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Background/PurposeStreptococcus pneumoniae is the most common bacterial cause of community-acquired pneumonia in children. This study was designed to determine whether a newly designed urinary antigen test score correlated with severity of pneumococcal pneumonia in children.MethodsWe recruited 119 children hospitalized with pneumonia diagnosed by positive urinary pneumococcal antigen test at the National Cheng Kung University Hospital from 2002 through 2007. The urinary antigen reactivity score was determined by the rate of the reaction time and intensity of the pneumococcal antigen–antibody band. The children were stratified into three groups according to total score: group I, 8; group II, 5–7; and group III, 2–4. Disease severity was based on clinical presentation and radiological and laboratory findings.ResultsPatients in group I had significantly more respiratory distress (p = 0.01), oxygen desaturation (p = 0.04), febrile days (p = 0.03), pulmonary complications (p = 0.01), and bacteremia (p = 0.01), greater requirement for intensive care (p = 0.004), longer hospital stays (p

A total of 242 isolates were recovered from 76 patients with invasive diseases, 89 with scarlet fever, and 77 with pharyngitis. The most frequent emm types were types 12 (43.4%), 4 (18.2%), and 1 (16.9%). emm 12 reemerged in 2005 and peaked in 2007. emm 11 was recovered only from patients with invasive disease.

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

The investment on facilities for high-tech manufacturing requires a large amount of budget. One of the challenging issues for a firm is how to allocate finite budget to its factories and to fully utilize limited manufacturing resources. In this study, we develop a model to negotiate budget allocation among factories. During the negotiation, factories are modeled as intelligent agents and exchange a serie of messages with each others as bargaining over capital. A negotiation mechanism is designed in the study to mimic the attitude of a factory. Intrinsic and budget utility are used as performance indices to observe the behaviors of negotiation trajectories. The influence of the demand uncertainty are discussed under different settings of the negotiation-tactic combinations. Experimental outcomes have empirically justified that, the demand uncertainty significantly harms the social-welfare under the information asymmetric environment.

An outbreak of influenza A and influenza B appeared at the beginning and end of 2006 in southern Taiwan. We conducted this study to test whether laboratory findings could differentiate influenza A from influenza B infection.All children aged 16 years or less, who had nasal and/or throat swabs sent from inpatient or outpatient settings at National Cheng Kung University Hospital for the diagnosis of influenza infection from January 2005 to February 2007, were considered eligible subjects. Retrospective chart review of clinical and laboratory data was performed.274 patients were enrolled, 151 with influenza A and 123 with influenza B, of whom 127 (46.4%) received laboratory examinations. The peak month of influenza A and influenza B infections was January 2006 and January 2007, respectively. Children with influenza B infections were older than those with influenza A infections (p0.001). Influenza B-infected patients were more likely to have myalgia (p=0.004) than those with influenza A infections. Furthermore, children with influenza B infections tended to have lower leukocyte counts (6383 +/- 3970/mm3 vs 7639 +/- 3476/mm3, p=0.004), and higher serum creatine kinase level (p=0.002) than those with influenza A infections. The clinical outcomes were usually favorable.The clinical features of influenza B and influenza A infections are similar. However, decreased leukocytes and increased serum creatine kinase can be used as adjunctive criteria for diagnosis of influenza B infection before viral culture results are available.

Background Brainstem encephalitis (BE) is a serious neurological complication of enterovirus 71 (EV71) infection. The present study was designed to determine the characteristics of the chemokine response in the blood and cerebrospinal fluid (CSF) of patients with EV71-associated BE. Methods Thirty-one patients with BE were studied. They consisted of 12 with uncomplicated BE, 9 with autonomic nervous system (ANS) dysregulation, and 10 with pulmonary edema (PE); 13 healthy control subjects were also studied. Plasma and CSF concentrations of various chemokines were determined by a particle-based flow cytometry immunoassay. Results Plasma levels of interferon (IFN)-gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, monokine induced by IFN-gamma (MIG), and interleukin (IL)-8 were significantly higher in patients with PE than in those with uncomplicated BE. CSF levels of MIG were significantly higher in patients with PE than in those with uncomplicated BE and ANS dysregulation. The ratios of mean CSF to plasma levels for MCP-1 and IL-8 were highest in patients with uncomplicated BE and tended to fall with increasing severity of the disease. Conclusions Overexpression of the chemokine cascade in the central nervous system compartment appears to play an important role in the elicitation of the immune response to EV71. The chemokine CSF to plasma ratios suggest that IL-8, IP-10, MCP-1, and possibly MIG-but not RANTES-are synthesized in the brain in response to encephalitis.

Background In Taiwan, trivalent oral poliovirus vaccine (tOPV) is in the routine immunization schedule, but its association with illnesses had not been examined. Objectives To investigate clinical presentations and viral characteristics of patients with poliovirus isolates. Study design Clinical data, vaccination records and viral sequences were retrospectively analyzed for patients from whom polioviruses were isolated during 2000–2005. Results OPV-like strains were the only pathogen identified in 208 children who were diagnosed with lower respiratory tract infection (24.5%), acute gastroenteritis (16.8%) or upper respiratory tract infection (10.6%). Timing of poliovirus isolation relative to the tOPV vaccination was unusual in 59 patients, including 6 before any dose and 53 more than 10 weeks after the 3rd or later dose of tOPV. Sequence analyses of the VP1, 2C and 3C/D regions for 19 poliovirus isolates revealed that 4 had previously reported neurovirulence reversions, 1 had intertypic recombination, and 6 had both. No patient had neurological complications, but 3 died of myocarditis, including 2 with recombinant strains and 1 who never received OPV. Conclusion This study describes the isolation of OPV-like strains from patients with a variety of illnesses, raising concerns about their pathogenic potential in an area where tOPV is routinely administered. The detection of genetic variations among OPV-like strains warrants continuing surveillance for these variants in patients with severe illnesses besides neurological complications.

The aim of this study was to characterize the molecular epidemiology of invasive and non-invasive group A streptococcus (GAS) infections in children from 1997 through 2004 in southern Taiwan. A collection of 32 invasive and 150 non-invasive isolates were recruited for analysis. emm1 (34.4%) and emm12 (40.0%) predominated in the invasive and non-invasive isolates, respectively. The peak incidence of invasive GAS infection (IGASI) occurred between 2002 and 2003. emm4 and emm12 were the major types among clinical isolates before 2001, and was replaced by emm1 during 2002-2003. All emm1 isolates were clonal relatedness. The declined prevalence of erythromycin resistance occurred in the major shift of the endemic isolates to emm1 strains during 2002-2003 in the community.

Cytokines are intimately involved with the innate and adaptive immune response to bacterial infections. This study was designed to determine the expression of inflammatory cytokines in children by the severity of Streptococcus pyogenes (group A Streptococcus [GAS]) infections. The study population consisted of 16 invasive, 20 noninvasive, and 24 pharyngeal colonization, and 21 healthy controls. All children underwent the laboratory tests and cytokine measurement. GAS isolates were analyzed for emm gene typing. Patients with invasive GAS diseases had significantly higher interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, IL-8, IL-10, and IL-18 than those with noninvasive diseases, colonization, and healthy controls. There was no difference in tumor necrosis factor (TNF)-alpha, IL-12, and IL-2 levels among the groups. Elevated white blood cell counts and levels of C-reactive protein and C3 were detected only in patients with invasive diseases. emm1 and emm12 predominated in invasive disease and colonization. Children with invasive GAS infections exhibited significant up-regulation of plasma levels of IFN-gamma, IL-1beta, IL-6, IL-8, IL-10, and IL-18, and suppression of TNF-alpha and IL-12 during the acute phase of their illness. An exuberant cytokine response was associated with the severity of illness.

Group D non-typhoidal Salmonella infection is increasing in Taiwan. This study aimed to investigate the changing serotypes and antibiotic resistance of childhood group D Salmonella infection.From 1998 through 2004, children (16 years) infected with group D Salmonella were retrospectively reviewed. Demographic data, clinical and laboratory features, and risk factors of bacteremia were analyzed. Enrolled patients were classified as acute gastroenteritis with bacteremia (Group I) and acute gastroenteritis without bacteremia (Group II). The minimal inhibitory concentrations were determined by agar dilution method. Genotyping was performed by use of pulsed-field gel electrophoresis (PFGE).Eighty one children (Group I, n = 15; Group II, n = 66) were enrolled with a mean (+/- standard deviation) age of 3.1 +/- 2.6 years. Group I patients were younger and had a longer duration of fever prior to admission (or =5 days, 40% vs 9.2%; p=0.003) and total fever duration (8.3 vs 4.1 days, p0.001) than Group II. Salmonella enterica serotype Enteritidis (80%) was the most common serotype, followed by Salmonella Panama (7%). The antibiotic resistance rates of S. Enteritidis were: tetracycline (36.5%), trimethoprim-sulfamethoxazole (25.4%), ampicillin (14.3%), and chloramphenicol (12.7%). S. Panama was associated with a higher rate of bacteremia. All strains were susceptible to quinolone and third-generation cephalosporins. PFGE study showed a single genotype of S. Enteritidis and diverse genotypes of S. Panama circulating in the area.S. Enteritidis was the predominant serotype of group D Salmonella that caused pediatric infection in southern Taiwan during the study period from 1998 to 2004. S. Panama is associated with higher rates of bacteremia and antimicrobial resistance.

In this study, we sought to determine whether intratypic and intertypic cross-reactivity protected against enterovirus 71 (EV71) infection in a murine infection model. We demonstrate that active immunization of 1-day-old mice with avirulent EV71 strain or coxsackie A16 virus (CA16) by the oral route developed anti-EV71 antibodies with neutralizing activity (1:16 and 1:2, respectively). Splenocytes from both EV71- and CA16-immunized mice proliferated upon EV71 or CA16, but not coxsackie B3 virus (CB3), antigen stimulation. Immunized mice became more resistant to virulent EV71 strain challenge than nonimmunized mice. There was an increase in the percentage of activated splenic T cells and B cells in the immunized mice 2 days after EV71 challenge. The CA16 immune serum reacted with EV71 antigens in an enzyme-linked immunosorbent assay and neutralized EV71 but not CB3 or poliovirus at a titer of 1:4. Passive immunization with the CA16 immune serum reduced the clinical score, diminished the organ viral load, and increased the survival rate of mice upon EV71 challenge. CB3 neither shared in vitro cross-reactivity with EV71 nor provided in vivo protection after both active and passive immunization. These results illustrated that live vaccine is feasible for EV71 and that intertypic cross-reactivity of enteroviruses may provide a way to determine the prevalence of EV71.

Enterovirus 71 (EV71) infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. Several severe EV71 endemics have occurred in Asia-Pacific region, including Taiwan, and have become a serious threat to children's health. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells. Galectin-1 has been reported to participate in several virus infections, but is not addressed in EV71. In this study, we found that the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people. In EV71 infected cells, galectin-1 was found to be associated with the EV71 VP1 and VP3 via carbohydrate residues and subsequently released and bound to another cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenicity in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which could be restored following supplement of recombinant galectin-1. Taken together, our findings uncover a new role of galectin-1 in facilitating EV71 virus infection.

This study was designed to compare the change in complications of varicella infection in children requiring hospitalization before and after varicella vaccine introduction at a tertiary care hospital in southern Taiwan.Based on the results of a retrospective study conducted in the pre-vaccine era (1988-1998), a second study was carried out from 1998-2004 (post-vaccine era). In children admitted for varicella-related complications, demographic data, clinical features, microbiological findings, and outcomes were recorded and compared between the two eras.A decreased annual rate of hospitalization was observed between the two eras. Age-specific hospitalization rates significantly declined in the age group of 1-10 years after vaccine introduction. Secondary skin or soft tissue infections were the most common complications in both periods (pre-vaccine era, 44.1%; post-vaccine introduced era, 56.6%). In the post-vaccine era, 23 (52%) patients had positive bacterial isolates, including 19 Staphylococcus aureus (12 oxacillin-sensitive, 7 oxacillin-resistant) and 4 coagulase-negative staphylococci; a higher rate of pneumonitis and lower rate of central nervous system involvement were also observed. No differences were observed in other complications between the two eras. In the post-vaccine era, hematological diseases were the most common underlying conditions (17/18, 94%). The case-fatality rate in the post-vaccine era (1.3%) was similar to that in the pre-vaccine era (2.2%).A universal childhood varicella vaccination program would ultimately prevent the spread and potential complications of varicella. The result of this study may serve as baseline information as the national vaccination program begins.

The objectives of this study were to evaluate the protective effectiveness of various personal protective equipment and the respective exposure contributions from respiratory and skin exposures of N,N-dimethylformamide (DMF) with a self-comparison study design. Two high-, four intermediate- and four low-DMF exposure workers from a synthetic leather factory were monitored in airborne DMF concentrations and N-methylformamide (NMF) concentrations in urine across four consecutive days. The workers were designated to wear no personal protective equipment on the first day. The barrier cream, rubber gloves and rubber gloves plus respirator were used on the second, third and fourth days, respectively. Person-to-personal observation was performed in the field to record all high and low exposure tasks during work for each subject. Protective effectiveness index (PEI) was used to evaluate different glove effectiveness. We concluded that the direct skin contact to the strong skin penetrates like DMF could be a more significant exposure source than the respiratory exposure in the actual occupational environment. The provision of protective equipment from skin exposure could be more important than that from respiratory exposure. The application of barrier cream could be as effective as wearing impermeable rubber gloves in the prevention from the skin penetrate in the occupational settings.

In this study, the contribution of type I interferons (IFNs) to protection against infection with enterovirus 71 (EV71) was investigated using a murine model where the virus was administrated to neonatal Institute of Cancer Research (ICR) mice by either the intraperitoneal (i.p.) or the oral route. In i.p. inoculated mice, post-infection treatment of dexamethasone (5 mg kg−1 at 2 or 3 days after infection) exacerbated clinical symptoms and increased the tissue viral titre. In contrast, polyriboinosinic : polyribocytidylic acid [poly(I : C); 10 or 100 μg per mouse at 12 h before infection], a potent IFN inducer, improved the survival rate and decreased the tissue viral titres after EV71 challenge, which correlated with an increase in serum IFN-α concentration, the percentage of dendritic cells, their expression of major histocompatibility complex class II molecule and IFN-α in spleen. Treatment with a neutralizing antibody for type I IFNs (104 neutralizing units per mouse, 6 h before and 12 h after infection) resulted in frequent deaths and higher tissue viral load in infected mice compared with control mice. In contrast, an early administration of recombinant mouse IFN-αA (104 U per mouse for 3 days starting at 0, 1 or 3 days after infection) protected the mice against EV71 infection. In vitro analysis of virus-induced death in three human cell lines showed that human type I IFNs exerted a direct protective effect on EV71. It was concluded that type I IFNs play an important role in controlling EV71 infection and replication.

Patients of hematological malignancies with neutropenia form one of the most susceptible host groups for microbial infection. In this study, we concentrated on the pulmonary and cutaneous manifestations of invasive fungal infections in leukemic children, aiming to make early diagnosis and intervention. Clinical, laboratory, radiological, and histopathological findings concerning 13 leukemic children who had invasive fungal infection between 1997 and 2002 were retrospectively reviewed. Seventy-seven percent (10/13) of diagnoses were made by fungal cultures and/or by histopathological evidence from various specimens, four from cutaneous lesions and six from pulmonary tissues. Candidiasis was the most common infection (69%), followed by mucormycosis (15%), fusariosis (8%), and aspergillosis (8%). Three episodes of fungemia (23%) were identified. Lung (69%) and skin (69%) were the two most common sites of disseminated fungal infections. A premortem diagnosis was documented in 92% of the patients. Pathogens other than Candida albicans (85%) accounted for the great majority of cases. The case-fatality rate was 31% of disseminated fungal infections. A vigilant assessment of any suspicious lesion by physical and radiological examinations, including a biopsy of the lesions for microbiological and histopathological studies, may provide helpful for early diagnosis of disseminated fungal infections in leukemic children.

Several epidemics of enterovirus 71 (EV71) infections occurred in Taiwan since 1998.We performed the study to determine the changes in cytokine profiles associated with administration of intravenous immunoglobulin (IVIG) in patients with EV71-associated brainstem encephalitis complicated by autonomic nervous system (ANS) dysfunction and pulmonary edema.Plasma cytokine concentrations (IL-1beta, IL-6, IL-8, IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-10, and IL-13) were monitored on admission and within 12-24h after administration of IVIG in a cohort of children (n=22) with virologically confirmed EV71 infection, from March 2000 through April 2004.Plasma levels of IFN-gamma, IL-6, IL-8, IL-10, and IL-13 levels significantly decreased in patients with pulmonary edema after administration of IVIG, P0.05. Plasma levels of IL-6 and IL-8 were significantly decreased in patients with ANS dysregulation after administration of IVIG, P0.05. Administration of IVIG was not associated with significant changes in plasma concentration of IL-1beta, IL-2, IL-4, IL-5 IL-10, IL-13 and TNF-alpha in patients with ANS dysregulation.These findings suggest that IVIG might be considered to have a therapeutic role in EV71-associated brainstem encephalitis. A clinical trial is needed to support this hypothesis.

The study presented here aimed to elucidate the diagnostic value of bacterial stool cultures and viral antigen tests when performed based on the clinical characteristics of acute gastroenteritis in infants and young children. A total of 21 (11.2%) bacterial and 74 (39.6%) viral infections affecting 187 children under the age of 3 years was investigated. Blood (p0.001) and mucus (p=0.014) in the stool and a C-reactive protein (CRP) level ofor=50 mg/l (p=0.006) were more significantly associated with gastroenteritis of bacterial rather than viral origin. Vomiting (p0.001) was significantly associated with viral gastroenteritis. Among children with bloody stool, culture grew a Salmonella spp. in 35% and for vomiting children, stool antigen tests detected rotavirus in 60% of cases. In conclusion, etiologic tests to determine the cause of childhood gastroenteritis according to their characteristic clinical features or laboratory test results, or both, are of low diagnostic value.

Since the late 1990s, the epidemic of human immunodeficiency virus (HIV) infection in Taiwan has expanded dramatically. Pediatric HIV infection has also increased at an alarming pace. Nearly 40% of the HIV-infected children (10 years) contracted infection through mother-to-child transmission (MTCT). The aims of this study were to evaluate the effects of interventions to prevent MTCT of HIV infection, and to describe the clinical and immunologic characteristics of children born to HIV-seropositive mothers in southern Taiwan. From 1995 to 2003, an observational, longitudinal study of 8 children born to HIV-infected mothers was carried out at a tertiary care university hospital. The median age at enrollment was 0.4 years (range, 1 day-7.5 years), and the mean duration of follow-up was 2.7 years. Four mothers were immigrants from southeastern Asia. Due to antenatal diagnosis of maternal HIV infection, 3 children underwent interventions, including cesarean section, prophylactic use of zidovudine, and bottle-feeding in order to prevent vertical transmission. Five children were born without interventions because of delayed diagnosis of maternal HIV infection. During follow-up, 2 children were found to be HIV-infected and 6 were not infected. The rate of MTCT was lower among patients with interventions (0% vs 40%). In HIV-exposed/non-infected children, the clinical and immunologic assessments were normal during follow-up. Both HIV-infected children progressed to the stage of acquired immunodeficiency syndrome. Early identification of HIV-seropositive pregnant women, implementations to reduce vertical transmission, and introduction of antiretroviral therapy permit optimism in the prevention and treatment of pediatric HIV infection.

Hand, foot, and mouth disease and herpangina are the major clinical manifestations of enterovirus 71 (EV71) infections. Brain-stem encephalitis and pulmonary edema are severe complications that can lead to death. This study was designed to evaluate the potential therapeutic effect of milrinone, a phosphodiesterase (PDE) inhibitor, in the treatment of patients with EV71-induced pulmonary edema. We conducted a historically controlled trial of 24 children with severe EV71-induced pulmonary edema from April 1998–June 2003 in southern Taiwan. Patients were divided into groups treated before and after the introduction of milrinone therapy. Etiological diagnosis was established by viral cultures and confirmed by specific immunofluorescence and neutralization tests. All 24 patients were below 5 years of age. The mortality was lower in the milrinone-treated vs. nontreated group (36.4% vs. 92.3%, P = 0.005). Sympathetic tachycardia was decreased in patients treated with milrinone compared to controls (144 ± 17/min vs. 206 ± 26/min, P = 0.004). A marked decrease in IL-13 (77 ± 9 pg/ml vs. 162 ± 88 pg/ml, P = 0.001) was observed in milrinone-treated patients compared to controls. There was a significant reduction in white blood cell (10,838 ± 4,537/mm3 vs. 19,475 ± 7,798/mm3, P = 0.009) and platelet (257 ± 45 × 103/mm3 vs. 400 ± 87 × 103/mm3, P = 0.001) counts in milrinone-treated patients compared to controls. These results were associated with improvement in sympathetic regulation and decrease in IL-13 production. Milrinone therapy may provide a useful therapeutic approach for this highly lethal disorder. Pediatr Pulmonol. 2005; 39:219–223. © 2005 Wiley-Liss, Inc.

A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643 in mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643 in 1-day-old mice (50% lethal doses, 10 2 and 10 4 PFU/mouse, respectively). Strain MP4 (5 × 10 6 PFU/mouse), but not 4643, could orally infect 7-day-old mice, resulting in rear-limb paralysis followed by death 5 to 9 days after inoculation with the virus. Histopathologically, neuronal loss and apoptosis were evident in the spinal cords as well as the brain stems of the infected mice. The limb muscles displayed massive necrosis. There was early and transient virus replication in the intestines, whereas the spinal cord, brain, and muscle became the sites of viral replication during the late phase of the infection. Virus transmission occurred among infected and noninfected cagemates, as demonstrated by the occurrence of seroconversion and the presence of viable viruses in the stool samples of the latter. Protection against EV71 challenge was demonstrated following administration of hyperimmune serum 1 day after inoculation with the virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed four nucleotide changes on the 5′ untranslated region, three on the VP2 region, and eight on the 2C region, resulting in one and four amino acid substitutions in the VP2 and 2C proteins, respectively.

Group B Streptococcus (GBS) is widely recognized as a leading cause of neonatal sepsis and meningitis. Recently, GBS infections in older children have been increasingly noted. This retrospective study investigated the clinical features, distribution of serotypes, and antimicrobial susceptibility of GBS isolates in a tertiary care center in southern Taiwan over a 12-year period. GBS isolates recovered from various infected sites in 54 children treated from June 1991 through December 2002 were studied. These children were divided into those with disease onset of up to 3 months of age (group 1) and those with disease onset after 3 months of age (group 2). Patients in group 1 were subdivided into early-onset disease (EOD,7 days of age, 7/30) and late-onset disease (LOD,or =7 days to 3 months of age, 23/30). Sepsis (90% vs 8%; p0.01) and meningitis (40% vs 4.2%; p0.01) were observed more frequently in group 1, whereas urinary tract infection (UTI; 45.8% vs 6.7%; p0.01) and acute tonsillitis (33.3% vs 0%; p0.01) were noted more frequently in group 2. Underlying conditions were more common in group 2 than in group 1 (50% vs 10%; p0.01), especially in patients with UTI. The most frequently encountered serotype was serotype III (56%). Patients in group 1, especially those with LOD, and those who had meningitis or sepsis, were prone to develop serotype III infections (p0.05). All isolates were susceptible to penicillin G and cephalothin. About 50% of isolates were susceptible to erythromycin, azithromycin, and to clindamycin. In conclusion, GBS infection in children has different characteristics in different age groups. Serotype III is the most prevalent serotype in children. GBS isolates in southern Taiwan are still very susceptible to penicillin G.

Helicobacter pylori infection is primarily acquired in early childhood and its transmission routes are debated. The aims of this study were to determine the seroprevalence of anti-H. pylori immunoglobulin G (IgG) in Taiwanese and to investigate whether a common mode of transmission could be shared between H. pylori and hepatitis A virus (HAV).An enzyme-linked immunosorbent assay (ELISA) was used to investigate the prevalence of H. pylori among 924 healthy volunteers aged less than 40 years, and radioimmunoassay for HAV infection was conducted in 500 subjects from the same population. The kappa statistic was used to measure the difference in positivity for the 2 infections in a subgroup of 500 subjects who had their sera simultaneously tested for anti-H. pylori and anti-HAV antibodies.The seroprevalence of anti-H. pylori IgG was 16.7% in subjects aged16 years and 38.3% at agesor= 16 years. Most children (99%) under the age of 16 were seronegative for HAV. The prevalence of H. pylori infection increased rapidly with age, at 1%/year and 0.8%/year for children and adults, respectively. The rate of H. pylori infection was higher in male (21%) than in female (12%) children (p0.01; OR, 2.0; 95% confidence interval, 1.2 to 3.0). No significant difference in seroprevalence between genders was noted in subjects agedor= 16 years. The agreement in the trend of seropositivity between both infections in the age groups 1 to 10 years and 10 to 20 years was worse than chance (kappa = -0.56) and little better than chance (kappa = 0.01), respectively.Acquisition of H. pylori infection occurs at a young age, and male children are more likely to develop the infection. The main transmission route of HAV, the fecal-oral route, did not seem to be responsible for H. pylori transmission in this Taiwanese cohort.

This retrospective study investigated the causative pathogens, complications, and outcome of 58 children who were hospitalized for septic arthritis at a tertiary care hospital in southern Taiwan from July 1988 to December 2000. The mean age was 3 years (range, 12 days-16 years). The males/females ratio was 1.2:1. Ninety percent of the cases involved lower extremities (knee, hip, and ankle) with the hip being the most common site of infection (54%). Joint pain (81%) was the most common clinical presentation, followed by fever (74%), local warmness and swelling (72%), and limitation of motion (64%). Erythrocyte sedimentation rate was elevated (or = 20 mm/h) initially in 89% of the cases. The predominant causative organism was Staphylococcus aureus (43%, 25/58), 6 isolates of which were methicillin-resistant, followed by coagulase-negative Streptococcus (6), Streptococcus pneumoniae (3), Salmonella spp. (3), Haemophilus influenzae type b (2), and group B Streptococcus (2). The concomitant complications of septic arthritis were sepsis (9%, 5/58) and meningitis (2%, 1/58). Ten patients had sequelae, including limitation of motion (6), limping gait (2), limb-length discrepancy (1), and abnormalities of bone growth (1). This study found that S. aureus was the most common infecting microorganism in septic arthritis in children. Septic arthritis with concomitant osteomyelitis and infection due to methicillin-resistant S. aureus was associated with a significantly increased risk of sequelae (relative risk, 46.4, 95% CI, 2.9-748.8; relative risk, 16. 2, 95% CI, 1.3-204.9, respectively).

Taiwan experienced several epidemics of enterovirus 71 (EV71) infections, which were associated with brainstem encephalitis (BE) and pulmonary edema (PE). To elucidate the role of immune mechanisms in the pathogenesis of BE caused by EV71 and its fatal complication, PE, we analyzed the laboratory findings, cytokine, and immunophenotypes of 73 EV71-infected patients with BE. Patients were stratified by disease: PE (n=14), autonomic nervous system (ANS) dysregulation (n=25), and isolated BE (n=34). The mortality rate for PE was 64.3%. Leukocytosis and thrombocytosis were significantly more frequent among patients with PE. A significant elevation of plasma interleukin (IL)-10, IL-13, and interferon (IFN)-gamma levels observed in patients with PE. Patients with PE also had lower circulating CD4(+) T cells, CD8(+) T cells, and natural killer (NK) cells. An extensive peripheral and central nervous system inflammatory response with abnormal IL-10, IL-13, and IFN-gamma cytokine production and lymphocyte depletion appears to be responsible for the pathogenesis of EV71-associated PE.

Escherichia coli is the second most common bacterium isolated from the blood of neonates with sepsis. During a 12-year period from January 1988 through December 2000, E. coli sepsis or central nervous system infections were diagnosed in a total of 46 infants (M/F ratio, 3.6:1) in a tertiary care medical center. These infants were stratified into 3 groups according to age at disease onset. Group A include infants at birth to 7 days old; Group B, 7 days to 1 month old; and Group C, beyond 1 month old. Among them, 13 had sepsis, 24 had urosepsis, and 9 had meningitis or meningoencephalitis. All patients with central nervous system infections were younger than 40 days old. In the urosepsis group, 22 (91.7%) of 24 patients were younger than 6 months old with a male predominance (M/F ratio, 20:4), and 7 (29.2%) of 24 had urinary tract anomaly. Nine (68%) of 13 patients with sepsis had underlying disease. The most common clinical signs and symptoms were fever (89.1%), followed by tachycardia (71.7%), ill looking (50%), poor feeding (30.4%), and tachypnea (23.9%). The significant laboratory findings were elevated C-reactive protein (60.9%), and leukocytosis (56.5%) with left shifting (43.5%). Antimicrobial susceptibility test of the isolates showed a 67.7% resistant rate to ampicillin and a 35.5% resistant rate to chloramphenicol between 1994 and 2000. No significant increase in the resistance rate of the strains was noted compared with results from 2 studies conducted at different periods of time (1988-1993 and 1994-2000). Two infants with central nervous system infection died and 5 experienced major neurological sequelae. The clinical spectrum of invasive E. coli infections is age-related and associated with the underlying conditions. The prognosis was related to the development of central nervous system complications.

To identify the risk factors for Salmonella bacteremia in infants and children with Salmonella gastroenteritis, a retrospective study of a 10-year period was conducted to evaluate 456 infants and children with culture-proven nontyphoidal Salmonella infection. Salmonella typhimurium was the most common isolate found. Among the 257 patients with gastroenteritis who had a concomitant blood culture performed, 50 exhibited bacteremia. Statistically significant differences were noted between patients with gastroenteritis and bacteremia and those without bacteremia in duration of feveror = 5 days ( P0.001; OR, 5.6; 95% CI, 2.6 - 12.1) and infection with group D1 Salmonella ( P0.001; OR, 6.5; 95% CI, 2.5 - 16.9) after adjustment for multivariate analysis. Of the 320 Salmonella strains that were serotyped, Salmonella panama was shown to be strongly associated with bacteremia ( P0.001) in children with gastroenteritis. In summary, in children with nontyphoidal Salmonella gastroenteritis, prolonged fever lasting 5 days or more and infection with a specific Salmonella serotype were risk factors closely associated with development of bacteremia.

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

Background Since 1998, Taiwan has experienced several hand, foot, and mouth disease (HFMD) epidemics caused by enterovirus 71 (EV71). Two notable features of severe EV71 infection in young children are brainstem encephalitis (BE) and fatal pulmonary edema (PE). This study investigated the specific immunoregulatory characterizations of EV71 neurological complications according to the disease severity. Methods Patients younger than 18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the HFMD or BE group, and the autonomic nervous system (ANS) dysregulation or PE group. Laboratory findings, cytokine and cyclic adenosine monophosphate (cAMP) levels, immunophenotypes, and the regulatory T cell (Tregs) profiles of the EV71-infected patients were determined. Results Patients with ANS dysregulation or PE exhibited a significantly low frequency of CD4+ CD25+ Foxp3+ and CD4+ Foxp3+ T cells compared with patients with HFMD or BE. The expression frequency of CD4−CD8− was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+ Foxp3+ increased markedly after milrinone treatment, and was associated with a reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE, however, cAMP levels increased after milrinone treatment. Conclusions These findings provided new insight into the role of regulatory T cells. Furthermore, CD4+ CD25+ Foxp3+ and cAMP expression might be related to the progression of severe EV71 infection, and its responses to milrinone treatment.

Hepatitis A, the predominant reported etiologic form of viral hepatitis in Taiwan, continues to be a disease primarily of children and young adults. A seroepidemiologic study was performed to assess the seroprevalence of hepatitis A (HAV) antibodies in the southern Taiwan general population in 1998 and is compared with results of a similar study in 1992. A total of 948 subjects (477 male and 471 female) with ages ranging from 0.3 to 63 years were stratified into 14 age-specific groups. The presence of anti-HAV antibodies was detected using a commercially available radioimmunoassay. Fifteen percent of the subjects were positive for anti-HAV antibodies, which is lower than that in 1992 (P < 0.001). Seroprevalences were 14.1% for males and 22.6% for females (P = 0.006). The pattern of anti-HAV seroprevalence was distinguishable from that found in 1992; minimum seroconversion occurred at ages ranging from 1 to 30 years. Prevalence of seropositive subjects decreased markedly for the < 1, 13-15, 16-19, 20-24, 25-29, and 30-39 year age groups in comparing 1998 with 1992. The current study demonstrates a continuing decline in the prevalence of HAV among children, adolescents, and young adults. The findings can be ascribed to the improvement of socioeconomic status and modernization of environmental sanitation. As a consequence of this changing trend of endemicity and the resulting lack hepatitis A antibodies among the general population in Taiwan, the risk of sudden major outbreaks is increased because of increasing international travel and immigration, particularly during and after natural disasters. HAV vaccination will be important for the prevention and control of HAV outbreaks in the community.

Background: An outbreak of enterovirus infections occurred throughout Taiwan in 1998. The diseases were manifectated with hand, foot, and mouth disease (HFMD), some associated with meningitis, encephalitis, or acute flaccid paralysis (AFP). Objectives: This study is aimed to characterize and analyze the epidermologic and clinical features during the outbreak. Study design: The epidemiologic information was collected from the Ministry of Health on passive surveillance; clinical and virological investigations were carried out at National Cheng Kung University Medical Center. Results: Between April and December 1998, 405 children were hospitalized, and 78 patients died during this outbreak in Taiwan. There were 119 cases identified to be EV71 infection in Tainan and Chiayi areas; 105 cases by virus isolation and 14 by serological assay. The outbreak had a biphasic curve with peak in June and October, especially in the southern Taiwan. Seventy-two percent of patients were below 3 years of age. The spectrum of disease included HFMD in 54, HFMD with central nerve system (CNS) involvement in 37, herpangina in 12, aseptic meningitis in three, encephalitis/ meningoencephalitis in ten, acute flaccid paralysis in three. There was nine fatal cases complicated with neurogenic pulmonary edema. Myoclonus with sleep disturbance was the most important early sign of EV71 infection with CNS involvement. Conclusion: Our experience demonstrated that the EV71 isolated in Taiwan had strong dermatotropic as well as neurotropic tendencies. Early detecting CNS involvement and commencing aggressive therapy may reduce the mortality.

To assess trends in antimicrobial-resistant Salmonella infections from 1989 to 1996 in southern Taiwan, the minimum inhibitory concentrations (MICs) of 14 antibiotics or antibiotic combinations were determined by the agar dilution method for 297 clinical isolates of nontyphoidal Salmonella. The rates of resistance to ampicillin, chloramphenicol, and tetracycline were 65, 67, and 78%, respectively. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) increased from 25% in 1989-1992 to 35% in 1993-1996 (P=0.057). For new quinolones and extended-spectrum cephalosporins, no resistant strains were encountered. Multiple resistance to more than five antimicrobial drugs doubled from 10.6% in 1989-1992 to 19.7% in 1993-1996. Multiply resistant salmonellae were isolated more commonly from blood samples than from feces (30% vs. 14%, P

To analyze the high-resolution (i.e., 5.0- or 7.5-MHz) ultrasonographic (US) imaging characteristics of central nervous system (CNS) candidiasis and their histopathologic and magnetic resonance (MR) imaging correlates in very low-birth-weight (VLBW) premature neonates and infants with systemic candidiasis.The US images obtained in one VLBW neonate (age, 24 days; weight, 846 g) and four VLBW infants (age range, 36-161 days; weight range, 800-1, 360 g) with proved CNS candidiasis complicating systemic candidiasis and the clinical (n = 5), histopathologic (n = 3), and MR imaging (n = 2) correlates were retrospectively reviewed.The cranial US findings consisted of parenchymal abnormalities in four and ventricular lesions in three patients. The most common findings were multiple echogenic, rim-like microabscesses (four patients) scattered in the subcortical, periventricular, and basal ganglial areas. Confluent macroabscess formation, seen as echogenic mass-like lesions with hypoechoic centers in the periventricular regions and/or thalami, was noted on the US images obtained in two patients. The ventricles showed dilatation in two, increased ependymal echogenicity in three, the presence of intraventricular echogenic septa in two, and a lumpy choroid plexus or the presence of debris in two patients. US findings correlated well with MR imaging and autopsy findings. The histopathologic changes in the posterior fossa were well demonstrated on MR images but not demonstrated on 5.0- or 7.5-MHz US images.CNS candidiasis in VLBW neonates and infants has characteristic US features that may help in the early diagnosis of CNS involvement in systemic candidiasis.

Bilateral agenesis of the diaphragm is a rare, life-threatening malformation. Infants with this defect rarely survive to have surgical intervention. We report a 32-week premature female infant who was born to a 36-year-old mother via vaginal delivery. The pregnancy course was complicated by hypertension and polyhydramnios. Cytogenetic study showed a normal 46 XX female karyotype. She had cyanosis, respiratory distress and scaphoid abdomen at birth. A roentgenograph confirmed the diagnosis of diaphragmatic hernia. Surgery was performed at 21 h of age. Bilateral agenesis of diaphragm, herniation of abdominal organs and oesophagus and pulmonary hypoplasia were noted. Furthermore, stomach and spleen were adherent to the mediastinum and vertebrae. The patient developed hypotension and persistent hypoxaemia and expired at age of 26 h. Autopsy revealed bilateral agenesis of diaphragm, hypoplasia of lungs, and pancreas fibrosis with mild hypoplasia of islets of Langerhans.Bilateral agenesis of diaphragm associated with pancreas fibrosis is a rare entity, and its clinical significance needs further investigation.

Characteristics of the mutual coupling between rectangular microstrip antennas on a conducting ground plane of finite extent are experimentally investigated. The E- and H-plane mutual coupling coefficients of antennas on ground planes of various sizes are measured and analyzed. It is found that the finite extent of the ground plane has a greater effect on the E-plane coupling than on the H-plane coupling. © 1996 John Wiley & Sons, Inc.