Assessing the utilization of antimicrobial agents in pediatric pneumonia during the era of the 13-valent pneumococcal conjugate vaccine: A retrospective, single-center study.

BACKGROUND AND PURPOSE: Pneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. METHODS: This retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. RESULTS: The cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = -0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = -0.006, p = 0.787 and rs = -0.156, p = 0.398). CONCLUSION: After the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia and pneumonia.

Building nomogram plots for predicting urinary tract infections in children less than three years of age.

BACKGROUND AND PURPOSE: Urinary tract infections (UTIs) are the most common bacterial infection in young children. This study aimed to formulate nomogram plots for clinicians to predict UTIs in children aged <3 years by evaluating the risk factors for UTIs in these children. METHODS: This retrospective study was conducted at a tertiary medical center from December 2017 to November 2020. Children less than three years of age were eligible for the study if they had undergone both urine culture and urinalysis during the study period. Mixed-effects logistic regression models with a stepwise procedure were used to determine the relationship between outcome (positive/negative UTI) and covariates of interest (e.g., weight percentile, laboratory) for each patient. Nomogram plots were constructed on the basis of significant factors. We repeated the analysis thrice to adapt it to three different medical settings: medical centers, regional hospitals, and local clinics. RESULTS: In the medical center setting, the two most significant factors were urine leukocyte count ≥100 (OR =8.87; 95% CI (Confidence Interval), 4.135-19.027) and urine nitrite level (OR =8.809; 95% CI, 5.009-15.489). The two factors showed similar significance at the regional hospital and local clinic settings. Abnormal renal echo findings were positively correlated with UTI in the medical center setting (OR =2.534; 95% CI 1.757-3.655). Three nomogram plots for the prediction of UTIs were drawn for medical centers, regional hospitals, and local clinics. CONCLUSION: Using the three nomogram plots, frontline doctors can formulate the probabilities of pediatric UTIs for better decision-making.

Antimicrobial susceptibility and serotype replacement of Streptococcus pneumoniae in children before and after PCV13 introduction in Taiwan.

BACKGROUND: Since 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections. METHODS: Children with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration. RESULTS: In total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p < 0.001). The prevalence of serotype 19 A had increased gradually since 2010 but declined rapidly after 2013. Serotypes 15 A and 23 A were the most common serotypes after 2015. The non-susceptibility of the S. pneumoniae isolates to penicillin, cefotaxime, and ceftriaxone decreased. Based on meningitis breakpoints, the non-susceptibility to cefotaxime and ceftriaxone gradually decreased, but increased in 2020. CONCLUSION: PCV13 was considerably effective in reducing the incidence of IPD in children; however, the prevalence of serotypes 15 A and 23 A increased. The increase in antimicrobial non-susceptibility caused by non-vaccine serotypes must be continuously monitored.

Jaundice-predominant manifestation of Kawasaki disease in children.

Background: A jaundice-predominant presentation of Kawasaki disease (KD) is atypical. Methods: A total of 12 children with KD with a predominant manifestation of jaundice at MacKay Children's Hospital were reviewed, along with 42 cases reported in the literature since 1990. Results: The median age of the 12 patients was 1.85 years (range: 3 months-4 years), and 66.6% were male. All of the patients had elevated liver function at presentation, 50% had hydrops of the gallbladder, and almost 60% had gastrointestinal symptoms and signs. Complete KD was evident in 11 of the 12 patients (91.7%), and two patients (16.7%) had recurrent episodes. All of the patients received intravenous immunoglobulin (IVIG); however, one-third were refractory to treatment. Corticosteroids were used in five (41.7%) of the patients. Three (25%) of the patients had shock, and seven (58.3%) had coronary artery abnormalities, of whom one (8.3%) had persistent coronary artery aneurysm and the others recovered. A review of the 42 cases in the literature showed that the children with a jaundice-predominant presentation of KD had high rates of IVIG-refractory disease (25%), coronary artery abnormalities (25%), shock (13.2%), and corticosteroid treatment (24.2%). Conclusions: Children with KD presenting with a jaundice-predominant manifestation are at a higher risk of IVIG-refractory disease, coronary artery abnormalities, and more recurrent episodes. Physicians should be aware of the risk of shock in this population.

The experience of using FilmArray Meningitis/Encephalitis Panel for the diagnosis of meningitis and encephalitis in pediatric patients.

BACKGROUND/PURPOSE: Central nervous system infections can cause severe complications and even death in children. Early diagnosis of the causative pathogen can guide appropriate treatment and improve outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) is a multiplex polymerase chain reaction (PCR) assay targeting 14 pathogens. We aimed to examine FA-ME performance compared with conventional assays and its effect on antimicrobial usage. METHODS: We prospectively enrolled 55 pediatric patients with suspected meningitis or encephalitis and simultaneously performed FA-ME and conventional assays. Sixty-three hospitalized patients with CNS infection before implementing FA-ME were considered controls. We compared the FA-ME results with conventional assays and the empiric antimicrobial usage and hospital stay between the two study groups. RESULTS: Nine patients (16.4%) tested positive by FA-ME, four were bacterial, and five were viral. Three additional pathogens were detected by conventional assays: Enterococcus faecalis, Leptospira, and herpes simplex virus type 2. In the control group, two bacterial pathogens were detected by CSF culture and four viral pathogens by single PCRs. Compared with the control group, the FA-ME group had a shorter time for pathogen detection, but there were no significant differences in pathogen detection rate, duration of empiric antimicrobial therapy, and length of hospital stay. CONCLUSION: Although no significant difference was found in empiric antimicrobial duration and length of stay between patients tested with FA-ME and conventional assays, FA-ME had the advantage of a shorter detection time and early exclusion of potential causative pathogens. The FA-ME results should be interpreted carefully based on the clinical presentation.

A randomized trial of vitamin D supplementation to prevent seasonal influenza and enterovirus infection in children.

PURPOSE: This study aimed to evaluate whether vitamin D supplementation can reduce the incidence of influenza and enterovirus infection in Taiwanese children. METHODS: This randomized, double-blind, controlled trial included children aged two to five years between April 2018 and October 2019 from daycare centers. All the participants were randomly assigned to a vitamin D supplementation group (2000 IU/day) or placebo group for one month. The primary outcome was the incidence of influenza and enterovirus infection in the following six months, and the secondary outcome was the incidence of influenza and enterovirus infection in the children's household members. RESULTS: Two hundred and forty-eight children participated. The vitamin D group showed a relative risk reduction of 84% against influenza compared to the placebo group but did not reach statistical significance. Kaplan-Meier curves revealed that the placebo group had a higher probability of influenza infection than the vitamin D group (log-rank test, p = 0.055), but the incidence of enterovirus infection was similar between the two groups (p = 0.946) among children. Among children's household members, the incidence of influenza (p = 0.586) and enterovirus infection (p = 0.528) were both similar between the two groups. All children who were tested for serum 25(OH)D levels after vitamin D intervention had 25(OH)D levels above 30 ng/ml CONCLUSION: Vitamin D supplementation may have a small preventative effect against influenza infection but does not affect enterovirus infection among preschool children. A high-dose short-term vitamin D intervention might be a way to elevate children's serum vitamin D levels in the first month of starting kindergarten.

Reducing catheter related bloodstream infection risk of infant with a prophylactic antibiotic therapy before removing peripherally inserted central catheter: A retrospective study.

PURPOSE: This study examined the efficacy of prescribing antibiotics, specifically a single dose of vancomycin, in reducing the incidence of culture-positive and culture-negative sepsis prior to the removal of peripherally inserted central catheters (PICCs). MATERIALS AND METHODS: We retrospectively reviewed charts of infants who had PICCs in a tertiary level hospital during the period from 2010 to 2019. The incidence of post-catheter removal clinical sepsis between the groups with or without antibiotics was compared. The antibiotic group was defined by receiving a single dose of vancomycin or any other antibiotic prior to line removal. RESULTS: We enrolled 585 PICC removal episodes in 546 infants for analysis. Antibiotics were given prior to removal in 257 cases (43.9%) and not given prior to removal in 328 cases (56.1%). There were 13 episodes of post-catheter removal clinical sepsis detected within 72 h (2.2%), 2 of which were culture-positive (0.3%). A 9.3-fold decrease in the odds for clinical sepsis was observed in the antibiotic group (p = 0.01). The incidence of post-catheter removal sepsis was decreased by a single prophylactic dose of vancomycin (p = 0.02), whereas the use of other antibiotics showed no effect (p = 0.35). Logistic regression analysis demonstrated that comorbidities with gastrointestinal diseases (p = 0.01), PICC insertion sites in the scalp and neck (p = 0.04), and no vancomycin administration prior to line removal (p = 0.02) were independent risk factors for subsequent clinical sepsis. CONCLUSION: A single prophylactic dose of vancomycin prior to PICC line removal might reduce clinical sepsis events in infants.

To mix or not to mix? A rapid systematic review of heterologous prime-boost covid-19 vaccination.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has had an enormous impact worldwide, and vaccination is believed to be the method that will control the pandemic. Several types of vaccines developed using different platforms have been authorized, but the immunogenicity and reactogenicity of heterologous prime-boost vaccination with different vaccines remain largely unclear. AREAS COVERED: Electronic databases including PubMed, Embase, medRxiv, Research Square, and SSRN were searched to investigate the immunogenicity and reactogenicity associated with heterologous vaccination.As of 30 June 2021, four trials including 1,862 participants were identified. Heterologous administration of BNT162b2 (BNT) in ChAdOx1 (ChAd)-primed participants (ChAd/BNT) showed noninferior immunogenicity to homologous BNT administration (both prime and booster were BNT vaccines, BNT/BNT) with tolerable reactogenicity and higher T cell responses. Compared with homologous ChAdOX1 vaccination (ChAd/ChAd), heterologous ChAd/BNT was found to elicit higher immunogenicity (ChAd/BNT vs. ChAd/ChAd, antibody titer ratio: 9.2). EXPERT OPINION: Our systematic review found robust immunogenicity and tolerable reactogenicity of heterologous administration of a BNT162b2 boost in ChAdOx1-primed participants. An additional benefit of stronger T cellular immunity was also observed. Heterologous vaccination is a reasonable and feasible strategy to combat COVID-19. Further studies are warranted to confirm the benefits and identify the optimal combinations, doses, and intervals.

Efficacy of clarithromycin-naproxen-oseltamivir combination therapy versus oseltamivir alone in hospitalized pediatric influenza patients.

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.

Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample.

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10-5; C allele, OR = 1.32, P = 8.1 × 10-4). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.

Clinical features of neonatal listeriosis in Taiwan: A hospital-based study.

BACKGROUND: Neonatal listeriosis is a major cause of mortality in newborn; however, there is limited information about this disease in Taiwan. The aim of our study was to identify the outcome determinants, clinical features, and incidence of pregnancy-associated listeriosis, which includes both neonatal and maternal listeriosis. METHODS: We retrospectively analyzed the medical records of neonatal and maternal patients with pregnancy-associated listeriosis at two hospitals in Taiwan from January 2000 to December 2018. Listeriosis was indicated by positive Listeria monocytogenes culture. RESULTS: Our study examined 18 neonates and 19 mothers. The neonatal and fetal death rate was 24%. All five cases of fetal losses or neonatal deaths occurred before 29 weeks of gestational age. The annual incidence of confirmed neonatal listeriosis increased significantly from 0.94/10,000 neonatal inpatients in 2000-2011 to 5.45/10,000 neonatal inpatients in 2012-2018 (p = 0.026). Clinical presentations of neonatal listeriosis included respiratory distress (85%), leukocytosis or leukopenia (77%), bandemia (69%), thrombocytopenia (77%), hypocalcemia (100%) and elevated C-reactive protein (CRP) levels (92%). Lower gestation correlated with a higher fatality rate (p = 0.002). Among the maternal cases investigated, 67% had a diagnosis of listeriosis, and 72% presented with fever. However, only 21% of the 19 mothers received complete antepartum ampicillin treatment. CONCLUSIONS: The incidence of neonatal listeriosis is increasing, especially in preterm neonates. Maternal listeriosis should be adequately treated with appropriate empirical antibiotics.

Respiratory tract infections in children with tracheostomy.

BACKGROUND: Children with tracheostomy are at increased risk for respiratory tract infections, yet the risk involved in tracheostomy related infections is unclear. METHODS: We conducted a retrospective review of the medical records of children who underwent tracheostomy between January 2002 and December 2016 at a teaching hospital in Taipei. Demographics, underlying disease, indication for tracheostomy, laboratory data and management, and long-term outcome data were collected. Infection episodes were grouped into definite, possible, non-bacterial pneumonia, and local infection groups. RESULTS: Ninety patients were enrolled. Forty-two (46.7%) patients had infections that required hospitalization. Definite bacterial pneumonia accounted for 12 (8.5%) episodes, 113 episodes (80.1%) were possible bacterial pneumonia, 12 (8.5%) were non-bacterial pneumonia, and 4 (2.8%) were local infections. Patients with definite and possible bacterial pneumonia were found to have a longer hospital duration than patients with non-bacterial pneumonia (p=0.024), with mean hospitalization stays of 8.83±5.59 days and 5.67±2.55 days, respectively. The median duration from tracheostomy to bacterial pneumonia was 1.78 years (range, 0.04- 11.38) whereas for the non-bacterial pneumonia group it was 0.57 years (range, 0.04-6.61). Cerebral palsy (CP) (adjusted odds ratio [AOR] 3.65; 95% confidence interval [CI]: 1.11-11.99; p=0.033) and gastroesophageal reflux disease (GERD) (AOR 2.84; 95% CI: 1.09-7.38; p=0.033) were independently associated with respiratory tract infections in these children. CONCLUSION: In this study, CP and GERD were associated with infections in children with tracheostomy. Bacterial and non-bacterial pneumonia are difficult to differentiate clinically which may lead to unnecessary antibiotics use.

Effects of influenza vaccine and sun exposure time against laboratory-confirmed influenza hospitalizations among young children during the 2012-13 to 2015-16 influenza seasons.

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 < 0.01; odds ratio (OR), 0.427; 95% confidence interval (CI), 0.306-0.594]. Children with mean sun exposure time of >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 < 0.05; OR, 0.667; 95% CI, 0.491-0.906). CONCLUSIONS: Seasonal influenza vaccination effectively prevents influenza-related hospitalizations in children aged ≤5 years. Besides, >7 h of sun exposure/week may also be associated with lower risk of influenza-related hospitalizations in children.

Childhood otitis media: Relationship with daycare attendance, harsh parenting, and maternal mental health.

Psychological stress has been linked to developmental problems and poor health in children, but it is unclear whether it is also related to otitis media (OM). As part of a long-term study surveying the characteristics of childcare and development in Taiwan, we analyzed the relationship between OM and sources of psychological stress in children, such as poor maternal mental health and harsh parental discipline. We analyzed the data of 1998 children from the "Kids in Taiwan: National Longitudinal Study of Child Development & Care (KIT) Project" at the age of 3 years. Using bivariate and multivariate logistic regression models, we tested several risk factors as potential independent predictors of two outcomes: parent-reported incidence of OM and child health. The proportion of children who had developed OM in the first 3 years of their life was 12.5%. Daycare attendance (odds ratio [OR]: 1.475; 95% confidence interval [CI]: 1.063-2.046), poor maternal mental health (OR: 1.913; 95% CI: 1.315-2.784), and harsh parental discipline (OR: 1.091; 95% CI: 1.025-1.161) correlated with parent-reported occurrence of OM. These findings suggest that providing psychosocial support to both parents and children might be a novel strategy for preventing OM.

The epidemiology of non-typhoidal Salmonella gastroenteritis and Campylobacter gastroenteritis in pediatric inpatients in northern Taiwan.

BACKGROUND: Campylobacter and Non-typhoidal Salmonella (NTS) are the two most common bacterial pathogens associated with acute gastroenteritis in children. This study aims to elucidate the epidemiology of Campylobacter and NTS gastroenteritis and develop a scoring system to differentiate them. MATERIALS AND METHODS: This retrospective study enrolled 886 children ≤18 years of age, hospitalized due to acute gastroenteritis with stool culture-proven Campylobacter or NTS infection from July 2012 to December 2015. Pearson's chi-square test and multivariate logistic regression were used to compare clinical manifestations and laboratory data. Receiver operating characteristic curves were plotted to evaluate the scoring system. RESULTS: Seasonality was found in NTS gastroenteritis from May to September, but no seasonality in Campylobacter gastroenteritis. Campylobacter jejuni and Salmonella serogroup B were the most common pathogens. The median ages were 68.2 and 18.5 months and the incidence rates of bacteremia were 0.6% and 7.1% in the Campylobacter and NTS groups, respectively. Salmonella serogroup C2 infection had the highest risk of bacteremia (OR: 5.9, 95% CI: 2.8-12.7, p < 0.001). Multivariate analysis showed significant differences in sex, age, fever, dehydration, immature WBC, CRP and Na between the two groups. A score of ≥2 points indicated Campylobacter gastroenteritis, with sensitivity 75%, specificity 77%. The positive and negative predictive values were of 73.3% and 93.9% after validation. CONCLUSION: Campylobacter gastroenteritis is associated with older age and male sex, while NTS gastroenteritis is associated with moderate to severe dehydration and bacteremia. Salmonella serogroup C2 infection has the highest risk of bacteremia.

Epidemiology and antimicrobial susceptibility of non-typeable Haemophilus influenzae in otitis media in Taiwanese children.

BACKGROUND: Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM. METHODS: Middle ear fluid samples from children <18 years with OM were obtained from 2010 to 2015. For culture-positive episodes (Streptococcus pneumoniae, H. influenzae, Moraxella catarrhalis, and Streptococcus pyogenes), patients' demographic and clinical information were reviewed and analyzed. RESULTS: A total of 783 episodes were included with 31.8% of isolates as positive. S. pneumoniae was recovered in 69.4%, NTHi in 24.6%, M. catarrhalis in 5.6%, and S. pyogenes in 4.0% of culture-positive episodes. The proportion of pneumococcal OM has declined since 2012 (P for trend <0.005), but NTHi OM rose simultaneously (P for trend = 0.009). Factors associated with increased risk of NTHi infection included less spontaneous otorrhea (OR 0.15, 95% CI 0.06-0.39, P < 0.001), absence of fever (OR 0.30, 95% CI 0.14-0.66, P = 0.003), concurrent sinusitis (OR 2.91, 95% CI 1.36-6.20, P = 0.006), previous ventilation tube insertion (OR 12.02, 95% CI 3.15-45.92, P < 0.001) and recurrent OM (OR 3.43, 95% CI 1.01-11.71, P = 0.049). The susceptibility of NTHi to amoxicillin/clavulanate was 82.0%. CONCLUSIONS: NTHi OM has trended upward in the post-PCV era. Concurrent sinusitis, previous ventilation tube insertion, and recurrent OM were associated with NTHi OM implicated a correlation between NTHi and complex OM. In consideration of NTHi infection, we suggest amoxicillin/clavulanate as the first-line therapy for OM among Taiwanese children.

Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells.

Influenza A (H7N9) is an emerging zoonotic pathogen with pandemic potential. To understand its adaptation capability, we examined the genetic changes and cellular responses following serial infections of A (H7N9) in primary human airway epithelial cells (hAECs). After 35 serial passages, six amino acid mutations were found, i.e. HA (R54G, T160A, Q226L, H3 numbering), NA (K289R, or K292R for N2 numbering), NP (V363V/I) and PB2 (L/R332R). The mutations in HA enabled A(H7N9) virus to bind with higher affinity (from 39.2% to 53.4%) to sialic acid α2,6-galactose (SAα2,6-Gal) linked receptors. A greater production of proinflammatory cytokines in hAECs was elicited at later passages together with earlier peaking at 24 hours post infection of IL-6, MIP-1α, and MCP-1 levels. Viral replication capacity in hAECs maintained at similar levels throughout the 35 passages. In conclusion, during the serial infections of hAECs by influenza A(H7N9) virus, enhanced binding of virion to cell receptors with subsequent stronger innate cell response were noted, but no enhancement of viral replication could be observed. This indicates the existence of possible evolutional hurdle for influenza A(H7N9) virus to transmit efficiently from human to human.

A National Seroepidemiologic Survey of Pertussis Among School Children in Taiwan.

BACKGROUND: In 2009, a booster dose of acellular pertussis vaccine for children at or before entry to elementary school was added to the national immunization program in Taiwan, which includes pertussis vaccination at 2, 4, 6 and 18 months of age. In 2013, a study to assess the level of humoral immunity against pertussis in elementary and junior high school children and adolescents was conducted. METHODS: A multistage stratified systematic sampling method was applied to randomly selected grade 1 to 9 school children for testing. Serum samples were tested for IgG antibodies to Bordetella pertussis using commercial enzyme-linked immunosorbent assay kits. The study collected information on sociodemographic characteristics, vaccination history, sibling number and disease history of pertussis. RESULTS: The study recruited 2782 school children from 58 schools around the country. By questionnaire, only 1% (28/2782) students had history of pertussis. The overall positivity rate of anti-B. pertussis IgG was 42.5%, and the rates were not different between the 5 geographical areas (range from 39.6% to 44.6%, P = 0.375). Age-stratified data showed that the positivity rates were 43.6-48.8% among grade 1-3 students, 26.6-28.7% in grade 4-5 students and increased progressively from 39.4% to 51.3% in grade 6-9 students. The overall positivity rate was significantly higher in the nonbooster group (46.4% versus 38.6%, P < 0.01). CONCLUSION: The prevalence of anti-B. pertussis antibody was 42.5% in grade 1-9 students under the current vaccination program in Taiwan. Antibody induced by the booster vaccination before entry of primary school waned rapidly in 3-4 years. Rapid waning of anti-B. pertussis antibody may explain the resurgence of whooping cough in recent decades. Additional booster doses should be considered in adolescents and adults.

Redistribution of Streptococcus pneumoniae Serotypes After Nationwide 13-valent Pneumococcal Conjugate Vaccine Program in Children in Northern Taiwan.

BACKGROUND: After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy. METHODS: S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities. RESULTS: Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P < 0.0001) but nonvaccine serotypes increased from 8.8% to 51.5% (P < 0.0001). CONCLUSIONS: The step-by-step PCV13 national immunization program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.