 and 2014 epidemics. Understanding changes in the epidemiological and clinical characteristics of HAdV epidemics is important from a public health perspective.

Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia., (Copyright © 2019. Published by Elsevier B.V.)

Background: Human parainfluenza viruses (HPIV) 1-4 had been analyzed as being one of the most frequent causes of hospitalizations for young children with respiratory tract illnesses., Methods: This retrospective study was performed from children virologically confirmed as HPIV infection through throat swab or nasopharyngeal aspirates at a tertiary care university hospital, between January 2012 and December 2014. HPIV4 was not checked and analyzed, due to not include in the commercial kit. The demographic, epidemiological, clinical presentations, diagnosis, treatment, outcomes, and laboratory data were analyzed., Results: Totally 398 cases were enrolled, including 39 (9.8%) of HPIV1, 67 (16.8%) of HPIV2, and 292 (73.4%) of HPIV3. The mean age of HPIV-infected children was 2.9 year-old, and 50.5% were among one to three year-old. A total of 56.8% HPIV3-infected children were among one to three years old, however, no HPIV2-infected children was younger than one year-old. The HPIV1-infected patients were more common to develop wheezing and diagnose as acute bronchiolitis. HPIV2-infected children were more likely to have hoarseness (23.9%), and were associated with croup (25.4%). HPIV3 was isolated from two fatal cases, with neurological underlying diseases., Conclusion: The impact caused by HPIVs infections is significant in hospitalized children. In the current study, our results contribute to the epidemiologic, clinical and laboratory information of HPIV infection in children in the important areas of respiratory tract infection that could support the development of optimization management., (Copyright © 2017. Published by Elsevier B.V.)

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 2014-2016, followed by norovirus and rotavirus. Further monitoring of epidemiology characteristics among cardinal pathogens of pediatric gastroenteritis is necessary., (Copyright © 2017. Published by Elsevier B.V.)

Background: Group A streptococcus (GAS) is a common pathogen in children. Macrolide resistance in GAS has been described worldwide. The aims of this study are to analyze macrolide resistance of GAS isolates in southern Taiwan and to clarify the relationship of emm typing and macrolide resistance in the past decade., Methods: All GAS isolated from patients younger than 18 years at a single tertiary center in southern Taiwan were collected from 2000 to 2012. Antibiotics susceptibility to erythromycin, azithromycin, and clindamycin were determined by agar dilution method, and were interpreted by Clinical and Laboratory Standards Institute (CLSI) standards. emm typing was performed by polymerase chain reaction (PCR)., Results: A total of 301 isolates were collected during the period of 13 years. Scarlet fever (38.5%) and acute pharyngitis (32.2%) were the most common diagnosis. Decreased resistance rate of erythromycin from 53.1% in 2000 to 0% in 2010 was found, but it increased rapidly to 65% in 2011. The resistance rate of azithromycin was the lowest (4.2%) in 2005, but was higher than 15% after 2006. The involvement of the erythromycin resistance genes were mefA (53.1%), ermB (35.9%), and ermTR (10.9%). The resistance of clindamycin also increased since 2011. emm12 was the most common serotype and accounted for 44.9% of all isolates. Compared with the non-emm12 group, resistance to erythromycin, azithromycin, and clindamycin were more frequently detected in the emm12 group., Conclusion: Increased resistance of GAS to macrolide and clindamycin was found in recent years. emm12 was the main serotype for macrolide resistance., (Copyright © 2013. Published by Elsevier B.V.)

Background/purpose: Childhood tuberculosis (TB) continues to be a major public health problem in Taiwan. Taiwan remains a highly endemic area despite neonatal Bacillus Calmette-Guérin (BCG) vaccination and the availability of anti-TB therapy. The presentation is highly variable and it is often difficult to make an accurate diagnosis. This study was designed to evaluate the demographic, clinical, and laboratory findings and outcomes of TB in children with emphasis on central nervous system (CNS) complications., Methods: The medical records of 80 children diagnosed with TB at a medical center in southern Taiwan over the past 24 years (1988-2012) were reviewed., Results: Among them, 48.8% (39/80) had pulmonary TB, 27.5% (22/80) had isolated extrapulmonary TB, and 23.7% (19/80) had disseminated TB. Most infected cases were aged either < 4 years or > 12 years. TB contact history was found in 42.5% (34/80) cases. Fourteen (17.5%) of the cases had CNS involvement. The most common presentations were fever (85.7%), signs of increased intracranial pressure (71.4%), drowsiness (64.3%), and focal neurological signs (57.1%). The major radiological findings were tuberculoma (50%), basilar enhancement (41.6%), infarction (41.6%), hydrocephalus (16.6%), and transverse myelitis (16.6%). The case fatality of CNS TB was 14.3% and 21.4% had neurologic sequelae., Conclusion: Findings suggest that positive exposure history and suspicious clinical presentations are important clues for further confirmatory laboratory and image studies in childhood TB. CNS TB usually presented as part of disseminated TB in children. Early diagnosis and treatment may lead to favorable outcomes in CNS TB., (Copyright © 2013. Published by Elsevier B.V.)

Background: Recently, the proportion of adolescents diagnosed with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) has increased. The aim of this study is to evaluate the clinical and laboratory characteristics of HIV-infected adolescents in southern Taiwan., Methods: From June 1997 to December 2010, a total of 40 HIV-infected adolescents who sought medical care in a university hospital in southern Taiwan were enrolled in the study. They were classified into three HIV at-risk groups, men who have sex with men (MSM), heterosexuals, and intravenous drug users (IDUs). Clinical and laboratory data were obtained from medical records., Results: The median age of the 40 HIV-infected adolescents was 19 years. The HIV at-risk groups were MSM (22/40, 55%), heterosexuals (7/40, 17.5%), IDUs (5/40, 12.5%), and unknown (6/40, 15%). The initial median CD4 count and log plasma HIV viral load were 318 cells/mm(3) and 4.61, respectively. The seroprevalence of anti-HAV, anti-HBc, anti-HCV antibodies and HBsAg was 5.3%, 26.1%, 13% and 13%, respectively. Among 17 adolescents who had regular follow-ups more than twice, 7 (41.2%) had a concurrent sexually transmitted disease (STD). The most common STD was genital warts (41.2%) followed by syphilis (11.8%). Among 7 patients who received highly active antiretroviral agents (HAART) for more than 12 months, 5 (71.4%) had sustained virologic suppression., Conclusion: MSM are the largest risk group in HIV-infected adolescents in southern Taiwan and are characterized by a high prevalence of anogenital warts and low seroprevalence of anti-HAV., (Copyright © 2012. Published by Elsevier B.V.)

Aim: Streptococcus pneumoniae-associated haemolytic uraemic syndrome (SP-HUS) is a major concern of paediatric acute renal failure in Taiwan; it leads to significant morbidity and mortality during the acute phase and to long-term morbidity after an acute episode., Methods: Twenty children diagnosed with HUS between 1 May 1995, and 31 December 2008 was enrolled. Clinical variables related to laboratory data, organ involved, and outcomes were examined between patients with and without SP-HUS., Results: Thirteen of the 20 (13/20, 65%) patients required dialysis, nine (9/20, 45.0%) developed hepatic dysfunction, disseminated intravascular coagulation (DIC), gastrointestinal bleeding, and hypertension, respectively. They were the second most common extrarenal complication except empyema (11/20, 55%). Two (10%) died and seven (35%) of the survivors developed long-term renal morbidity. Twelve of the 20 patients (60%) were diagnosed with SP-HUS. Younger age, female children, higher white blood cell count, higher alanine transaminase, higher lactate dehydrogenase and high incidence of DIC were significantly common in SP-HUS cases. All SP-HUS cases were complicated with pleural effusion, empyema, or both. Positive Thomsen-Freidenreich antigen (T-Ag) activation was 83% sensitive and 100% specific for SP-HUS, and a positive direct Coombs' test was 58% sensitive and 100% specific., Conclusion: Invasive pneumococcal infection is the most common cause of HUS in Taiwan. Positive T-Ag activation and a direct Coombs' test are rapid predictors of SP-HUS in children with invasive pneumonia., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Tuberculosis (TB) is an important public health issue in Taiwan and worldwide. Taiwan has made major progress in combating TB in the past 40 years. However, childhood TB still constitutes a significant challenge in disease control. From January to mid December 2011, 369 new cases of pediatric TB were confirmed. The relatively low case number and variable clinical presentations made it difficult for early detection. Latent TB infections in children also pose further complexity in clinical management. Knowledge of the clinical features of active and latent TB infection is crucial for efficient TB control., (Copyright © 2011. Published by Elsevier B.V.)

Eighty cases of echovirus 18 infection among young children during an outbreak in 2006 in Taiwan were enrolled. Twenty percent of the patients had a comorbid condition. Twenty-five cases (31%) were complicated by aseptic meningitis. The most frequent diagnoses in children without meningitis were pharyngitis/tonsillitis (35%) and vesicular viral exanthem (33%). The case-fatality rate among the children with meningitis was 4%. Echovirus 18 was isolated from the cerebrospinal fluid of 68% of the children.

Background/purpose: Healthcare-associated infections in neonatal intensive care units (NICUs) are associated with a significant risk of morbidity and mortality. Knowledge regarding pathogens, primary sources of infection and antibiotic resistance in the NICU is essential for developing management strategies. This study aimed to analyze the long-term characteristics of healthcare-associated infections in a tertiary referral center in southern Taiwan., Methods: Infants < 30 days old, with positive blood, cerebrospinal fluid, urine or tissue fluid cultures during hospitalization in the NICU of National Cheng Kung University Hospital from July 1989 to June 2008 were included in the study., Results: In total, 1,417 organisms and episodes were identified during the study period. Gram-positive organisms, Gram-negative organisms and fungi constituted 923 (65.1%), 358 (25.3%) and 136 (9.6%) of the pathogens, respectively. Of the Gram-positive organisms, coagulase-negative staphylococci (51.5%), Staphylococcus aureus (34.8%) and Enterococcus spp. (6.1%) were the major pathogens; and 27% of Staphylococcus aureus isolates were oxacillin-resistant. For the Gram-negative organisms, Klebsiella pneumoniae (22%), Pseudomonas aeruginosa (21.8%), Escherichia coli (16.7%) and Enterobacter cloacae (16.7%) were dominant. Also, Candida albicans accounted for 50% of fungal infections. The most common source of infection was bloodstream infection (59.0%), and 5.6% of these were catheter-related. Skin and soft tissue infections were also frequent (26.3%)., Conclusion: Bloodstream and skin/soft tissue infections caused by commensal species play an important role in healthcare-associated infections in the NICU. New measures should be developed in response to the changing patterns in the NICU., (Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.)

Enterovirus 71 (EV71) has emerged as a significant cause of brainstem encephalitis and acute flaccid paralysis in Taiwan. It may be complicated by autonomic nervous system dysregulation and pulmonary edema (PE). Cytokines in the central nervous system and systemic inflammatory responses play important roles in the pathogenesis of EV71-associated PE. Pathogenesis-based management with intravenous immunoglobulin and milrinone has been associated with reduced mortality in children with severe EV71 infections.

Background and Purpose: An outbreak of influenza A and influenza B appeared at the beginning and end of 2006 in southern Taiwan. We conducted this study to test whether laboratory findings could differentiate influenza A from influenza B infection., Methods: All children aged 16 years or less, who had nasal and/or throat swabs sent from inpatient or outpatient settings at National Cheng Kung University Hospital for the diagnosis of influenza infection from January 2005 to February 2007, were considered eligible subjects. Retrospective chart review of clinical and laboratory data was performed., Results: 274 patients were enrolled, 151 with influenza A and 123 with influenza B, of whom 127 (46.4%) received laboratory examinations. The peak month of influenza A and influenza B infections was January 2006 and January 2007, respectively. Children with influenza B infections were older than those with influenza A infections (p<0.001). Influenza B-infected patients were more likely to have myalgia (p=0.004) than those with influenza A infections. Furthermore, children with influenza B infections tended to have lower leukocyte counts (6383 +/- 3970/mm3 vs 7639 +/- 3476/mm3, p=0.004), and higher serum creatine kinase level (p=0.002) than those with influenza A infections. The clinical outcomes were usually favorable., Conclusions: The clinical features of influenza B and influenza A infections are similar. However, decreased leukocytes and increased serum creatine kinase can be used as adjunctive criteria for diagnosis of influenza B infection before viral culture results are available.

Amis is the largest aboriginal population in Taiwan. The previous dermatoglyphic studies of the Amis only reported limited data. In this study, we collected and analyzed the dermatoglyphs of 200 Amis individuals, and we reported a wide range of dermatoglyphic variables including total finger ridge count, a-b ridge count, atd angle, axial triradius percent distance, and frequencies of fingerprint pattern, palmar thenar pattern, palmar interdigital pattern, and simian line. This study is the first comprehensive dermatoglyphic research of Amis since 1960s, and its dermatoglyphic data will be useful for future research in anthropology, genetics and medicine.