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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.

In 500 children aged ≤10 years after 13-valent pneumococcal conjugate vaccine (PCV)13 immunisation in different schedules, serotypes 19A-specific and 19F-specific immunoglobulin G (IgG) were predicted to persist above 0.35 µg/mL for ≥10 years in all groups, likely due to PCV13-induced memory with natural boosting from residual diseases and colonisation. Generally, serotype-specific IgG could persist above 0.35 µg/mL longer (≥5 years) in the catch-up group than in the 2+1 and 3+1 immunisation groups. 14.5% of the carriage isolates belonged to PCV13 serotypes; statistical analysis revealed that a high serum IgG level (>10.96 µg/mL) will be required to eliminate the point-prevalence nasopharyngeal carriage of serotype 19A.

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 Because of several drawbacks, mouse brain-derived vaccine has been replaced by newer generation JE vaccines, including inactivated Vero cell-derived vaccine and live chimeric vaccine.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

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 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.

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

During recent 20 years, enterovirus A71 (EV-A71) has emerged as a major concern among pediatric infectious diseases, particularly in the Asia-Pacific region. The clinical manifestations of EV-A71 include uncomplicated hand, foot, and mouth disease, herpanina or febrile illness and central nervous system (CNS) involvement such as aseptic meningitis, myoclonic jerk, polio-like syndrome, encephalitis, encephalomyelitis and cardiopulmonary failure due to severe rhombencephalitis. In follow-up studies of patients with EV-A 71 CNS infection, some still have hypoventilation and need tracheostomy with ventilator support, some have dysphagia and need nasogastric tube or gastrostomy feeding, some have limb weakness/astrophy, cerebellar dysfunction, neurodevelopmental delay, lower cognition, or attention deficiency hyperactivity disorder. Long term sequelae may be related to greater severity of CNS involvement or neuron damage, hypoxia and younger age of onset.

Enterovirus A71 (EV-A71) is one of the causative pathogens of hand, foot, and mouth disease (HFMD), which may cause severe neurological and cardiopulmonary complications in children. In this review, we discuss the pathogenesis, clinical manifestations, management strategy, and clinical outcomes of cardiopulmonary failure (CPF) in patients with EV-A71 infection.The pathogenesis of CPF involves both catecholamine-related cardiotoxicity following brainstem encephalitis and vasodilatory shock due to cytokine storm. Sympathetic hyperactivity, including tachycardia and hypertension, are the early clinical manifestations of cardiopulmonary involvement, which may progress to pulmonary edema/hemorrhage and/or CPF. The management strategy comprises multidisciplinary supportive treatment, including fluid management, positive pressure ventilation support, and use of milrinone, vasopressors, and inotropes. Some patients may require extracorporeal membrane oxygenation. Major neurological sequelae are almost inevitable once a child develops life-threatening illness. Long-term care of these children is an important medico-social issue.

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.

North America experienced life-threatening outbreaks of enterovirus D68 (EV-D68) in 2014. We retrospectively detected EV-D68 from a child with Wilson's disease in 2008 in Taiwan. After comparing this EV-D68/Taiwan/2008 strain with EV-D68 genomes obtained from the public domain, it was classified as genome type 1-B; it is phylogenetically related to the predominant EV-D68 viruses that circulated in 2009 in Vietnam. It is necessary to strengthen EV-D68 detection globally, including in children with acute liver failure. Moreover, harmonization of genomic analysis of EV-D68 is desirable to understand global evolution of EV-D68. Keywords: Enterovirus D68, Genome study, Molecular epidemiology, Next-generation sequencing

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.

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

On the night of June 27th, 2015, a tragedy occurred while young people were celebrating the start of their summer break at the Formosa Fun Water Park in New Taipei City, Taiwan. At 8:32 PM, a blast caused by flammable cornstarch- based powder injured 499 people, including nine interna- tional tourists from five countries. Among the injured, half suffered burns over 40% of their body surface area (BSA), and 75% suffered from second or third degree burns to >20% BSA. The Taiwan emergency health care system encountered a very difficult challenge, and high fatality rates were ex- pected based on the seriousness of the injuries. The explosion was accidentally ignited from an over- heated spotlight on the stage in a dry swimming pool when colored powders were sprayed over the crowd. The un- precedented number of burn casualties caused panic in the Taiwanese public, and also brought into question the appropriateness of how ambulances were dispatched and the care received in the hospitals. On the night of June 27th, 2015, a tragedy occurred while young people were celebrating the start of their summer break at the Formosa Fun Water Park in New Taipei City, Taiwan. Immediately after the blast, the Ministry of Health and Welfare (MOHW) activated its two Regional Emergency Medical Operation Centers, notifying all emergency-designated hospitals to recall their medical personnel and prepare for mass burn casualties, and to report individual patient information and the number of patients entering each hospital. Facing the geographical limitations of the water park and the tremendous numbers of the injured, New Taipei and Taipei City dispatched >70 ambulances to the scene, along with ambulances from the cities of Keelung and Taoyuan, with the hospitals in these four cities volunteering to support the rescue. For better on-site response, the Ministry assisted in collaboration with the hospitals to set up on-site medical stations, and urged local health departments in these four cities to ensure that all burn units and intensive care units under their jurisdictions were well-prepared for the injured. With the intense cooperation and collaboration of fire departments and health departments, almost all of the 499 injured were sent to hospitals within an incredibly short period within 4 hours after the blast. The surge capacity of emergency rooms handling the injured was triggered in a very efficient way. It allowed these emergency rooms to obtain adequate staff, supplies, and equipment, as well as structures and systems to provide sufficient care to meet the immediate needs of patients following such a large-scale incident. Suffering from severe burns combined with inhalation pulmonary injuries, patients were unstable, and further intensive care was required. Patients were transferred to several hospitals with better burn-unit facilities to ensure the best medical care. Initially, the injured were treated in six hospitals in three cities in northern Taiwan. After they were stabilized, patients were distributed to 38 hospitals in seven cities by the following morning, with this distribution widened to 54 hospitals in 13 cities nationwide after 1 week. By the end of the 1st week, due to the less severely injured patients being discharged, patient distribution dropped to 46 hospitals in 13 cities... Language: en

Rotavirus infection has been the leading cause of gastroenteritis among children in Taiwan. Studies have shown that 40% of hospitalization for acute gastroenteritis can be prevented through the use of vaccines, including a live, attenuated monovalent rotavirus vaccine and a pentavalent, human–bovine reassortant rotavirus vaccine. In 2009, the World Health Organization suggested that rotavirus vaccine should be included in all national immunization programs. This review summarizes issues and recommendations discussed during an expert meeting in Taiwan. The recommendations included: (1) rotavirus vaccine should be offered to all healthy infants (including those without contraindications, such as immunodeficiency) at an appropriate age; (2) either monovalent or pentavalent vaccine can be administered concurrently with routine injected vaccines; (3) the administration of rotavirus vaccine must be administered at least 2 weeks prior to oral polio vaccination; (4) the first vaccine dose for infants should be administered between age 6 weeks and age 14 weeks 6 days and the course should be completed by age 8 months 0 day; (5) pentavalent vaccines can be administered at 2 months, 4 months, and 6 months while monovalent vaccines can be taken at 2 months and 4 months; (6) a combined use of monovalent and pentavalent vaccine is justified only when the previous dose is unavailable or unknown; and (7) rotavirus vaccines may be given to premature infants, human immunodeficiency virus infected infants and infants who have received or are going to receive blood products.

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 Shanghai fever, a community-acquired enteric illness associated with sepsis caused by Pseudomonas aeruginosa, was first described in 1918. The understanding of Shanghai fever is incomplete. Objective To delineate the clinical features and to examine the host and microbial factors associated with Shanghai fever. Methods We prospectively enrolled 27 consecutive previously healthy children with community-acquired P aeruginosa enteritis and sepsis between July 2003 and June 2012. An immunological investigation, including measurement of serum immunoglobulin levels and lymphocyte subpopulations, was performed. The clonal relationship of bacterial isolates was determined by multilocus sequence typing (MLST) and the virulence of isolates was measured using cellular and animal models. Results The median age of the patients was 7 months; 24 (89%) were aged

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.

Supplemental Digital Content is available in the text, The presence of anti-hepatitis B virus (HBV) core antibody (anti-HBc) is considered a sensitive lifetime marker of HBV infection. Here, we examined this dogma by investigating the prevalence of hepatitis B viremia in anti-HBc negative complete vaccines in Taiwan. A total of 795 participants (1.7–20.0 years old) had completed HBV vaccination in infancy and were anti-HBc negative. Serum samples were available for 460 individuals with isolated anti-HBV surface antibodies (anti-HBs) (HBsAg-negative and anti-HBc negative) and for 245 individuals who tested negative for all 3 markers (triple seronegative). All samples were submitted for polymerase chain reaction (PCR) targeting both the preS/S and X/pre-C gene regions. Of the 460 participants with isolated anti-HBs, 26 (5.65%) were positive for HBV by 2-target PCR. Of the 245 triple seronegative samples, 12 (4.90%) were positive for HBV DNA. In the former group, the prevalence of viremia was significantly higher in individuals aged 6 to 10 years than in all other ages combined (11.82% vs 3.7%, P = 0.001). The anti-HBs titers were significantly lower in participants 6 to 10 years old than in all other ages combined (72.06 vs 99.64 mIU/mL, P = 0.038). In total, 7 (0.99%) subjects had quantifiable HBV DNA levels (280–18,820 IU/mL). Sequence analysis of the S gene revealed vaccine escape like mutations. Hepatitis B viremia can occur in completely vaccinated individuals who are negative for anti-HBc.

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.

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.

Background/Purpose The immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae (H. Influenzae) protein D conjugate vaccine (PHiD-CV), co-administered with routine childhood vaccines, were assessed in Taiwanese infants. Methods In this open study, 230 healthy infants were primed with three doses of PHiD-CV (Synflorix) and diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa-HBV-IPV/Hib vaccine) at 1.5, 3 and 6 months of age and two doses of oral human rotavirus vaccine at 1.5 and 3 months. Pneumococcal immune responses were assessed 1 month post-dose three, by 22F-inhibition ELISA and opsonophagocytic activity (OPA) assay. Local and general solicited/unsolicited symptoms and serious adverse events (SAEs) were recorded. Results At least 95.4% of participants had an antibody concentration ≥0.2 μg/mL against each vaccine serotype. At least 96.1% of participants had an OPA titer ≥8 against each vaccine serotype except 6B (87.3%). All infants, but one, were seropositive for antibodies against nontypeable H. influenzae protein D. Immune responses to the co-administered vaccines were good and in line with previous reports. PHiD-CV was well tolerated, with low (≤6.3%) incidences of grade 3 solicited local symptoms. The frequencies of general symptoms were in line with other pneumococcal conjugate vaccine studies. There were no systematic increases in incidences of solicited general or local symptoms with successive doses. There were no reports of grade 3 fever (rectal temperature > 40 °C) or SAEs considered to be causally related to vaccination. Conclusion PHiD-CV co-administered with routine childhood vaccines within the first 6 months of life, was highly immunogenic, and well tolerated in Taiwanese infants.

Despite the success of a universal vaccination program against hepatitis B virus (HBV) in Taiwan, a small but substantial proportion of individuals remain infected by mutant viruses that escape the vaccine. We investigated the seroepidemiology and genotypic characteristic of HBV for long periods after neonatal vaccination.We measured hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and antibody to hepatitis B surface antigen (anti-HBs) in 1214 serum samples collected throughout Taiwan from individuals 0.6-87.8 years old in 2007. HBV DNA was detected using polymerase chain reaction and sequence analysis in vaccine recipients who tested positive for anti-HBc and/or HBsAg.The overall seroprevalence of HBsAg and anti-HBc was significantly lower among individuals born after the initiation of the nationwide vaccination program (P.001). However, we observed increasing seroprevalence of anti-HBc and isolated anti-HBs when subjects were grouped by age: at 10-14, 14-18, to 18-21 years of age, values were 0.4%, 1.9%, and 8.1% (P = .0135) and 43.7%, 55.4%, and 59.6% (P = .0093), respectively (χ(2) test for trend). A large increase was observed in the percentage of patients who tested positive for HBV DNA at 18-21 years of age (3.0% vs 0.2% [P = .002] for all eligible subjects and 5.7% vs 0.3% [P.001] for subjects vaccinated with ≥3 doses). Five of 8 completely vaccinated individuals who were seropositive for HBV DNA carried variants with mutations in the S gene.Universal vaccination effectively controls HBV infection in children and adolescents. However, after adolescence, there is a significant increase in the seroprevalence of anti-HBs, anti-HBc, and HBV DNA, indicating that new preventative strategies are needed for adults.

Purpose Long-term immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine when administered to adolescent girls was evaluated. Methods This open-label, follow-up study (NCT00316706) was conducted in 31 centers in Taiwan, Germany, Honduras, Panama, and Colombia. In the initial study (NCT00196924), 1,035 girls aged 10–14 years received the HPV-16/18 AS04-adjuvanted vaccine at 0, 1, and 6 months. Here, geometric mean titers (GMTs) of antibodies against HPV-16, HPV-18, and monophosphoryl lipid A (MPL), a component of the AS04 Adjuvant System, were reported up to month 48. Results In the according-to-protocol immunogenicity cohort (N = 563), GMTs at month 48 in initially seronegative participants were 2,374.9 (95% confidence interval: 2,205.7–2,557.0) EL.U/mL for anti-HPV-16 and 864.8 (796.9–938.4) EL.U/mL for anti-HPV-18, that is, six- and threefold higher than the plateau level in a reference study demonstrating vaccine efficacy in young women (age, 15–25 years). All participants remained seropositive for anti-HPV-16 and anti-HPV-18 at month 48. Most participants (81.8%) were seropositive for anti-MPL antibodies before vaccination. Anti-MPL antibody titers in initially seropositive participants increased initially, and then declined. Most initially seronegative participants for anti-MPL seroconverted; 69.6% remained seropositive at month 48, with anti-MPL antibody titers similar to the natural background level. The vaccine was generally well tolerated. No serious adverse events were considered related to vaccination. Conclusions In adolescent girls, the HPV-16/18 AS04-adjuvanted vaccine produces anti-HPV-16 and anti-HPV-18 antibody titers that are maintained for up to 4 years at higher levels than those in young women in whom vaccine efficacy against cervical lesions was demonstrated.

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.

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%

Methicillin-resistant Staphylococcus aureus (MRSA) has been identified as a major cause of community-associated (CA) S. aureus infections in the past decade. The main reservoir in the community for MRSA and the factors contributing to its worldwide spread remain poorly defined. Between July 2005 and June 2008, a total of 6,057 healthy children 2 to 60 months of age were screened for carriage of S. aureus and Streptococcus pneumoniae in Taiwan. The prevalence and epidemiological factors influencing MRSA carriage were determined. MRSA strains were tested for antimicrobial susceptibility and underwent molecular characterization. The overall prevalences of MRSA and S. aureus carriage were 7.8% and 23.2%, respectively. A majority (88%) of MRSA isolates belonged to a common Asian-Pacific CA-MRSA lineage, multilocus sequence type 59, and were resistant to multiple non-beta-lactam antibiotics. The carriage rate of MRSA was higher among subjects 2 to 6 months old ( P < 0.0001), residing in northern Taiwan ( P = 0.0003), and enrolled later in the study ( P < 0.0001). MRSA colonization was associated with the number of children in the family (adjusted odds ratio [aOR], 1.114; 95% confidence interval [CI], 1.002 to 1.240; P = 0.0463) and day care attendance (aOR, 1.530; 95% CI, 1.201 to 1.949; P = 0.0006). Breast feeding ( P < 0.0001) and colonization with S. pneumoniae ( P = 0.0170) were protective against MRSA colonization. We concluded that epidemic CA-MRSA strains increasingly colonized Taiwanese children between 2005 and 2008. The carriage rate varied significantly across different demographical features. Crowding was an independent environmental risk factor that might accelerate CA-MRSA transmission in the community.

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.

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.

Between 1991-2006, nine patients below age 18 years, with a microbiologic documentation of Cryptococcus neoformans infection and no evidence of human immunodeficiency virus infection, were identified and treated at Chang Gung Children's Hospital. All exhibited central nervous system involvement. Seven patients were female (age range, 9-16 years; mean age, 13.7 years). Five patients (56%) manifested underlying diseases and were receiving either steroid or immunosuppressant treatment at time of disease onset. Eight patients presented with meningitis. Headache, vomiting, and focal neurologic signs were the most common presentations. Protein and sugar levels in cerebrospinal fluid were within normal range in seven cases, whereas India ink smear and cryptococcal antigen testing were positive in 87% (7/8) and 78% (7/9) of patients, respectively. With prompt antifungal therapy, all survived, but one presented the sequel of blindness. Cryptococcosis is uncommon in the nonhuman immunodeficiency virus-infected pediatric population. Clinicians should take into account a diagnosis of central nervous system cryptococcosis when children present with prolonged headache, vomiting, and focal neurologic signs. Indian ink stain and cryptococcal antigen testing of cerebrospinal fluid should be performed.

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.

BackgroundVentilator-associated pneumonia (VAP) is a common clinical problem. Previous studies involving adult patient cohorts have assessed various risk factors associated with VAP, including ventilator circuit changes. The objective of this study was to examine the incidence of and risk factors associated with VAP, particularly 3-day versus 7-day ventilator circuit changes, in a pediatric intensive care unit (PICU).MethodsThis was a cohort observational study. Patients hospitalized in the PICU at Chang Gung Children's Hospital between November 2003 and September 2004 were enrolled. Investigators and critical-care specialists evaluated baseline characteristics, incidence of VAP, and related variables from PICU admission until discharge or death.ResultsOf 397 patients initially enrolled, 96 (aged 11–60 months) were available for statistical analysis and were assigned into two groups according to timing of ventilator circuit change: 3-day (n = 46) and 7-day circuit change (n = 50). No statistically significant differences were observed for VAP incidence (13% vs. 16%, p = 0.68) or hospital mortality (22% vs. 36%, p = 0.14) for 3-day versus 7-day circuit change. Incidence of VAP per 1000 ventilation days was 10.75 and 8.41 for 3-day and 7-day circuit change, respectively. Univariate analysis indicated statistical significance for the duration of mechanical ventilation (10.17 ± 16.63 days vs. 18.20 ± 14.99 days, p< 0.001), length of stay in PICU (22.30 ± 20.48 days vs. 37.22 ± 36.79 days, p= 0.0069) and presence of enteral nutrition [7 (15.22%) vs. 23 (46.0%), p = 0.0012].ConclusionWeekly circuit change does not contribute to increased rates of VAP in pediatric patients. Long-term studies evaluating risk factors in larger pediatric patient populations are warranted for further conclusive recommendations.

Human metapneumovirus (hMPV) causes both upper and lower respiratory tract infection worldwide. Because little is known about the estimated level of exposure to hMPV in Taiwan, data for 1999 are presented. One thousand one hundred twenty sera from otherwise healthy community-based subjects aged 1 month to 99 years were tested in an enzyme-linked immunosorbent assay; the proportion of seropositive individuals was 68.1%. Moreover, 53.2% of preschool children were seronegative, whereas 88.3% of school-aged individuals and 93.7% of adults had antibodies to hMPV. In summary, the present study provides an earlier evidence of a high rate of exposure to hMPV characterized the seroprevalence among Taiwanese individuals in 1999. In addition, our findings suggest that preschool children in particular would benefit from vaccination against hMPV.

Pott’s puffy tumor is characterized by subperiosteal abscess associated with osteomyelitis of frontal bone. Reports are limited for this rare entity in the antibiotics era but increase during past decade. We had clinical analysis of a series with six consecutive pediatric patients of Pott’s puffy tumor during 20 years in a tertiary medical center via retrospective chart review. One case was described in detail. Male-to-female ratio was 5:1. The mean age at the time of diagnosis was 13 years–3 months. The risk factors were acute sinusitis in two (33%), chronic sinusitis in two (33%), recent head trauma in two (33%), and acupuncture therapy on skull in one (17%). The commonest presenting symptoms were fever, headache, forehead tenderness, vomiting, and fatigue/malaise (100%). Pott’s puffy tumor was diagnosed on average the seventh day after fever, and half had intracranial involvement at diagnosis. All had intracranial infections, and most of them had subdural empyema. The most often involved sinus was frontal sinus (100%). The frontal lobe was the most common site of intracranial infection (100%), two thirds of which are polymicrobial from two or more sites. The initial operation was performed on average on the 5.8th days after diagnosis. Half of the patients underwent reoperation. The mortality rate was 17% (one of six). The symptoms of Pott’s puffy tumor are inconspicuous even though early intracranial involvement often occurred. The importance of early diagnosis and aggravated and prompt treatment with prolonged antibiotic therapy is emphasized for better outcome.

BACKGROUND Norovirus and rotavirus cause outbreaks of diarrheal disease worldwide. This prospective observational study was undertaken to investigate the clinical characteristics and complications, with a focus on convulsive disorders, of gastroenteritis caused by norovirus and rotavirus in hospitalized pediatric patients in northern Taiwan. METHODS Children hospitalized with acute gastroenteritis in Chang Gung Children's Hospital from August 2004 through January 2007 were enrolled in the study. Rotavirus and norovirus were detected by reverse-transcriptase polymerase chain reaction with fecal specimens and were genotyped by sequence analysis. The symptoms and complications, in particular convulsions, of acute gastroenteritis caused by rotavirus and norovirus were reviewed and compared. The occurrence of convulsions associated with norovirus infection was specifically analyzed and discussed. The neurological outcomes for all norovirus-infected patients with or without convulsions were followed up for 1 year. Results. Among the 353 patients with acute viral gastroenteritis without coinfection, rotavirus and norovirus isolates were detected in 101 patients (28.6%) and 64 patients (18.1%), respectively. We compared the symptoms between the 2 groups and found that rotavirus caused a higher frequency and longer duration of vomiting and a higher body temperature than did norovirus. Norovirus infection, on the other hand, caused significantly longer hospital stays (mean duration of stay [interquartile range], 6 [5-8] days vs. 5 [4-7] days; P

Background/Purpose Rotavirus infection is the most common etiology of acute gastroenteritis in young children worldwide. The first rotavirus vaccine was licensed by the United States Food and Drug Administration in 1998 but was suspended soon after in 1999 because of the possibility of induced intussusception. This study evaluated the safety and immunogenicity of a newly developed pentavalent rotavirus vaccine in Taiwanese children. Methods This was a phase III global trial designed to evaluate the safety and immunogenicity of an oral, live pentavalent rotavirus vaccine (RotaTeq™). Taiwan was the only site in Asia enrolled in this trial. Normal healthy infants aged 6–12 weeks were enrolled, and each of the subjects received either three oral doses of the vaccine or placebo solution. The safety of the vaccine, particularly the risk of intussusception, and immunogenicity were studied. Results A total of 189 infants were enrolled. No increased risk of intussusception or other adverse reactions were noted following the vaccination. RotaTeq™ was immunogenic among subjects enrolled in Taiwan. At least a three-fold rise in serum antirotavirus IgA antibody was found among 93% of the vaccine group. The immunogenicity of RotaTeq™ in Taiwan was comparable to that in other areas. Conclusion The pentavalent human-bovine vaccine, RotaTeq™, was safe, generally well-tolerated, and immunogenic among Taiwanese infants.

Modulation of the intestinal immune response early in life by administration of probiotic bacteria may be an effective strategy for preventing or attenuating infectious diarrhea. We preinoculated the mice early in life with the probiotic bacteria Lactobacillus acidophilus NCFM (La) at age 2 wk. Dendritic cells (DCs) were collected and purified from mesenteric lymph nodes (MLN) and spleens of the BalbC/ByJ mice. DC isolation and adoptive transfer was used to examine the function of probiotics. We demonstrated that when mice were adoptively transferred with La-primed DCs (t-LaDC) instead of oral consumption with La, there was a similar effect on fecal bacteria counts, IgA levels, and colonic histopathology, as well as cytokine levels in MLN when there was intestinal bacterial infection. The above findings suggest that DCs play a key role in probiotics attenuating Citrobacter rodentium (Cr) colitis. Moreover, the location of La-primed DC hints that there is interaction of DCs and T cells in the digestive system of the host. Up-regulated expression of a surface marker on DCs indicated that inoculation with probiotics will stimulate the function of DCs, thereby further increasing immune response triggered by DC.

IL-12/23-interferon-gamma circuit enhances reactive oxygen species (ROS) synthesis in macrophage to attack intracellular pathogens such as mycobacteria and salmonella. Defective ROS in patients with chronic granulomatous disease (CGD) have increased susceptibility to these pathogens. However, patients with defective IL-12/23-interferon-gamma circuit rather than CGD are not recognized in Taiwan, endemic for tuberculosis and salmonella.The purpose of this study was to identify Taiwanese patients with defective IL-12/23-IFN-gamma circuit.In a long-term molecular study of primary immunodeficiency diseases (PIDD), the tentative CGD patients presenting with Bacille Calmette-Guerin (BCG)-induced infection, refractory atypical mycobacterial cutaneous granuloma and osteomyelitis, recurrent salmonella sepsis, and pneumatocele were studied for the IL-12/23-IFN-gamma circuit. ROS was first measured to exclude CGD. Candidate genes of IL12RB1, IFNRG1, IL12p40, IFNRG2, signal transducer and activator of transcription-1, and NF-kappaB essential modulator and their encoding protein expressions were analyzed.Of the 175 Taiwanese PIDD patients during a 28-year period, three patients from two unrelated families were identified with the hotspot INFRG1 deletion mutation (818del4) and had CGD features, presenting as cutaneous granuloma, and multiple osteomyelitis infected by non-tuberculosis mycobacteria, Mycobacteria avium complex and Mycobacterium scrofulaceum. Another with mis-sense IL12RB1 mutation (Arg211Pro) was noted as recurrent Salmonella enteritidis D sepsis and pneumatocele.Patients with defective IL-12/23-IFN-gamma circuit may resemble or overlap CGD manifestations of refractory cutaneous atypical mycobacterial granuloma and salmonella pneumatocele.

BACKGROUND. No study has investigated the association between enterovirus 71 central nervous system infection and symptoms related to attention-deficit/hyperactivity disorder. In this study we evaluated attention-deficit/hyperactivity disorder–related symptoms and internalizing problems as long-term sequelae resulting from enterovirus 71 central nervous system infection in children.METHODS. We enrolled 86 children 4 to 16 years old with virus-culture–confirmed enterovirus 71 infection and central nervous system involvement diagnosed 3 to 7 years before the study and 172 control subjects, matched for age, gender, and parents’ education levels. Their mothers and teachers were asked to report on possible attention-deficit/hyperactivity disorder–related symptoms, and their mothers were asked to report on possible internalizing problems. All of the children previously infected with enterovirus 71 received intelligence tests.RESULTS. Forty-two (49%) of the children previously infected with enterovirus 71 had had viral meningitis; 35 (41%) had severe central nervous system involvement, such as encephalitis, poliomyelitis-like syndrome, or encephalomyelitis; and 9 (10%) had cardiopulmonary failure and central nervous system involvement. The children previously infected with enterovirus 71 had higher scores than matched control subjects on teacher- and mother-rated scales of inattention, hyperactivity-impulsivity, oppositional symptoms, and attention-deficit/hyperactivity disorder index. The rate of elevated attention-deficit/hyperactivity disorder–related symptoms among children with enterovirus 71 central nervous system infection was 20%, whereas that rate among matched control subjects was only 3%. They also had more internalizing problems. Their verbal and performance IQs, as well as verbal comprehension indices, were significantly inversely correlated with symptoms of inattention, hyperactivity-impulsivity, and attention-deficit/hyperactivity disorder index scores.CONCLUSIONS. Enterovirus 71 central nervous system infection may affect long-term regulation of attention and emotion and cause hyperactivity-impulsivity in children.

We report unusual cases of myocarditis caused by enterovirus 71 (EV71) and a declining trend in the incidence of EV71 in Taiwan since 2005. Furthermore, phylogenetic analysis of the 5' untranslated region, VP4, and VP1 genes of EV71 isolates in 2004-2005 revealed a divergent phylogeny from the previous Taiwanese isolates. No obvious phylogenetically distinct clones or clusters were found related to varying degrees of disease severity or clinical manifestations.

From July 2005 to October 2006, a total of 3,046 children, of ages between 2 months and 5 years, presented for a well-child health care visit to one of three medical centers, which are located in the northern, central, and southern parts of Taiwan, and were surveyed for nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA). The overall prevalences of S. aureus and MRSA nasal carriage among the children were 23% and 7.3%, respectively (18% and 4.8% in the central region, 25% and 6.7% in the southern region, and 27% and 9.5% in the northern region). Of the 212 MRSA isolates (96%) available for analysis, a total of 10 pulsed-field gel electrophoresis (PFGE) patterns with two major patterns (C [61%] and D [28%]) were identified. One hundred forty-nine isolates (70%) contained type IV staphylococcal cassette chromosome mec (SCC mec ) DNA, and 55 isolates (26%) contained SCC mec V T . The presence of Panton-Valentine Leukocidin (PVL) genes was detected in 60 isolates (28%). Most MRSA isolates belonged to one of two major clones, characterized as sequence type 59 (ST59)/PFGE C/SCC mec IV/absence of PVL genes (59%) and ST59/PFGE D/SCC mec V T /presence of PVL genes (25%). We concluded that between 2005 and 2006, 7.3% of healthy Taiwanese children were colonized by MRSA in nares. MRSA harbored in healthy children indicates an accelerated spread in the community.