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Appropriate mitigation strategy to minimize enterovirus (EV) transmission among children is essential to control severe EV epidemics. Scientific evidence for the effectiveness of case isolation and class suspension is lacking.EV-infected children ≤ eight years are asked to stay at home for seven days. Classes were suspended for seven days if there are more than two classmates having an onset of herpangina or hand, foot, and mouth disease in one classroom within one week. Study subjects are divided into two groups, group A with class suspension for one week and group B without class suspension.Among 4153 reported EV-infected children from 1085 classes in May and June, 2015 were enrolled. Median incidence of EV infection in a class was 7% (range 3% -60%). The incidence was higher in group A (median 14%, range 3-60%) than that in group B (median 6%, range 3-80%) (P 0.01). The median incidence is highest in day care center (20%), followed by kindergarten (8%), and primary school (4%) (P 0.01). Most secondary cases in group A appeared within seven days after the disease onset of index case in the same class. The incidence of EV infection remained low and was similar between the two groups eight days and beyond after the disease onset of index cases.Targeted class suspension for seven days with case isolation for seven days is an effective measure to mitigate transmission of EV infection in children.

Background Severe illness can occur in young children infected with certain types of enteroviruses including echovirus 11 (Echo11) and coxsackievirus B5 (CoxB5). The manifestations and outcomes of Echo11 and CoxB5 diseases across all ages of children remained not comprehensively characterized in Taiwan. Methods Culture-confirmed Echo11 (60 patients) or CoxB5 (65 patients) infections were identified in a hospital from 2010 to 2018. The demographics, clinical presentations, laboratory data and outcomes were abstracted and compared between the two viruses infections. Results Echo11 and CoxB5 was respectively identified in 7 (77.8%) and 2 (22.2%) of 9 calendar years. The median age of all patients was 15 months (range, 1 day–14.5 years). For infants ≤3 months old, Echo11 (23 cases) was associated with higher incidence of aseptic meningitis (35% versus 0%, P = 0.003), and a lower rate of upper respiratory tract infections (URI) (22% versus 65%, P = 0.004) compared to CoxB5 (20 cases) infections. For patients >3 months old, URI was the cardinal diagnosis (60%) for both viruses. Aseptic meningitis was also more commonly identified in elder children with Echo11 infections (27% versus 11%), though with marginal significance (P = 0.07). Acute liver failure was identified in four young infants with Echo11 infections including one neonate dying of severe sepsis and myocarditis. All patients with CoxB5 infections recovered uneventfully. Conclusion Aseptic meningitis, sepsis-like illness and acute liver failure were more commonly identified in children with Echo11 than those with CoxB5 infections, suggesting greater neurological tropism and virulence toward Echo11.

Older adults are subject to higher COVID-19 infection and mortality rates. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine have been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age, however, older adults were under-represented.A double-blind, randomized, multi-center study compared safety and immunogenicity of high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart in 420 participants of 65 years and older. The results have been stratified by the comorbidity status.Both high and mid-dose regimens elicited mostly mild adverse events and robust immune responses when measured as neutralizing and binding antibodies titers. High doses elicited better immune responses in the group without comorbidities.Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommend high dose for immunization of elder adults with MVC-COV1901. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04822025).

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially impacted human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2. Here, we demonstrated that acute SARS-CoV-2 infection elicits rapid and robust spike-binding and ACE2-blocking antibody responses, which wane approximately 11 months after infection. Serological responses were found to be correlated with the frequency of spike-specific memory B cell responses to natural infections. Further, significantly higher spike-binding, ACE2-blocking, and memory B cell responses were detected in patients with fever and pneumonia. Spike-specific antibody responses were found to be greatly affected by spike mutations in emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.ImportanceAs spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined the spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Further, the serological responses were correlated with the frequency of spike-specific memory B cell responses to natural infections. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. Moreover, the spike-specific antibody responses were substantially affected by the emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.

Background: Norovirus (NoV) and rotavirus (RV) are among the most common causes of acute gastroenteritis (AGE) of all ages worldwide. There have been scanty reports of the epidemiology data of NoV AGE from clinical virologic laboratory. Methods: All stool specimens sent to the virologic laboratory in a medical center in Taiwan for detection of both NoV (by reverse transcription-polymerase chain reaction) and RV (by enzyme immunoassay) from 2013 to 2018 were included for analysis. Results: A total of 15,991 specimens, annually ranging from 2430 in 2017–2915 in 2013, were included. 48.0% and 73.1% of the specimens were obtained from children aged

Moraxella catarrhalis is a common, potential pathogen colonizing the respiratory tract in children. However, there is little information regarding the determinants of M. catarrhalis colonization and disease development.A population-based cohort study was conducted to collect nasopharyngeal swabs from children aged 1, 2, 4, 6, 12, 18, 24, 36, and 60 months for the detection of four common respiratory tract pathogens, including Staphylococcus aureus, M. catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae. Questionnaires on breastfeeding status were administered during each visit.A total of 921 children were enrolled between 2012 and 2018. S.aureus was the most common pathogen, although the rates declined during the initial 18 months of life; in contrast, the other three pathogens increased during the first 5 years of life. M. catarrhalis was the second most common colonizing pathogen in all age groups, with prevalence ranging from 0.8% (7/842) at one month to 20.4% (33/162) at 60 months of age. Breastfed children (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.35-0.92; P = 0.02) had a lower potential for M. catarrhalis carriage; however, infants with a longer duration of exclusive breastfeeding (OR: 1.12; 95% CI: 1.01-1.25; P = 0.04), especially12 months of age, had a higher rate of M. catarrhalis carriage.Breastfeeding should be promoted because it may be correlated with a lower risk of M. catarrhalis carriage. However, an extended period of exclusive breastfeeding may be positively associated with M. catarrhalis colonization.

Background: This study aimed to assess the safety and immunogenicity of MVC-COV1901, a recombinant COVID-19 protein vaccine, containing S-2P protein adjuvanted with CpG 1018 and aluminum hydroxide, for people living with HIV (PWH). Methods: A total of 57 PWH of ≥20 years of age who are on stable antiretroviral therapy were compared with 882 HIV-negative participants. Participants received two doses of MVC-COV1901 28 days apart. Results: No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in PWH and comparators, respectively, 28 days after the second dose. After adjusting for sex, age, BMI category, and comorbidity, the adjusted GMT ratio of comparator/PWH was 3.2 (95% CI 2.5–4). A higher CD4/CD8 ratio was associated with a higher GMT (R = 0.27, p = 0.039). MVC-COV1901 has shown robust safety but elicited weaker immune responses in PWH. Conclusions: Further investigations may be needed to determine whether PWH require distinct immunization strategies with improved immunogenicity. The main study is registered at ClinicalTrials.gov (NCT04695652).

Echoviruses, for which there are currently no approved vaccines or drugs, are responsible for a range of human diseases, for example echovirus 11 (E11) is a major cause of serious neonatal morbidity and mortality. Decay-accelerating factor (DAF, also known as CD55) is an attachment receptor for E11. Here, we report the structure of the complex of E11 and the full-length ectodomain of DAF (short consensus repeats, SCRs, 1–4) at 3.1 Å determined by cryo-electron microscopy (cryo-EM). SCRs 3 and 4 of DAF interact with E11 at the southern rim of the canyon via the VP2 EF and VP3 BC loops. We also observe an unexpected interaction between the N-linked glycan (residue 95 of DAF) and the VP2 BC loop of E11. DAF is a receptor for at least 20 enteroviruses and we classify its binding patterns from reported DAF/virus complexes into two distinct positions and orientations, named as E6 and E11 poses. Whilst 60 DAF molecules can attach to the virion in the E6 pose, no more than 30 can attach to E11 due to steric restrictions. Analysis of the distinct modes of interaction and structure and sequence-based phylogenies suggests that the two modes evolved independently, with the E6 mode likely found earlier.

Background: Carriage of methicillin-resistant Staphylococcus aureus (MRSA) is associated with its transmission. International travels and massive gatherings may accelerate such transmission. MRSA carriage was surveyed among the attendees of two international medical conferences held in Taipei in 2010. Methods: A total of 209 attendees from 23 countries were recruited. Nasal specimens were collected from each volunteer and subjected to polymerase chain reaction (PCR) detection for MRSA. Molecular analysis, including pulsed-field gel electrophoresis, multilocus sequence typing (MLST), typing of staphylococcal cassette chromosome mec (SCCmec) and staphylococcal protein A (spa) genes, and detection of Panton-Valentine leukocidin (PVL) and sasX genes, was performed. Results: MRSA carriage was detected in 10 (4.8%) attendees from Vietnam (3/8, 37.5%), Korea (2/6, 33.3%), Japan (2/41, 4.9%), Philippines (2/52, 3.8%), and Bangladesh (1/4, 25.0%). The proportion of MRSA colonizers was significantly higher in the local hospital group compared to those from the other groups (3/17 vs. 7/192, p

Background Streptococcus pneumoniae infections in Taiwan mostly occur in children aged 2–4 years. Because of a significant increase in the incidence of serotype 19A-related infections, the 13-valent pneumococcal conjugate vaccine (PCV13) was initially introduced in the national immunization program for children 2–5 years of age, prior to the national programs for infants. We have assessed the impact of such vaccination programs in reducing the incidence of invasive pneumococcal disease (IPD) in Taiwanese children. Methods We analyzed the national data on IPDs from the Taiwan Centers for Disease Control between 2008 and 2017. We calculated the incidence rates of IPD and incidence rate ratios (IRRs) between years for different serotypes to estimate the effectiveness of the vaccination programs. Results The national catch-up primary vaccination schedule successfully reduced the incidence rate of IPD from 17.8/100 000 in 2012 to 5.5/100 000 in 2017 among children aged 0–5 years. The IRR (2017 over 2012) was 0.31, corresponding to a 69% reduction. A modest herd effect was also observed, with a 37% reduction in the incidence of IPD in elderly people (≥70 years) from 2012 to 2017. The incidence of IPD caused by serotype 19A in children aged 0–5 years was reduced by 32.6–44.3% yearly from 2012 to 2017. In 2015, serogroup 15 outnumbered 19A, to become the leading serotypes in children 0–5 years old. Conclusions Special catch-up vaccination programs starting from children 2–5 years of age with PCV13 have been highly effective in reducing the incidence of IPD, especially as caused by serotype 19A, in Taiwanese children.

Background/purpose: Staphylococcus aureus (S. aureus) causes diseases ranging from mild skin infections to invasive diseases. Carriage of S. aureus, including methicillin-resistant S. aureus (MRSA), is a significant risk factor for subsequent staphylococcal infection. Several studies discussed MRSA colonization in Taiwan, but mostly in northern Taiwan. This is the first study that estimates the prevalence of MRSA nasal colonization in healthy children and identifies the potential risk factors in central Taiwan. Methods: A total of 3144 healthy children aged 2–60 months who visited Taichung Veterans General Hospital (TCVGH) were screened for nasal S. aureus carriage from July 2005 to December 2010. Questionnaires included demographic information and potential risk factors for carriage of S. aureus were completed by parents/guardians. Results: Prevalence of MSSA and MRSA were 12.09% and 5.25%, respectively. The youngest group aged 2–6 months had the highest S. aureus carriage rate, and the carriage rate revealed a peak in summer. The nasal colonization of Streptococcus pneumoniae (S. pneumoniae) was a protective factor against S. aureus colonization. 85% of the MRSA colonizing isolates belonged to clonal complex 59/staphylococcal cassette chromosome type IV or VT, the local community clone in Taiwan. Conclusion: An increasing trend of MRSA nasal carriage rate in Taiwan had been brought forward, however, it was not observed in central Taiwan during the period of 2005–2010. We found a summer peak on both MRSA and MSSA carriages. Keywords: Central Taiwan, Children, Methicillin-resistant Staphylococcus aureus colonization

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been increasingly reported worldwide and are associated with nasal colonization. In Taiwan, available data disclosed a similar trend. We conducted a study for the updated childhood nasal MRSA carriage. Methods: From July 2005 to December 2010, children aged between 2 months and 5 years who presented for a well-child health care visit to a medical center or from kindergarten/daycare center were invited and a nasal swab specimen was obtained for the detection of MRSA. All MRSA isolates were characterized. Results: A total of 3226 children were included and the rate of nasal MRSA carriage was 10.2%. Children aged 2–6 months and >3 years were significantly associated with MRSA carriage, while pneumococcus colonization (p = 0.033) and breastfeeding (p = 0.025) were negatively associated with MRSA carriage. Of the 330 MRSA isolates, a total of 13 pulsotypes with two major patterns (type C, 47.0% and D, 29%) were identified. Most MRSA isolates belonged to two major clones, characterized as sequence type 59 (ST59)/pulsotype C/staphylococcal cassette chromosome (SCCmec) IV/Panton-Valentine leukocidin (PVL)-negative (45.8%) and ST59/pulsotype D/SCCmec VT/PVL-positive (22.7%). Two new clones as ST 508/SCCmec IV (9.7%) and ST573/SCCmec IV (7.3%) emerged and increased markedly since 2007. Conclusion: Between 2005 and 2010, 10.2% of healthy children in northern Taiwan carried MRSA in anterior nares, with the highest carriage rate for infants aged 2–6 months. Two emerging clones, ST 508 and ST 573, were identified and the clinical significance needs further surveillance. Keywords: Methicillin-resistant Staphylococcus aureus, Community-associated, Sequence type 59, Taiwan, Children, Colonization

Background Bacillus cereus is a well-known pathogen for self-limited foodborne illness, and rarely an opportunistic pathogen associated with invasive infections among immunocompromised patients. Nosocomial outbreaks have been rarely reported. Methods Between August and November 2019, four preterm neonates in neonatal care units of a medical center developed late-onset B. cereus bacteremia. An investigation was carried out. Forty-eight environmental specimens were obtained from these neonatal units, skin surface and environmental objects of Patient 4 for the detection of this organism 19 days after the onset of illness of Patient 4. B. cereus isolates from Patient 4, five unrelated patients and environmental objects if identified were further characterized by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results All four infants survived after vancomycin-containing treatment. Patient 4 developed diffuse cerebritis, brain abscess with severe neurologic sequelae. Of the 48 environmental samplings, 26 specimens showed positive for B. cereus, with one major clone (sequence type 365) accounting for 73%. The isolate from Patient 4 (ST427) was identical to one isolate collected from environmental objects in the same unit. After extensive cleaning of the environment and re-institution of the sterilization procedure of hospital linens, which was ceased since two months before the outbreak, no more cases was identified in these units for at least one year. Conclusions We documented a cluster of B. cereus bacteremia involving four preterm infants, which might be associated with cessation of the procedure for linen sterilization and was successfully controlled by re-institution of this procedure.

Background Mycoplasma pneumoniae is a major pathogen for community-acquired pneumonia and frequently causes outbreaks in children. M. pneumoniae-specific antibody response is detected upon acute infection and the serology is widely used in the clinical setting. Nevertheless, the cellular basis for antigen-specific antibody response to acute M. pneumoniae infection is largely undetermined in children. Methods Hospitalized children with community-acquired pneumonia were enrolled and the infection with M. pneumoniae was confirmed with positive PCR result and negative findings for other pathogens. The M. pneumoniae P1-specific antibody-secreting B cell (ASC) response was examined with the ex vivo enzyme-linked immunosorbent spot assay and the relationships between the ASC frequency and serological level and clinical parameters within M. pneumoniae patients were studied. Results A robust M. pneumoniae P1-specific ASC response was detected in the peripheral blood among M. pneumoniae-positive patients. By contrast, no M. pneumoniae-specific ASCs were detected among M. pneumoniae-negative patients. The IgM-secreting B cells are the predominant class and account for over 60% of total circulating M. pneumoniae-specific ASCs in the acute phase of illness. The M. pneumoniae P1-specific ASC frequency significantly correlated with the fever duration, and the IgG ASC frequency significantly correlated with serological titer among patients. Conclusion A rapid and potent elicitation of peripheral M. pneumoniae-specific ASC response to acute infection provides the cellular basis of antigen-specific humoral response and indicates the potential of cell-based diagnostic tool for acute M. pneumoniae infection. Our findings warrant further investigations into functional and molecular aspects of antibody immunity to M. pneumoniae.

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

The gastrointestinal tract is not the common infection site of Pseudomonas aeruginosa. The role of P. aeruginosa as a causative agent for diarrhea in children without preexisting disease is controversial.From 2003 to 2012, we reviewed the records of 259 diarrheal patients less than 5 years of age whose stool culture grew P. aeruginosa. Virulence phenotypes of bacterial isolates were determined in vitro, including cytotoxicity, penetration and adherence to epithelial cells.The presence of P. aeruginosa in children with diarrhea less than 5 years old is 0.91%. P. aeruginosa-associated diarrheal diseases were classified into 4 groups: Shanghai fever (enteric infection and sepsis) (5%), P. aeruginosa enterocolitis (15%), P. aeruginosa-related diarrhea (19%) and antibiotic-associated diarrhea (43%). The remaining patients had coinfection with other pathogens (18%). Shanghai fever was the most severe enteric disease with invasive infection and complications. The clinical features of P. aeruginosa enterocolitis were prolonged fever with bloody or mucoid diarrhea mimicking bacterial enterocolitis. The clinical features of P. aeruginosa-related diarrhea and antibiotic-associated diarrhea were similar to viral or toxin-mediated diarrhea. Compared with other P. aeruginosa-associated diarrheal diseases, patients with Shanghai fever were younger, usually infants, and the characteristic laboratory findings included leukopenia, thrombocytopenia, high C-reactive protein, hyponatremia and hyperglycemia. Except for Shanghai fever, antibiotic treatment is not recommended. Isolates from Shanghai fever were more cytotoxic and adherent than isolates from uncomplicated diarrheal patients.P. aeruginosa could be an enteric pathogen even in healthy children. Young age and highly virulent bacterial strains were risk factors for Shanghai fever.

Objectives Mycoplasma pneumoniae is currently the most commonly detected bacterial cause of childhood community-acquired pneumonia in several countries. Of note, clonal expansion of macrolide-resistant ST3 occurred in Japan and South Korea. An alarming surge in macrolide resistance complicates the treatment of pneumonia. We aimed to evaluate the clinical manifestation and clonal relatedness of M. pneumoniae circulating among children in Taiwan. Methods We prospectively enrolled 626 children with radiologically confirmed pneumonia between 2017 and 2019. An M. pneumoniae infection was suspected on clinical grounds, and tested by real-time PCR and oropharyngeal swab cultures. We used multilocus sequence typing and whole-genome sequencing to characterize the genetic features of M. pneumoniae. Results A total of 226 children with M. pneumoniae pneumonia were enrolled. Macrolide resistance was found in 77% (174/226) of patients. Multi-locus sequence typing revealed that ST3 (n = 93) and its single-locus variant ST17 (n = 84) were the predominant clones among macrolide-resistant strains. ST17 presented clinical characteristics comparable to its ancestor ST3. On multivariate analysis, macrolide resistance (OR 3.5; 95% CI 1.4–8.5; p 0.007) was independently associated with fever >72 hours after macrolide treatment. By whole-genome sequencing, prediction analysis of recombination sites revealed one recombination site in ST3 and ST17 compared with M29 (a macrolide-sensitive ST3 strain isolated from China in 2005) containing cytadhesin MgpC-like protein, RepMP4 and RepMP5. ST17 had another recombination site containing an adhesin and RepMP2/3. Conclusions In addition to macrolide resistance, ST3 and its ST17 variant might evolve through recombination between repetitive sequences and non-P1 cytadhesins for persistent circulation in Taiwan.

Enterovirus 71 (EV71) is one of the major pathogens that cause severe enteroviral infections. Our aim was to study the behavioral and household risk factors for its serious complications.Between May 2011 and November 2012, we enrolled children who had symptoms of EV71 infection from six hospitals in Taiwan. The caregivers of each patient were interviewed to determine their hand hygiene habits in relation to EV71 infection. The severity of EV71 infection was classified as follows: Stage 1, hand-foot-mouth disease or herpangina; Stage 2, meningitis or myoclonic jerk; Stage 3A, encephalitis; Stage 3B, cardiopulmonary failure. Stages 2 to 3B were defined as severe EV71 infection. Children with Stages 3A and 3B infection were designated as the critical group.A total of 399 patients had laboratory-confirmed EV71 infection. Three risks factors were associated with the different degrees of severity in EV71 infection. Children2 years old had much greater risks for severe EV71 infection [odds ratio (OR) 1.8; 95% confidence interval (CI), 1.2-2.8], delayed medical evaluation for critical infection (OR 9.4; 95% CI, 3.6-24.1), and developmental retardation for cardiopulmonary failure (OR 8.3; 95% CI, 2.0-33.7). Among all the habits and household factors, caregivers in the critical group had a significantly lower rate in terms of cleaning the faucet after washing their hands (OR 2.63; 95% CI, 1.14-6.08).Children2 years old, developmental retardation, and delayed medical intervention were associated with severe EV71 infection. Cleaning water faucets after hand washing was a protective habit that reduced the risk of complications.

Background During recent 20 years, enterovirus 71 (EV71) has emerged as a major concern among children, particularly in the Asia-Pacific region. To understand current EV71 serostatus, to find risk factors associated with EV71 infection and to establish future EV71 vaccine policy, we performed a seroepidemiology study in Taiwan in 2017. Methods After informed consent was obtained, we enrolled preschool children, 6–15-year-old students, 16–50-year-old people. They received a questionnaire and a blood sample was collected to measure the EV71 neutralization antibody. Results Altogether, 920 subjects were enrolled with a male-to-female ratio of 1.03. The EV71 seropositive rate was 10% (8/82) in infants, 4% (6/153) in 1-year-old children, 8% (7/83) in 2-year-old children, 8% (13/156) in 3–5-year-old children, 31% (38/122) in 6–11-year-old primary school students, 45% (54/121) in 12–15-year-old high school students and 75% (152/203) in 16-50-year-old people. Risk factors associated with EV71 seropositivity in preschool children were female gender, having siblings, more siblings, and contact with herpangina or hand-foot-and-mouth disease. The risk factor with EV71 seropositivity in 16–50-year-old people was having children in their families in addition to older age (p

Background Cervical lymphadenopathy is among the cardinal manifestations of Kikuchi disease (KD). The incidences and locations of extra-cervical lymph nodes (LNs) involvement in KD have not been comprehensively reported. Methods From 2003 to 2016, 60 patients with pathologically confirmed KD and with computed tomography and/or whole-body inflammation scans at diagnosis were retrospectively identified. The locations, sizes and characteristics of all affected LNs were analyzed by extensive review of the image studies. The clinical and laboratory parameters were abstracted from medical records and the associations with extra-cervical LNs involvement were identified. Results Female accounted for 35 (58.3%) patients and the median age of all patients was 21.3 years (ranges, 3–64 years). Of 59 patients with evaluable neck images, 42 (71.2%) and 16 (27.1%) patients presented with unilateral and bilateral nodal involvement, respectively, with the most common locations at level II, III and IV by Som's classification. The largest LNs appeared most commonly in level II. The incidences of extra-cervical lymphadenopathy in abdomen, pelvis, inguina, axilla and mediastinum with available images were respectively 52.9% (9/17), 47.1% (8/17), 41.2% (7/17), 30.6% (11/36) and 14.3% (8/56). When compared to cases with solitary cervical lymphadenopathy, the cases with extra-cervical lymphadenopathy had significantly greater incidences of bilateral cervical lymphadenopathy (P = .0379) and leukopenia (P = .0173). Conclusion Unilateral cervical lymphadenopathy was the most frequent form of LNs involvement of KD. Extra-cervical lymphadenopathy was not uncommon and was associated with the appearance of bilateral distribution of cervical LNs and leukopenia.

An outbreak of the hand-foot-mouth disease with severe neurological cases, mainly caused by the genotype C1 enterovirus A71 (EV-A71), occurred in Taiwan between 2018 and early 2019. In the recent decade, the most dominant EV-A71 genotypes in Taiwan were B5 and C4 but changed to C1 in 2018. Antibody-mediated immunity plays a key role in limiting the EV-A71 illness in humans. However, the level of neutralizing activities against genotype C1 virus by human polyclonal and monoclonal antibodies (MAbs) remains largely unclear. In the study, we demonstrated that that 39% (9 in 23) of post-infection sera from the genotype B5- or C4-infected patients in 2014–2017 exhibit reduced titers with the 2018–2019 genotype C1 viruses than with the earlier B5 and C4 viruses tested. This finding with polyclonal sera is confirmed with human MAbs derived from genotype B5 virus-infected individuals. The 2018–2019 genotype C1 virus is resistant to the majority of canyon-targeting human MAbs, which may be associated with the residue change near or at the bottom of the canyon region on the viral capsid. The remaining three antibodies (16-2-11B, 16-3-4D, and 17-1-12A), which target VP1 S241 on the 5-fold vertex, VP3 E81 on the 3-fold plateau and VP2 D84 on the 2-fold plateau of genotype C1 viral capsid, respectively, retained neutralizing activities with variable potencies. These neutralizing antibodies were also found to be protective against a lethal challenge of the 2018–2019 genotype C1 virus in an hSCARB2-transgenic mice model. These results indicate that the EV-A71-specific antibody response may consist of a fraction of poorly neutralizing antibodies against 2018–2019 genotype C1 viruses among a subset of previously infected individuals. Epitope mapping of protective antibodies that recognize the emerging genotype C1 virus has implications for anti-EV-A71 MAbs and the vaccine field., Author summary EV-A71 is a cause of hand-foot-mouth disease, epidemics of which still regularly occur around the globe. Given that EV-A71 immune protection from the disease correlates with neutralizing antibody responses, but the responses in humans prior to an outbreak are still poorly understood. An outbreak of hand-foot-mouth disease among children emerged in Taiwan from 2018 to 2019, and genotype C1 EV-A71 caused most of the cases. Here, we characterized EV-A71-neutralizing antibody profiles in details at both the serological and monoclonal levels and showed that antibodies generated by humans prior to the emergence of genotype C1 EV-A71 less effectively neutralize C1 compared to the prior circulating genotypes, which implies the presence of antigenic variation in the EV-A71 genotypes. We further identified and mapped critical neutralizing epitopes of 2018–2019 genotype C1 EV-A71 on the top and margin of the viral capsid pentamer and demonstrated the in vivo protective effect of human monoclonal antibodies, which highlight the properties of human antibody-neutralizing sites on EV-A71 and the potential of human antibodies as antiviral agents.

Prompt diagnosis of an oseltamivir-resistant marker is important for patient management, in particular to prevent the spread of resistant strains in the recent human H7N9 outbreak. We tailored a pyrosequencing assay to reveal neuraminidase R292K, a resistant marker found in one isolate from China, and demonstrated its performance in both sensitivity and specificity. In addition, a semi-nested polymerase chain reaction was applied, which enhanced the detection rate by at least 10-fold. We validated this assay by examining the marker in Taiwan's first imported human case and found R and K in quasispecies.

The benefits of intravenous immunoglobulin (IVIG) therapy for severe neonatal enterovirus infections are still controversial.To evaluate whether timing of IVIG administration might affect clinical outcomes of neonates with severe enteroviral infections.We retrospectively analyzed 67 neonates with culture-confirmed severe enteroviral infection, defined as hepatitis with coagulopathy and thrombocytopenia. Clinical features, outcomes and the usage of IVIG therapy were collected and analyzed. IVIG administered within 3 days of illness onset was classified as early IVIG therapy.Of the 67 cases, 38 (57%) were male, 27 (40%) were premature, 57 (85%) had disease onset within 7 days of life and all but 2 cases were caused by coxsackievirus B group. Ten infants (15%) had clinically evident myocarditis. 41 infants (61%) received IVIG therapy and 29 were early IVIG therapy. Fifteen infants (22%) eventually died, without IVIG therapy for 7 infants. The deceased had a significantly higher peak serum aspartate aminotransferase (AST) level than the survivors (3539 vs. 866 IU/L, p0.01). The timing of IVIG therapy was highly correlated with the timing of peak AST level in patients with early IVIG therapy. Multiple logistic regression analysis showed that a higher nadir hemoglobin level (adjusted odds ratio 2.8, 95% confidence interval: 1.4-5.4), no concurrent myocarditis (42.6 [3.4-5289]) and early IVIG therapy (14.7 [1.3-163]) were independently associated with a favorable prognosis.In defined severe neonatal enterovirus infections, serum AST level correlated with the disease severity. Early IVIG therapy, if needed, may be beneficial for survival.

Background Enterovirus 71 (EV71) remains a leading pathogen for acute infectious diseases in children, especially in Asia. The cellular basis for establishing a virus-specific antibody response to acute EV71 infections is unclear in children. Methods We studied the magnitude of virus-specific antibody-secreting B cells (ASCs) and its relationship with serological response, clinical parameters, and virological parameters among children with laboratory-confirmed EV71 infection. Results A potent EV71 genogroup B- and virus-specific ASC response was detected in the first week of illness among genotype B5 EV71-infected children. The cross-reactive EV71-specific ASC response to genogroup C viral antigens composed about 10% of the response. The EV71-specific ASC response in children aged ≥3 years produced immunoglobulin G predominantly, but immunoglobulin M was predominant in younger children. Proliferation marker was expressed by the majority of circulating ASCs in the acute phase of EV71 infection. Virus-specific ASC responses significantly correlated with throat viral load, fever duration, and serological genogroup-specific neutralization titer. Conclusions The presence of a virus-specific ASC response serves an early cellular marker of an EV71-specific antibody response. Further detailed study of EV71-specific ASCs at the monoclonal level is crucial to delineate the specificity and function of antibody immunity in children.

Background: A resurgence of mumps was noted recently and outbreaks were increasingly reported in populations with high vaccine coverage. We aimed to evaluate the seroprevalence to mumps in Taiwan, where a two-dose childhood mumps-containing vaccine program, with a high coverage rate, had been implemented for >20 years. Methods: The anti-mumps IgG was determined in 3552 participants of all ages in Taiwan. The age-specific seropositivity rates were calculated and the sociodemographic variables associated with the seronegative sera were analyzed with a logistic regression method. Results: The overall seroprevalence to mumps was 71%, with a higher rate in adults ≥19 years old than in the pediatric population

BackgroundUrinary tract infection (UTI) caused by resistant bacteria is becoming more prevalent. Few studies are available regarding community-onset UTIs caused by extended-spectrum β-lactamase (ESBL)-producing bacteria in children.Materials and methodsDuring a 5-year period, hospitalized children with community-onset UTI caused by ESBL-producing Escherichia coli (case) and those with non-ESBL-producing E. coli (control) were identified. Patients with long-term care facility stay within the preceding month and those with urine cultures obtained >72 hours after admission were excluded. Clinical features and risk factors associated with the occurrence of ESBL-producing E. coli UTI were reviewed.ResultsThe prevalence of UTI due to ESBL-producing E. coli increased slightly from 0.59% in 2002 to 0.96% in 2006. A total of 104 cases and 208 controls were included for comparison. The ciprofloxacin resistance of the ESBL-producing E. coli increased significantly in this period (p = 0.006). Pre-existing neurological diseases (p

Purpose Viral etiology of bronchiolitis in children in Taiwan has been fragmentary. We conducted a prospective study to figure out the viral epidemiology of bronchiolitis in Taiwan. Materials and methods From January 2009 to March 2011, a total of 113 children with bronchiolitis, aged

Background/Purpose(s) To explore the clinical features of different human metapneumovirus (hMPV) genotypes/genogroups in hospitalized children. Methods From January 2005 to April 2010, 3313 children's respiratory specimens sent for the detection of respiratory syncytial virus antigen were also tested for hMPV by real time-polymerase chain reaction. Demographics, clinical presentations, and laboratory findings of patients infected with different genotypes/genogroups of hMPV were compared. Results A total of 725 samples were positive for hMPV (positive rate, 23%). The F gene was sequenced for 279 isolates; of these, genotype A was identified in 51% (A1, 6.1%; A2, 45%) and genotype B in 49% (B1, 19%; B2, 30%). Medical records of 152 hospitalized children were reviewed. Co-infection with other pathogens was 25.7% (39/152). Excluding co-pathogens other than respiratory syncytial virus, a total of 124 children were analyzed. The most common symptoms included cough, fever, rhinorrhea, wheezing and respiratory distress with accessory muscle usage. The main diagnosis was bronchiolitis. The most common chest radiographic findings were increased perihilar infiltrates. No significant difference was found in terms of demographics, clinical manifestations, and laboratory findings among the children infected with different serogroups of hMPV. Conclusion hMPV accounted for a substantial proportion of hospitalized children with lower respiratory tract infection with a high co-infection rate. The A2 subgroup was the most frequently observed, followed by B2. No significant difference was found among patients infected with different genotypes/genogroups of hMPV in terms of clinical manifestations.

BACKGROUND The Streptococcus pneumoniae serotype 19A sequence type (ST) 320 clone, derived from an international Taiwan(19F)-14 (ST236) clone, has become prevalent in many countries. METHODS The dynamics of invasive pneumococcal disease (IPD) were determined using the database of the National Notifiable Disease Surveillance System in Taiwan. The virulence of 19A ST320 and Taiwan(19F)-14 (ST236) were assessed in mice. By constructing an isogenic serotype 19F variant of the 19A ST320 strain (19F ST320), we analyzed the role of capsular type and genetic background on the difference in virulence between 19A ST320 and Taiwan(19F)-14 (ST236). RESULTS Between 2008 and 2011, IPD due to serotype 19A increased from 2.1 to 10.2 cases per 100 000 population (P < .001); IPD due to any serotype also significantly increased (P = .01). Most serotype 19A isolates belonged to ST320. Using competition experiments in a murine model of colonization, we demonstrated that 19A ST320 outcompeted Taiwan(19F)-14 (ST236; competitive index, 20.3; P = .001). 19F ST320 was 2-fold less competitive than the 19A ST320 parent (competitive index, 0.47; P = .04) but remained 14-fold more competitive than Taiwan(19F)-14 (ST236; competitive index, 14.7; P < .001). CONCLUSIONS Genetic evolution of pneumococcal clones from Taiwan(19F)-14 (ST236) to 19A ST320 has made this pneumococcus better able to colonize of the nasopharynx. This evolution reflects not only a switch in capsular serotype but also changes in other loci.

Human enterovirus 71 (HEV71) infections are a significant public health threat in the Asia-Pacific region and occasionally cause severe neurological complications and even death in children. Although good hand hygiene is important for controlling infection, relevant data regarding the efficacy of widely used hand disinfectants against HEV71 are still lacking.To investigate the virucidal activity of alcohols and alcohol-based hand disinfectants against HEV71.A common alcohol-based hand disinfectant (0.5% chlorhexidine gluconate + 70% isopropanol) as well as different concentrations of isopropanol and ethanol were tested for virucidal activity against HEV71 using the suspension and the fingerpad tests.In suspension tests, 85% and 95% ethanol achieved a mean log10 reduction factor in HEV71 titre of3 and nearly 6, respectively, within 10 min. By contrast, 70% and 75% ethanol and any concentration of isopropanol (70-95%) produced a factor of1 in this test after the same exposure time. In fingerpad tests, only 95% ethanol showed a mean log10 reduction factor of4, while both 75% ethanol and a chlorhexidine gluconate-containing formula were ineffective against HEV71 with a mean log10 reduction factor of1 after a 30 s exposure time.Widely used alcohol-based hand disinfectants based on 70% ethanol or isopropanol have poor effectiveness against HEV71. Ninety-five percent ethanol is the most effective concentration, but still cannot fully inactivate HEV71 and may be impractical for use in many instances. Hand hygiene with alcohol-based hand disinfectants alone is not recommended for preventing HEV71 transmission.

The aim of this study was to estimate the prevalence of macrolide-resistant Mycoplasma pneumoniae in Taiwan and to compare the clinical courses of pediatric patients with macrolide-resistant (MR) M. pneumoniae and macrolide-susceptible (MS) M. pneumoniae infection. Patients were among the children admitted to Chang Gung Children's Hospital with mycoplasmal pneumonia between February and December 2011. Detection for macrolide resistance was performed after informed consent was obtained. We retrospectively reviewed medical records and compared the clinical courses of two groups of patients of 73 children enrolled into our study. The rate of macrolide resistance in M. pneumoniae was 12.3 %. Longer hospital stay was observed in the MR patients than MS patients [median, 7 days vs. 5 days (P = 0.019)]. Clinical features or radiographic or laboratory findings are not helpful to differentiate MR from MS mycoplasmal pneumonia. Early diagnosis of MR mycoplasmal pneumonia is crucial for the best management of these patients and obviates the need for extensive etiological searches of these nonresponding cases.

Traditional methods for detection and serotyping of enterovirus infections are virus isolation and immunofluorescence assay (VI-IFA), which are labor-intensive and time-consuming. Recently, VP1 gene has been targeted to develop a CODEHOP-based RT-PCR (VP1-CODEHOP) for the same purpose. In this study, we conducted a 5-year enterovirus surveillance comparing the VI-IFA and VP1-CODEHOP tests. Throat swabs were collected from 431 pediatric patients and 208(48%) and 250(58%) were tested positive by the VI-IFA and VP1-CODEHOP tests, respectively. Among the 47 cases who had inconsistent results between the VI-IFA and VP1-CODEHOP tests and provided paired sera for serological verifications, correct diagnosis for the VI-IFA and VP1-CODEHOP were 5(11%) and 40(85%) cases, respectively. Therefore, the VP1-CODEHOP is more reliable for detection of human enteroviruses than the VI-IFA. Based on serological verifications for the eight cases who had inconsistent serotypes between the two tests and provided paired sera, five and two showed consistent serotypes with the VP1-CODEHOP and VI-IFA tests, respectively. CVA16, CVA6 and EV71 were the most prevalent serotypes in northern Taiwan, 2008~2012. Moreover, variant CVA2, CVA6 and EV71 viruses were further identified based on phylogenetic analysis of partial VP1 sequences. In conclusion, the VP1-CODEHOP test could be used as the primary method for enterovirus surveillance to support decision-making for outbreak control.

Background Antibodies play a major role in the protection against influenza virus in human. However, the antibody level is usually short-lived and the cellular mechanisms underlying influenza virus-specific antibody response to acute infection remain unclear. Methods We studied the kinetics and magnitude of influenza virus-specific B-cell and serum antibody responses in relation to virus replication during the course of influenza infection in healthy adult volunteers who were previously seronegative and experimentally infected with seasonal influenza H1N1 A/Brisbane/59/07 virus. Results Our data demonstrated a robust expansion of the virus-specific antibody-secreting cells (ASCs) and memory B cells in the peripheral blood, which correlated with both the throat viral load and the duration of viral shedding. The ASC response was obviously detected on day 7 post-infection when the virus was completely cleared from nasal samples, and serum hemagglutination-inhibition antibodies were still undetectable. On day 28 postinfection, influenza virus-specific B cells were further identified from the circulating compartment of isotype-switched B cells. Conclusions Virus-specific ASCs could be the earliest marker of B-cell response to a new flu virus infection, such as H7N9 in humans.

BACKGROUND For the scarcity of data, we investigated the vaccine effectiveness (VE) of the combined use of pneumococcal conjugate vaccines (PCVs) of different valences against invasive pneumococcal disease (IPD) in children. METHODS We conducted a matched case-control study using the national IPD surveillance database and the national vaccination registry. Four age-matched, gender-matched and neighborhood-matched controls were identified for each incident IPD case ≦5 years with disease onsets between October 2007 and December 2013. Conditional logistic regression was used to assess VE against all serotype and serotype 19A IPD. RESULTS In 523 cases (median age: 28.5 months; range: 2.0-69.4 months) and 2086 controls (28.7; 2.2-70.1), a similar VE against all-serotype IPD was found between PCV13 (76%; 61-85%) and combined 7-valent PCV (PCV7)/10-valent PCV (PCV10) plus PCV13 (78%; 56-89%). The VE for PCV7/PCV10 was slightly lower (48%; 32-60%). Regarding serotype 19A, a significantly reduced risk was observed for both PCV13 (82%; 63-91%) and combined PCV7/PCV10 plus PCV13 (87%; 61-96%). PCV7/PCV10 had only a borderline protective association (31%; 4-51%). For children receiving PCV13 alone, VE against all-serotype IPD did not differ between starting the dosing at ≥2 (78%; 56-89%) or

Pneumonia is the leading reason for hospitalization in children. The heptavalent pneumococcal conjugate vaccine was introduced in Taiwan in October 2005. There has been no comprehensive study of the etiology of childhood community-acquired pneumonia (CAP), either in the pre- or postpneumococcal conjugate vaccine era, in Taiwan.From August 2001 to July 2002, consecutive children admitted to a teaching hospital with radiologically confirmed CAP were prospectively enrolled. The following were considered indicative of infection when positive: blood or pleural effusion bacterial culture or urinary Streptococcus pneumoniae antigen test (Binax NOW), direct immunofluorescent antigen test for Chlamydia species and viruses, virus isolation and identification and viral, mycoplasmal or chlamydial serologic tests.A total of 209 children were included, and 102 children (48.8%) were male. Patients' ages ranged from 7 months to 16 years with a median of 4 years and 3 months. The combined tests identified at least 1 etiologic agent in 85.6% of all cases, including typical bacterial pathogens in 88 cases (42.1%; 86 S. pneumoniae, 1 methicillin-resistant Staphylococcus aureus and 1 Mycobacterium tuberculosis), Mycoplasma pneumoniae in 77 cases (36.8%), Chlamydia species in 24 cases (11.5%), viral etiology in 86 cases (41.1%) and mixed viral-bacterial infections in 69 cases (33%). Children with S. pneumoniae infection were significantly younger than those with Mycoplasma pneumoniae infection (P = 0.0055) or unknown etiology (P = 0.0140).S. pneumoniae, Mycoplasma pneumoniae and viruses were equally common etiologic agents of childhood CAP in Taiwan. Frequent coinfection increased the difficulty of both predicting the responsible organisms and choosing empiric antibiotics for the management of pediatric CAP.

To evaluate the population immunity to measles in Taiwan where the coverage rate of the measles vaccine was95% for more than a decade, anti-measles IgG was determined in 3552 Taiwanese volunteers in 2007. The overall seroprevalence was 74.7% (95% confidence interval [CI]: 73.3-76.1%). In subgroups aged 2-25 years, to whom at least 2 doses of measles-containing vaccine were given, there was a declining trend of seropositivity with age from 94.5% at 2 years to 50.6% at 21-25 years (p0.0001). Age (odds ratio [OR]: 1.0464, 95% CI: 1.043-1.085) and male gender (OR: 1.466, 95% CI: 1.131-1.901) were independent factors predicting seronegative sera in this population. Seroprevalence was uniformly95% in the older population (≥ 35 years) who had not been immunized against measles. The waning vaccine-induced immunity may have impact on the control of measles in the future, especially when the vaccinated population becomes older.

Multi-drug-resistant organisms are increasingly recognized as a global public health issue. Healthcare-associated infection and antimicrobial resistance are also current challenges to the treatment of infectious diseases in Taiwan. Government health policies and the health care systems play a crucial role in determining the efficacy of interventions to contain antimicrobial resistance. National commitment to understand and address the problem is prerequisite. We analyzed and reviewed the antibiotic resistance related policies in Taiwan, USA, WHO and draft antimicrobial stewardship program to control effectively antibiotic resistance and spreading in Taiwan. Antimicrobial stewardship program in Taiwan includes establishment of national inter-sectoral antimicrobial stewardship task force, implementing antimicrobial-resistance management strategies, surveillance of HAI and antimicrobial resistance, conducting hospital infection control, enforcement of appropriate regulations and audit of antimicrobial use through hospital accreditation, inspection and national health insurance payment system. No action today, no cure tomorrow. Taiwan CDC would take a multifaceted, evidence-based approach and make every effort to combat antimicrobial resistance with stakeholders to limit the spread of multi-drug resistant strains and to reduce the generation of antibiotic resistant bacteria in Taiwan.

Immunogenicity and safety of 13-valent and 7-valent pneumococcal conjugate vaccines (PCV13; PCV7) were compared in Taiwanese children. In this double-blind, multicenter study, healthy children were randomly assigned to receive PCV13 ( n = 84) or PCV7 ( n = 84) at 2, 4, 6 and 15 months with routine pediatric vaccines. For the 7 PCV13/PCV7 common serotypes, serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) were high 1 month postinfant series, with ≥95.0% in both groups achieving IgG levels ≥0.35 μg/mL, with a trend to lower IgG GMCs for PCV13 compared with PCV7 (PCV13:PCV7 GMC ratios 0.59–0.91). For the 6 additional serotypes unique to PCV13, GMCs were notably higher after PCV13 than PCV7 (PCV13:PCV7 GMC ratios 1.50–202.58). Immune responses generally increased posttoddler dose. Safety was similar between groups. PCV13 was safe and immunogenic in this Taiwanese population. PCV13 should offer broader protection than PCV7 against pneumococcal disease. Clinical trials registration number: NCT00688870

Background. Influenza A is a major pathogen of humans and has the potential to cause worldwide pandemics. Natural killer (NK) cells are important effector cells in the innate immune response against viruses, including influenza A. Infants are more susceptible to severe influenza A viral infection, possibly attributed in part to their defective NK function. Methods. We compared the NK responses to influenza using umbilical cord blood (UCB) and adult peripheral blood (APB) mononuclear cells and purified NK cells. Results. Influenza A induced dose-dependent apoptosis of NK cells with down-regulation of NKp46 expression, which was more pronounced in UCB. Both UCB and APB NK cells responded to influenza infection by up-regulating CD69 and CD107a expression, a process further enhanced by interleukin (IL) 15. Influenza exposure also down-regulated perforin expression and K562 cytotoxicity in UCB NK cells, which was partially restored by IL-15. The production of interferon (IFN)c and tumor necrosis factor (TNF)a by NK cells in responding to influenza was further enhanced by IL-15. Conclusions. Our findings show differential NK responses between newborns and adults. IL-15 may be beneficial in combating influenza by enhancing cytotoxic function and IFN-c production.

Severe necrotizing pneumococcal pneumonia may progress to the development of bronchopleural fistula (BPF). The purpose of this study was to describe the clinical courses and identify risk factors for the development of bronchopleural fistula in children with pneumococcal pneumonia. Histopathologic features of children receiving surgical resections of the lung because of BPF were analyzed to explore the pathogenesis of destructive lung disease caused by Streptococcus pneumoniae.A total of 112 cases of culture-proven pneumococcal pneumonia were identified between January 2001 and March 2010 at Chang Gung Children's Hospital. The medical charts of all cases of culture-proven pneumococcal pneumonia were reviewed.Pneumococcal pneumonia in 18 children (18/112, 16.1%) was complicated by BPF. As compared with children without BPF, children with BPF had significantly lower white blood cell counts at admission (P = 0.03) and significantly longer durations of fever and hospitalization (P0.001). Multivariate analysis revealed that acute respiratory failure (odds ratio = 8.9; 95% confidence interval = 2.6-30.9; P = 0.001) and serotype 19A infection (odds ratio = 5.0; 95% confidence interval = 1.2-22.1; P = 0.03) were risk factors for the development of BPF. Histopathologic analyses were available for 12 children who underwent surgical resections of the lung. Coagulative necrosis with pulmonary infarction was found in 11 of the 12 cases.Serotype 19A was strongly associated with BPF. Vaccines containing this serotype will be important for prevention.

Background Staphylococcus aureus is the major nosocomial pathogen and rapid detection of colonized patients with subsequent precaution is needed to prevent transmission. A new assay, the BD GeneOhm™ SaphSR assay (BD GeneOhm™, San Diego, CA, USA), is a multiplex real-time polymerase chain reaction (PCR) for rapid detection of both methicillin-sensitive S aureus (MSSA) as well as methicillin-resistant S aureus (MRSA). Methods Anterior nasal swab specimens of 273 pediatric and adult patients hospitalized in intensive care units at Chang Gung Memorial Hospital were collected for this assay in parallel with conventional cultures as standard. Results Overall, 71 (26.0%) patients were colonized with S aureus by conventional culture and MRSA accounted for 67.6% of all isolates. For the detection of MRSA, 79 patients (28.9%) were positive by PCR and 48 (17.6%) were positive by conventional cultures. The sensitivity, specificity, and positive and negative predictive values were 95.9%, 85.3%, 58.5%, 99.0%, respectively. For the detection of MSSA, 48 patients (17.6%) were positive by PCR and 23 (8.4%) were positive by conventional culture. The sensitivity, specificity, and positive and negative predictive values were 91.3%, 89.2%, 43.8%, and 99.1%, respectively. Conclusion As a screening method, the BD GeneOhm™ StaphSR assay could rapidly detect and differentiate between MRSA and MSSA colonization. A negative result of the assay could almost exclude S aureus colonization.

Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) species complicates the use of antibiotics if indicated. We investigated the impact of antimicrobial resistance on clinical outcomes and discussed how to use antibiotics rationally. Hospitalized children in 2005–2006 with stool cultures positive for NTS were identified. The clinical and microbiological features were retrospectively reviewed. A total of 683 children were included [371 (54.3%) male; 89.5%

BACKGROUND/PURPOSE: There have been many reported cases of Listeria monocytogenes bacteremia in Europe and the United States, but only a few from Taiwan. The present study was undertaken to analyze the clinical characteristics of patients with L. monocytogenes bacteremia in Taiwan. METHODS: Patients with culture-confirmed L. monocytogenes bacteremia were identified at Chang Gung Memorial Hospital between January 2001 and December 2008. The clinical features and outcomes of the patients and the antimicrobial susceptibilities of the clinical isolates were analyzed. RESULTS: Forty-three patients, including two newborn babies (4.7%) and 41 adults (95.3%), with at least one episode of Listeria bacteremia were identified. Forty-two (97.7%) of these patients had underlying diseases. Thirty-three patients (76.7%) had fever, 14 (32.6%) had experienced respiratory distress, and 11 (25.6%) had reported changes in consciousness. Twelve patients died within 14 days of infection, corresponding to a case-fatality rate of 27.9%. All the clinical isolates tested were susceptible to ampicillin, penicillin and vancomycin. CONCLUSION: Most cases of L. monocytogenes infection occurred in adults with underlying diseases, especially malignancy, and only two cases of neonatal L. monocytogenes bacteremia were identified over the 8-year period. Penicillin, ampicillin and vancomycin could be used for the treatment of L. monocytogenes bacteremia, with the case-fatality rate lower for patients who received appropriate treatment.

Invasive pneumococcal disease (IPD) burden is significant in the Asia-Pacific region. This review describes the epidemiology and Streptococcus pneumoniae (SP) serotype distribution of IPD in children in the Asia-Pacific region from studies published from 1999 to 2010. IPD incidence varies widely in Asia-Pacific countries depending on the method of surveillance, the population studied, and the time period. Incidences are highest for younger children, with rates near 100-200 cases per 100,000 children aged1 or 2 years. Incidences of preventable disease are estimated to be 6-200 cases per 100,000. Heptavalent pneumococcal conjugate vaccine (PCV7) serotype coverage shows a very wide range over the Asia-Pacific region. Ten countries have high vaccine serotype coverage (70%), and six countries have low vaccine serotype coverage (50%). The majority of SP serotypes in children with IPD in most countries in the Asia-Pacific region are susceptible to penicillin (intermediate and resistant50%); a few countries have SP serotypes with high level resistance to penicillin (intermediate and resistant50%). Japan, Taiwan, and Thailand have high PCV7 serotype coverage. Countries with low pneumococcal resistance to antimicrobials have shown increasingly higher nonsusceptibility with time. National vaccination programmes that include PCV7, 10-valent pneumococcal conjugate vaccine (PCV), or 13-valent PCV would significantly affect IPD burden in children aged5 years in the Asia-Pacific region, as well as the burden of penicillin-nonsusceptible IPD.

Clinical features of echovirus 6 and 9 infections in children have not been comprehensively evaluated, particularly for sporadic cases.To describe the clinical features of children with echovirus 6 or 9 infections.From 2000 to 2008, 199 children with culture-proven echovirus 6 or 9 infections identified in a university-affiliated hospital were included. Data extracted from 174 inpatients were further analyzed.Age ranged from 4 days to 15 years with a mean of 4.7 years. 123 (62%) were male. The disease spectrums were similar for echovirus 6 (n=100) and 9 (n=74) infections, with aseptic meningitis (49% and 51%, respectively) being the most common syndrome, followed by meningismus, upper respiratory tract infection, pneumonia, and herpangina. All 174 inpatients had fever but the duration of fever was significantly longer in patient with echovirus 9 infection than those with echovirus 6 infections (6.0 days vs. 3.8 days, p0.001). The rate of leukocytosis (leukocyte count15,000/μL) were significantly higher in patients with echovirus 6 infections than those with echovirus 9 infection (p0.001). One neonate with echovirus 6 infection died from hepatic necrosis with coagulopathy, and one infant with echovirus 6 infection and one child with echovirus 9 infection died from brain involvement. Two children had long-term sequelae of seizure disorder. The remaining 169 children (97%) recovered uneventfully.For children with echovirus 6 or 9 infections requiring hospitalization, aseptic meningitis was the most common manifestation and fatal outcome or long-term sequel, though rare, might occur.

The 2009 pandemic influenza A (H1N1) has caused significant morbidity and mortality around the world. Safety and immunogenicity studies of 2009 pandemic influenza A (H1N1) virus in children and adolescents are limited. In this prospective, open-label study, 2 doses of a monovalent, unadjuvanted, inactivated, split-virus 2009 pandemic influenza virus A (H1N1) vaccine (AdimFlu-S) were administered to 183 healthy children and adolescents aged 1-17 years. Adverse reactions were assessed, and hemagglutination inhibition antibody titers were determined. Three weeks after the first dose, 36.2% of children aged 1-2 years, 52.5% of children aged 3-5 years, 56.7% of children aged 6-9 years, and 90.3% of adolescents aged 10-17 years generated protective antibodies. A second vaccination given 3 weeks later induced protective antibodies in 89.4% of all age groups. No severe adverse effects were found 6 weeks after vaccination.

Background: Despite recent advances in molecular epidemiology and pathogenecity analyses of extraintestinal Escherichia coli infections, detailed analyses identifying virulence factors of E. coli isolates from pediatric urosepsis patients have not been reported. This study was conducted to explore and differentiate bacterial virulence factors associated with urosepsis and 2 other severe parenchymal infections, acute pyelonephritis (APN) and acute lobar nephronia (ALN), in pediatric patients. Methods: Patients included in this study were those who fulfilled the diagnostic criteria of urosepsis, APN, and ALN, without underlying disease or structural anomalies, excluding those with vesicoureteral reflux. Patients with cystitis were included as controls. E. coli isolates from urine (cystitis, APN, and ALN) or blood (urosepsis) specimens were analyzed using polymerase chain reaction (PCR) for 25 virulence genes. Results: A total of 147 children (24 cystitis, 45 APN, 48 ALN, and 30 urosepsis) were enrolled in the study. Distinct syndrome-specific differences in the distribution for certain virulence genes, but conservation across syndromes for others, were found. In addition, urosepsis isolates presented higher aggregate virulence factor scores (P < 0.0001) compared with cystitis, APN, and ALN isolates. By contrast, cystitis isolates showed significantly lower aggregate virulence factor scores than all 3 invasive urinary bacterial infections; APN (P < 0.01), ALN (P < 0.01), and urosepsis (P < 0.0001). Conclusions: Our findings suggested that urosepsis isolates carry more virulence factors and are likely more urovirulent compared with cystitis, APN, and ALN isolates.

An association between hemophagocytic lymphohistiocytosis (HLH) and Kikuchi's disease is rarely seen in children. Here, we present the case of a male adolescent (age 16 years and 3 months) who suffered from spiking fever for more than 1 week, and multiple nodules over the neck and bilateral axilla for 2 months. A skin rash also developed over all four limbs, abdomen and face. Laboratory data and skin biopsy gave results compatible with a diagnosis of Kikuchi's disease. Hemophagocytosis in the bone marrow, hyper-triglyceridemia, elevated ferritin, and splenomegaly were also found, fulfilling the criteria for HLH. A recent primary Epstein-Barr virus infection was also diagnosed by serology. The patient ran a relatively benign course. Intravenous immunoglobulins, steroids or etoposide-containing regimens were not used, and his recovery was uneventful. A review of the literature showed that up to February 2009, 11 additional cases of Kikuchi's disease presenting simultaneously with, or mimicking, HLH had been reported. Complete resolution within several weeks, with no recurrence, was seen in all but one patient (a pregnant woman).

Background/Purpose Abdominal tuberculosis (TB) is a rare manifestation of childhood TB. Abdominal TB is characterized by long-lasting abdominal symptoms, which are usually confused with other conditions, and the diagnosis is usually delayed. Methods During a 5-year period, we identified 10 cases of abdominal TB in a tertiary care children's hospital. Data including demographic characteristics, presenting symptoms, history of Bacille Calmette-Guerin vaccination, lesion sites, laboratory data, image findings, diagnosis, tuberculin skin test, risk factors, treatment, and outcome were collected and analyzed. Results There were six female patients and four male patients, with a mean age of 14.7 years. One patient died due to the complication of disseminated TB with a pneumothorax. Household members with TB could be traced in six (60%) patients. The most common clinical presentations included fever (9/10), abdominal pain (8/10), and weight loss (8/9). The diagnosis of abdominal TB was suspected initially in only three patients; the others were not diagnosed until 7–36 days (mean=19 days) after hospitalization. The abnormal abdominal image findings, by either computed tomography or ultrasound, included lymphadenopathy (7/9), high-density ascites (6/9), thickening of the omentum or peritoneum (6/9), inflammatory mass (3/9), bowel wall thickening (1/9), and liver abscess (1/9). The chest radiography was abnormal in nine patients. Mycobacterium tuberculosis was isolated from ascites in two out of four patients, gastric aspirates in three, sputum in three, and intra-abdominal tissue specimens in two. Laparotomy was performed in three patients, laparoscopy in one, and colonoscopy in one. Conclusion In Taiwan, abdominal TB should be considered in patients with fever, abdominal pain, weight loss, and abnormal chest radiography. Characteristic computed tomography findings of abdominal TB and a history of exposure to TB contribute to the diagnosis.

Background/PurposeCoxsackievirus A2 (Cox A2) was the predominant serotype in the enterovirus outbreak in Taiwan, 2008. However, detailed clinical features of Cox A2 infection have not been reported. In this study, we compared Cox A2 with enterovirus 71 (EV71) in terms of clinical manifestation and epidemiology during the 2008 enterovirus outbreak in Taiwan.MethodsA total of 280 hospitalized patients (97 with culture-proven EV71 infection and 183 with culture-proven Cox A2 infection) in 2008 at the Chang Gung Children's Medical Center were enrolled in this study. Epidemiologic data, clinical manifestations, and outcomes for these patients were collected and compared.ResultsBoth Cox A2 and EV71 serotypes peaked in June and declined soon afterwards. Seventy-one percent of the patients were younger than 3 years of age. Both groups had the same male-to-female ratio of 1.6:1. Patients with EV71 infection had a significantly longer hospitalization period (4.1 vs. 3.0 days, p< 0.001). Fever, fever for more than 3 days with a temperature above 39°C, lethargy, poor activity, poor appetite and a myoclonic jerk were significantly associated with EV71 infection. Fever, or fever with a temperature above 39°C, febrile seizure, elevated white cell counts, and elevated serum C-reactive protein concentrations were significantly associated with Cox A2 infection. Most patients with EV71 infection presented with hand-foot-mouth disease (78.3%), while most Cox A2-infected patients presented with herpangina (83.6%). Central nervous system complications were found in 18.6% of EV71-infected children, but only in 1.1% of Cox A2-infected children. All the patients with Cox A2 infection showed total recovery. One patient with EV71 infection died from encephalitis with cardiopulmonary failure, and 6.2% of EV71-infected children had neurologic sequelae.ConclusionBoth Cox A2 and EV71 serotypes accounted for the enterovirus outbreak in Taiwanese children in 2008. Compared with those infected by EV71, the children with Cox A2 infection mostly presented with herpangina, had fewer central nervous system complications, and had better overall outcome.