Search

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

Inactivated influenza vaccination induces a hemagglutinin-specific antibody response to the strain used for immunization. Annual vaccination is strongly recommended for health care personnel. However, it is debatable if repeated vaccination would affect the antibody response to inactivated influenza vaccine through the time. We enrolled health care personnel who had repeated and first trivalent inactivated influenza vaccination in 2005–2008. Serological antibody responses were measured by hemagglutination-inhibition (HI) test. Subjects with repeated vaccination had higher pre-vaccination and lower post-vaccination HI titer than those with first vaccination, although serological responses between groups might vary with different antigen types and while the drifted strain was introduced in the vaccine. Higher fold rise in the HI titer was observed in the group with first than repeated vaccination and the fold increase in the HI titer was inversely correlated with pre-vaccination titer in 2007 and 2008. Nevertheless, no significant difference in the day 28 seroprotection rate was observed between groups with repeated and first vaccination in most circumstances. Further studies are needed to understand the long-term effect of repeated vaccination on the antibody response both at the serological and repertoire levels among health care personnel.

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

Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells.Open-label prospective randomized controlled trial.A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan.Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled.Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment.In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.

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.

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

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.

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.

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.

Few studies have assessed viral contamination in the rooms of hospital wards. This cross-sectional study evaluated the air and objects in patient-occupied rooms in pediatric wards for the presence of common respiratory viruses and Mycoplasma pneumoniae. Air samplers were placed at a short (60–80 cm) and long (320 cm) distance from the head of the beds of 58 pediatric patients, who were subsequently confirmed to be infected with enterovirus (n = 17), respiratory syncytial virus (RSV) (n = 13), influenza A virus (n = 13), adenovirus (n = 9), or M pneumoniae (n = 6). Swab samples were collected from the surfaces of 5 different types of objects in the patients’ rooms. All air and swab samples were analyzed via real-time quantitative polymerase chain reaction assay for the presence of the above pathogens. All pathogens except enterovirus were detected in the air, on the objects, or in both locations in the patients’ rooms. The detection rates of influenza A virus, adenovirus, and M pneumoniae for the long distance air sampling were 15%, 67%, and 17%, respectively. Both adenovirus and M pneumoniae were detected at very high rates, with high concentrations, on all sampled objects. The respiratory pathogens RSV, influenza A virus, adenovirus, and M pneumoniae were detected in the air and/or on the objects in the pediatric ward rooms. Appropriate infection control measures should be strictly implemented when caring for such patients.

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

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.

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

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.

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%

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.

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.

Among the 228 group B Streptococcus (GBS) isolates recovered in 2006 to 2008, higher resistance to erythromycin (58.3%) and clindamycin (57.9%) was found in isolates with certain resistance phenotypes. Serotype Ib isolates (24.6%) were the second most prevalent serotype, next to serotype V (29.4%), and showed the highest resistance rates to erythromycin (91.0%) and clindamycin (82.1%).

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.

As a member of orthomyxoviridae family, influenza viruses are enveloped viruses containing eight RNA segments. The main antigenic determinants of influenza A and B viruses are two surface glycoproteins, the hemagglutinin (H) and the neuraminidase (N). A genetic reassortment between influenza A viruses from different animal hosts may lead to an antigenic shift and thereby increase the risk of a potential pandemic. H1N1 and H3N2 subtypes of influenza A have been circulating all over the world as seasonal influenza since the last H3N2 pandemic in 1968.1 In April 2009, the Centers for Disease Control and Prevention of the United States identified two cases of human infection with the H1N1 novel influenza virus. The greatest initial burden of critical illness and deaths occurred in Mexico between March and June 2009. The virus is a triple-reassortant containing gene segments from swine influenza virus, human influenza virus, and avian influenza virus. Genes for hemagglutinin and neuraminidase come from swine influenza virus.2 On June 11th, 2009, the World Health Organization raised the level of influenza A (H1N1) pandemic alert from phase 5 to 6, as sustained communitylevel transmission of the virus is taking place in more than one region of the world. Recommendations for the Management of Children With H1N1 Novel Influenza Infection

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

Acute lobar nephronia (ALN) is a complicated acute renal infection that is part of the progression of the inflammatory process of acute pyelonephritis that can progress to renal abscess if left untreated. We examined the place of ALN in the spectrum of upper urinary tract infections.: The medical records of all patients diagnosed with ALN by computed tomography (CT) were reviewed retrospectively in terms of their demographic characteristics, clinical presentations, and laboratory findings. The patterns of the ALN lesions were checked on all contrast-enhanced CT films and the volume of the CT lesions (the extent of renal involvement) was estimated in every patient. Then, the correlation between the clinical presentation and CT lesions was examined.: Two distinct CT patterns of ALN lesions were observed in 127 patients: 94 simple ALN and 33 complicated ALN. Simple ALN appeared as striated or wedge-shaped, poorly defined regions of homogeneously decreased nephrographic density, whereas the lesions of complicated ALN showed heterogeneously decreased nephrographic density after contrast enhancement. The volume fraction of the CT lesions correlated well with the duration of fever before (P = 0.006) and after (P0.001) treatment in patients with simple ALN, while only the correlation between the fever duration after treatment and the volume fraction of the CT lesions (P0.001) was significant in patients with complicated ALN. Patients with complicated ALN were generally older (P = 0.004) and febrile longer after starting antibiotic treatment (P0.001). All treatment failures were in the complicated ALN group.: Children with ALN comprise 2 groups with different clinical presentations and treatment responses: simple ALN and complicated ALN. We suggest that simple ALN be regarded as a continuation of acute pyelonephritis and require 2 weeks of antibiotic treatment, while complicated ALN is a distinct more severe form requiring a 3-week or longer therapy regimen as the treatment of choice.

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.

The aim of this study was to evaluate immunity in HIV-uninfected children with bacille Calmette-Guerin-induced disease (BCG-ID) over an 8-year period, with particular emphasis on underlying diseases.Patient afflicted with BCG-ID proven by clinical courses, dermatologic features, pathology, specific polymerase chain reaction, and/or spoligotyping were enrolled between 2000 and 2007. Lymphocyte proliferation, polymorphonuclear function, interleukin (IL)-12/23-interferons (IFN)-gamma circuit, and Toll-like receptor 2-associated signaling were investigated.Of the 271,618 total live births who received the BCG vaccine, eight patients (seven males) with BCG-ID were enrolled during an 8-year period and presented as three disseminated, two distant, and three regional BCG-ID. Their age at onset ranged from 1 to 28 months. All had a vaccine-injection scar except for one with lower CD3 and natural killer cells, compatible with severe combined immunodeficiency (SCID) identified by IL-2 receptor common gamma chain (IL2RG) mutation (Arg226Lys). The other SCID patient with de novo IL2RG mutation (Trp74Gly) had more recurrent infections. The third patient with primary autoimmune neutropenia had disseminated BCG-ID extending to abdominal wall. The fourth patient with chronic mucocutaneous candidiasis had regional BCG-ID and impaired lymphocyte proliferation to Candida and BCG antigens. No defective evidence of polymorphonuclear functions, IL-12/23-IFN-gamma circuit, and Toll-like receptor 2-associated signaling was detected in the remaining four patients.Immunologic analysis in HIV-uninfected patients with BCG-ID reveals primary immunodeficiency diseases, especially in those with deficiencies in T-cell and neutrophil functions observed in our cohort, including primary autoimmune neutropenia and chronic mucocutaneous candidiasis.

SUMMARYOf 303 children hospitalized with acute non-bloody, non-mucoid diarrhoea, 69 (22·8%) had polymicrobial infection, including 52 (17·2%) multiple viral infection and 17 (5·6%) viral and bacterial co-infection. Rotavirus had the most important role in both categories; thus the control of rotavirus infection is crucial for maintaining children's health in Taiwan.

Background/Purpose An epidemic of severe acute respiratory syndrome (SARS) occurred in Taiwan from April to July 2003. A nosocomial outbreak of SARS occurred at Kaohsiung Chang Gung Memorial Hospital (CGMH) in May 2003. The purpose of our study was to survey the prevalence of the SARS coronavirus (CoV) in a community adjacent to Kaohsiung CGMH and collect demographic data, including basic information about health status, household, and possible risk factors for SARS-CoV infection. Methods We randomly recruited 1030 persons living in three precincts adjacent to Kaohsiung CGMH. For all subjects, we collected demographic data and measured the seroprevalence of the SARS-CoV with an enzyme-linked immunosorbent assay (ELISA) and an immunofluorescence assay (IFA). Results The ELISA was seropositive for 124 of 1030 participants (12%). The more sensitive and specific IFA confirmed SARS in only two cases (0.19%). Both confirmed cases were under 19 years of age and had no known SARS-related risk factors. Conclusion There was low post-epidemic seroprevalence of SARS-CoV in a community adjacent to a hospital which had a nosocomial SARS outbreak. The SARS outbreak in Taiwan was primarily limited to hospital settings.

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.