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A vapor-phase process, involving the sublimation of an ice substrate/template and the vapor deposition of a maleimide-functionalized poly-p-xylylene, has been reported to synthesize an advanced porous material, with readily clickable chemical interface properties, to perform a Michael-type addition of a maleimide functionality for conjugation with a thiol group. In contrast to the conventional chemical vapor deposition of poly-p-xylylenes on a solid surface that forms thin film coatings, the process reported herein additionally results in deposition on a dynamic and sublimating ice surface (template), rendering the construction of a three-dimensional, porous, maleimide-functionalized poly-p-xylylene. The process seamlessly exploits the refined chemical vapor deposition polymerization from maleimide-substituted [2,2]paracyclophane and ensures the preservation and transformation of the maleimide functionality to the final porous poly-p-xylylene products. The functionalization and production of a porous maleimide-functionalized poly-p-xylylene were completed in a single step, thus avoiding complicated steps or post-functionalization procedures that are commonly seen in conventional approaches to produce functional materials. More importantly, the equipped maleimide functionality provides a rapid and efficient route for click conjugation toward thiol-terminated molecules, and the reaction can be performed under mild conditions at room temperature in a water solution without the need for a catalyst, an initiator, or other energy sources. The introduced vapor-based process enables a straightforward synthesis approach to produce not only a pore-forming structure of a three-dimensional material, but also an in situ-derived maleimide functional group, to conduct a covalent click reaction with thiol-terminal molecules, which are abundant in biological environments. These advanced materials are expected to have a wide variety of new applications.

Conventional porous materials are mostly synthesized in solution-based methods involving solvents and initiators, and the functionalization of these porous materials usually requires additional and complex steps. In the current study, a methyl propiolate-functionalized porous poly-p-xylylene material was fabricated based on a unique vapor sublimation and deposition process. The process used a water solution and ice as the template with a customizable shape and dimensions, and the conventional chemical vapor deposition (CVD) polymerization of poly-p-xylylene on such an ice template formed a three-dimensional, porous poly-p-xylylene material with interconnected porous structures. More importantly, the functionality of methyl propiolate was well preserved by using methyl propiolate-substituted [2,2]-paracyclophane during the vapor deposition polymerization process and was installed in one step on the final porous poly-p-xylylene products. This functionality exhibited an intact structure and reactivity during the proposed vapor sublimation and deposition process and was proven to have no decomposition or side products after further characterization and conjugation experiments. The electron-withdrawing methyl propiolate group readily provided efficient alkynes as click azide-terminated molecules under copper-free and mild conditions at room temperature and in environmentally friendly solvents, such as water. The resulting methyl propiolate-functionalized porous poly-p-xylylene exhibited interface properties with clickable specific covalent attachment toward azide-terminated target molecules, which are widely available for drugs and biomolecules. The fabricated functional porous materials represent an advanced material featuring porous structures, a straightforward synthetic approach, and precise and controlled interface click chemistry, rendering long-term stability and efficacy to conjugate target functionalities that are expected to attract a variety of new applications.

This paper examines the theoretical literature and conducts empirical analysis on the mechanisms of corporate governance. We focus on directors’ role in ameliorating various types of agency problems (e.g., corporate misconduct) arising from conflicts of interests between stakeholders and managers to the firm. In a sample of 45 public listed construction companies in Taiwan between 2005 and 2014, the result indicates that illegal corporate behavior is more likely to occur in firms with large boards while board independence isn’t significant for misconduct constraining. The finding also shows why board’s monitoring function is important and how firms rein in misconduct by altering board size and composition.

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

Background Empiric antibiotics are frequently given for children with acute exudative tonsillitis. A few studies have investigated the causative agent of acute "exudative" tonsillitis in children to evaluate the necessity of antibiotic therapy. This study tried to explore the common causative agent of acute exudative tonsillitis among children. Methods From April 2009 to March 2010, throat swabs were obtained and cultured for viruses and bacteria from children who visited the pediatric emergency rooms of two medical centers in central Taiwan with acute exudative tonsillitis. Demographic data and microbiological results were analyzed. Results A total of 294 children with acute exudative tonsillitis were enrolled during the 1-year prospective study, and 173 (58.8%) of them were younger than 7 years. Group A streptococci were isolated from only three (1.0%) children, and they were all older than 6 years. A total of 143 viruses were isolated from 140 (47.6%) children. Adenovirus (18.7%) and enterovirus (16.3%) were the most common viral etiologies, followed by influenza virus (5.4%), parainfluenza virus (5.1%), herpes simplex virus Type 1 (2.7%), and respiratory syncytial virus (0.3%). Group A streptococcus only contributed to a minimal portion of acute exudative tonsillitis. Conclusion Routine or immediate antibiotic therapy for acute exudative tonsillitis in children is not necessary.

This study was designed to assess the clinical effect of a home-based telephone intervention in Chinese heart failure patients. A total of 550 Chinese heart failure patients were enrolled into either (i) a group that received the usual standard of care (UC group); or (ii) a group that received a home-based heart failure centre management programme using nursing specialist-led telephone consultations (HFC group). The impact of the home-based intervention on admission rate, admission length and medical costs over 6 months was measured. Although the mean left ventricular ejection fraction in HFC patients was 29.3% compared with 34.8% in UC patients, the home-based intervention resulted in a significantly lower all-cause admission rate per person (HFC 0.60 ± 0.77 times/person; UC 0.96 ± 0.85 times/person), a shorter all-cause hospital stay (reduced by 8 days per person) and lower total 6-month medical costs (reduced by US$2682 per patient). These results suggest that the home-based intervention with nursing specialist-led telephone consultations may improve the clinical outcome and provide cost-savings for Chinese patients with heart failure.

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

Background/Purpose: Meningococcal disease, including meningitis and sepsis, usually follows an invasive infection by Neisseria meningitidis, and is a major cause of death and morbidity worldwide. Currently available meningococcal vaccines that consist of pure capsular polysaccharides (serogroups A, C, W-135 and Y) are generally safe and efficacious in adults and children aged ＞2 years. The purpose of this study was to evaluate the immunogenicity, safety and reactogenicity of a single dose of GlaxoSmithKline Biologicals' Mencevax(superscript TM) ACWY vaccine in healthy Taiwanese subjects aged 2-30 years. Methods: This open, single center, Phase Ⅲ study was conducted in Taiwan. A single dose of the Mencevax(superscript TM) ACWY vaccine was administered to subjects aged 2-30 years. Immunogenicity and safety of the vaccine were evaluated after vaccination. Results: The immunogenicity results obtained 1 month after vaccination with Mencevax(superscript TM) ACWY vaccine indicated that the vaccine elicited a good immune response in vaccinees aged 2-30 years. This was both in terms of functional activity directed against meningococcal polysaccharide (A, C, W-135 and Y) as measured by serum bactericidal assay (＞93% activity against all serogroups), and specific IgG concentrations measured by ELISA (＞96% seropositivity to all serogroups). Conclusion: The tetravalent polysaccharide Mencevax(superscript TM) ACWY meningococcal vaccine was well tolerated and immunogenic in subjects aged 2-30 years in Taiwan.

Background. Whether hepatitis B (HB) vaccine– conferred immunity persists into adulthood is unknown. We aimed to investigate long-term HB immunity in adolescents. Methods. In 2004 –2005, 6156 high school students (15–21 years old) who had been vaccinated with plasmaderived HB vaccine as infants were recruited for HB seromarker screening. The immune response to an HB vaccine booster was evaluated in 872 subjects who were seronegative. HB surface antibody (anti-HBs) titers and levels of HB surface antigen (HBsAg)–specific interferon (IFN)–– or interleukin (IL)–5–secreting peripheral blood mononuclear cells (PBMCs; measured by enzyme-linked immunospot assay) were determined 4 weeks later. Results. Although the vaccine remained highly efficacious in reducing the HBsAg positivity rate, 63.0% of the vaccinees had no protective anti-HBs. After the booster, anti-HBs remained undetectable in 28.7% (158/551) of the subjects who had received complete HB vaccination (4 doses) during infancy. We estimated that 10.1% of the total population had lost their HB vaccine– conferred booster response. HBsAg-specific IFN-– or IL-5–secreting PBMCs remained negative in 27.2% (25/92) of subjects after the booster. Conclusions. A notable proportion of fully vaccinated adolescents had lost immune memory conferred by a plasma-derived HB vaccine 15–18 years later. This decay of immune memory may raise concerns about the need for a booster vaccine for high-risk groups in the long run.

Background/Purpose: A prospective study was initiated to study astroviral infections in Taiwan. Methods: A total of 415 stool samples were collected and assayed for astrovirus antigen using an enzyme immunoassay. Results: Twelve (2.9%) stool samples from 12 patients were positive for astrovirus antigen. Most patients (8/12) had watery diarrhea which lasted for 2-6 days. The majority of patients recovered without specific treatment, except for two patients who were treated with antibiotics for possible bacterial infections. One patient developed chronic diarrhea and two episodes were nosocomially acquired. A clustering in the autumn and winter, with a peak in December (5/12), was noted. Growth on Caco-2 cells was performed for four specimens with positive astroviral RT-PCR results, and a characteristic cytopathic effect was observed after 4 days. Astroviral RNA was detected in six stool samples using RT-PCR. Five of six strains were serotype 1 and one strain was serotype 3. Sequence homology among the six strains was between 80.5% and 100%. A higher degree of homology (89.9-100%) was noted in the five strains of serotype 1. A phylogenetic study demonstrated two clusters in our strains and Oxford reference strain types 1 and 2. Conclusion: Our study results provide further information about the prevalence and span of clinical spectra associated with astroviral infections in Taiwan. The current study showed that infection with astroviruses may be an important cause of gastroenteritis, as well as respiratory symptoms, in infants and children in Taipei. [J Formos Med Assoc 2008; 107(4):295-303]

Typical carcinoid tumour of the larynx is extremely rare. We report the case of a 43-year-old man initially diagnosed with typical carcinoid tumour of the larynx, presenting with a foreign body sensation in his throat. Coincidentally, an occult papillary thyroid carcinoma was diagnosed, following detection of a suspicious lymph node on pre-operative imaging studies, and confirmation by neck dissection and subsequent total thyroidectomy. Following surgery and radioiodine therapy for these cancers, the patient was alive, well and free of disease two years later. Typical carcinoid tumour of the larynx with a synchronous occult papillary thyroid carcinoma has not previously been reported. The optimal treatment strategy for this case is also discussed.

Human coronavirus NL63 (HCoV-NL63) is a global respiratory tract pathogen; however, the epidemiology of this virus in subtropical area is not well known. To evaluate the epidemics and disease spectrum of HCoV-NL63 infection in children in Taiwan, we prospectively screened children admitted to the hospital with respiratory tract infection from May 2004 to April 2005. Every enrolled child had a nasopharyngeal aspirate (NPA) sample taken. Quantitative RT-PCR was used to detect 1b gene of HCoV-NL63. A total of 539 NPAs were collected. Seven (1.3%) were positive for HCoV-NL63. All cases were boys younger than 3 years of age and most cases occurred in autumn. Co-infection with other pathogens was observed in three cases. The most common symptoms/signs of HCoV-NL63 infection were cough, fever, and inspiratory stridor. HCoV-NL63 was the most common pathogen (14.7%) in children with croup and was the cause of three cases of croup in October. The odds ratio of croup in children infected with HCoV-NL63 was 43.4 (95% CI 8.1 approximately 233.1). In conclusion, HCoV-NL63 is an important respiratory tract pathogen as the main cause in children admitted to the hospital in Taiwan.

Enhanced molecular surveillance of virulent clones with higher competence can detect serotype switching., From 2003 to 2005, we prospectively collected 118 isolates of pneumococci belonging to 7 serotypes to investigate their competence under the influence of the synthetic competence-stimulating peptides. The degree of competence of the various serotypes differed significantly. Serotype 6B had the highest competence, followed by serotypes 14, 19F, 9V, 23F, 3, and 18C. Isolates belonging to serotype 6B had greater genetic diversity than isolates belonging to serotype 3, which has high genetic clustering. Isolates belonging to serotypes 3 and 18C that were 100% sensitive to penicillin were significantly less competent than isolates belonging to serotypes 6B, 14, 19F, 9V, and 23F, which were frequently resistant to penicillin. Under the 7-valent pneumococcal conjugate vaccine program, enhanced molecular surveillance of virulent clones with higher competence to detect serotype switching will become more important.

We valuated specific cellular and humoral immune response of cases of enterovirus 71 (EV71) infection and correlated immune response with clinical outcome. After obtaining informed consent, we enrolled 30 EV71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of CNS (CNS) involvement and 11 uncomplicated cases. We measured antibodies specific to EV71, lymphocyte proliferation response and EV71-stimulated cellular response of Th1/Th2 cytokines and chemokines. The 7 EV71 cases involving brainstem encephalitis plus pulmonary edema had a significantly lower phytohemagglutinin stimulation index than other cases (p = 0.04). After EV71 stimulation of peripheral mononuclear cells, there was a significant increase in cellular Th1 cytokine (gamma-interferon) and proinflammatroy cytokines. However, cases with pulmonary edema had significantly lower cellular gamma-interferon (p = 0.04), lower cellular IL-1beta (p = 0.04), lower cellular IL-6 (p = 0.04), lower cellular tumor necrosis factor-alpha response (p = 0.04), and lower cellular macrophage inflammatory protein-1alpha (p = 0.04) response compared with other cases. Their titers of EV71 neutralizing antibodies demonstrated no difference among cases. These results suggest lower EV71-specific cellular response may be associated with immunopathogenesis of EV71-related pulmonary edema.

To investigate the pathogens that racing pigeons in Taiwan are exposed to, a total of 3764 pigeons from 90 lofts were analysed by collection of blood samples in the period between October 2000 and September 2001. The haemagglutination inhibition (HI) test was performed to detect antibodies against Newcastle disease virus (NDV), type 2 avian paramyxovirus (APMV-2), and egg drop syndrome '76 virus (EDS-76V). The agar-gel precipitin (AGP) test was used to detect antibodies against fowl adenovirus (FAV), goose parvovirus (GPV), and avian reovirus (REO). The virus neutralisation (VN) test was applied to detect antibodies against the serotypes FAV-1 and FAV-8. A rapid serum agglutination test was applied for the detection of antibodies against Mycoplasma spp. Antibodies to several infectious agents were found, including NDV (43.3%), EDS-76V (19.2%), FAV (0.8%), REO (0.5%), APMV-2 (0.2%), Mycoplasma columbinum (10.3%), M. columborale (7.1%), M. synoviae (1.8%) and M. gallisepticum (1.3%). Antibodies against GPV, FAV-1, and FAV-8 were not detected in any serum sample. NDV seroprevalence was significantly higher in pigeons of more than one year of age than in pigeons younger than one year. ND or EDS-76 seroprevalence of pigeons vaccinated with ND vaccine or EDS-76 vaccine was significantly higher than that of pigeons that did not receive any vaccination.

Background/Purpose: Pneumococcal infection causes high morbidity and mortality in children. Prevention of pneumococcal diseases by effective vaccination is an urgent need. This study evaluated the safety and immunogenicity of heptavalent pneumococcal conjugate (7VPnC) vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) booster dose administered at 15-20 months of age in Taiwanese toddlers. Methods: Fifty-eight healthy Taiwanese toddlers who were primed with three doses of the 7VPnC vaccine in infancy received a booster dose in an open-label, noncomparative trial. Routine oral polio vaccine and diphtheria toxoid, tetanus toxoid, and pertussis vaccine were administered concomitantly. Surveillance for safety was conducted after vaccination. Antibody concentration to each of the seven pneumococcal serotypes was measured before and 1 month after the booster dose. Results: Mild to moderate local reactions were common (45-50%). Fever, fussiness, restlessness, and loss of appetite were the most frequent systemic reactions (31-50%). Before the booster dose of vaccine, 68% (for serotype 18C) to 100% (for serotype 14) of subjects had antibody concentrations ≥0.2μg/mL to different pneumococcal serotypes. After the booster dose, the geometric mean concentration of IgG increased significantly (p＜0.001) for all seven serotypes indicating the induction of immunologic memories. Ninety-eight percent of the toddlers had antibody concentration ≥0.2μg/mL against all serotypes after the booster. Conclusion: The 7VPnC vaccine containing the prevalent serotypes in Taiwan is safe and effective in boosting immunity against pneumococcal disease in Taiwanese children.

Influenza A virus is well known for its capability for genetic changes either through antigen drift or antigen shift. Antigen shift is derived from reassortment of gene segments between viruses, and may result in an antigenically novel virus that is capable of causing a worldwide pandemic. As we trace backwards through the history of influenza pandemics, a repeating pattern can be observed, namely, a limited wave in the first year followed by global spread in the following year. In the 20th century alone, there were three overwhelming pandemics, in 1918, 1957 and 1968, caused by H1N1 (Spanish flu), H2N2 (Asian flu) and H3N2 (Hong Kong flu), respectively. In 1957 and 1968, excess mortality was noted in infants, the elderly and persons with chronic diseases, similar to what occurred during interpandemic periods. In 1918, there was one distinct peak of excess death in young adults aged between 20 and 40 years old; leukopenia and hemorrhage were prominent features. Acute pulmonary edema and hemorrhagic pneumonia contributed to rapidly lethal outcome in young adults. Autopsies disclosed multiple-organ involvement, including pericarditis, myocarditis, hepatitis and splenomegaly. These findings are, in part, consistent with clinical manifestations of human infection with avian influenza A H5N1 virus, in which reactive hemophagocytic syndrome was a characteristic pathologic finding that accounted for pancytopenia, abnormal liver function and multiple organ failure. All the elements of an impending pandemic are in place. Unless effective measures are implemented, we will likely observe a pandemic in the coming seasons. Host immune response plays a crucial role in disease caused by newly emerged influenza virus, such as the 1918 pandemic strain and the recent avian H5N1 strain. Sustained activation of lymphocytes and macrophages after infection results in massive cytokine response, thus leading to severe systemic inflammation. Further investigations into how the virus interacts with the host's immune system will be helpful in guiding future therapeutic strategies in facing influenza pandemics.

To investigate the role of cytokine in the pathogenesis of enterovirus central nervous system (CNS) infections, 14 children with encephalitis (6 infected by enterovirus 71) and 21 children with meningitis (14 infected by echovirus 30 and 7 infected by echovirus 6) were recruited. Serum and cerebrospinal fluid (CSF) specimens were tested for interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a). The results showed that only 1 of 14 (7%) meningitis children has a measurable TNF-a level in CSF. By contrast, 4 of 6 (67%) CSF specimens and 10 of 12 (83%) serum specimens in encephalitis children had detectable TNF-a. Children with meningitis tended to have a higher CSF IL-6 level with borderline significance (378 ′ 207 pg/mL vs. 153 ′ 157 pg/mL; P = 0.075), and had a significantly lower CSF TNF-a level (1.4 ′ 5.1 pg/mL vs. 109 ′ 87 pg/mL; P = 0.003) than children with encephalitis. CSF concentrations of IL-6 and TNF-a tended to be higher in those with confirmed EV71 infections than in other encephalitis children with a borderline statistical significance (P = 0.075 and 0.061. respectively). In conclusion, IL-6 response is more prominent in enterovirus meningitis, whereas TNF-a response is more prominent in enterovirus encephalitis. The difference in cytokine response may be one of the underlying mechanism accounting for different severities of various enterovirus CNS infection.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel SARS-associated coronavirus (SARS-CoV). The clinical characteristics are high fever, rapidly progressive diffuse pneumonitis and respiratory distress. It is highly infectious through intimate contact or direct contact with infectious body fluids. Outbreaks within communities and hospitals have been reported. Development of rapid and reliable diagnostic tools is urgently needed. We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), using whole virus antigen of SARS-CoV. Eighty-six serum samples collected from patients who were hospitalized for other causes were examined to determine the cut-off O.D. value. The cut-off O.D. value was defined as 0.175 by calculating the mean O.D. value of the 86 sera plus 3 standard deviations. To determine the sensitivity and specificity of the ELISA, 56 positive sera and 204 negative sera were tested. The sensitivity was 96.4% and the specificity was 100%. The results suggest that the IgG ELISA using whole virus antigen of SARS-CoV has a high sensitivity and specificity in detecting SARS IgG antibodies. This IgG ELISA is a powerful tool for serodiagnosis of SARS.

Objective. Kawasaki disease (KD) is the most common acquired heart disease in children worldwide. The incidence of KD varies among different countries, with Asian countries supposedly having higher incidences than Western countries. However, the incidence of KD in Taiwan has not been well investigated.Methods. Since the implementation of Taiwan's National Health Insurance (NHI) in 1995, NHI has covered health care for >96% its population. Using the NHI database from 1996 to 2002, we investigated epidemiologic features of KD (International Classification of Diseases, Ninth Revision, code 446.1), the rate of coronary artery aneurysm formation (International Classification of Diseases, Ninth Revision, code 414.11), and the change in incidence during the recent 7 years. We also compared the annual incidences in Taiwan with those reported by other countries.Results. During the 7-year study period, KD occurred most frequently in the summer and least frequently in winter. It is interesting that the highest peak occurred in the summer of 1998 at the same time that Taiwan's enterovirus 71 epidemic was occurring. Ninety-one percent of KD cases occurred in children who were Conclusions. KD in Taiwan occurs more frequently in boys and in the summer months. During the 7-year study period, the annual KD incidence in Taiwan of 66/100000 in children

This study compared safety, tolerability, and immunogenicity of the Oka/Merck varicella vaccine and VARILRIX [Oka-RIT strain SmithKline Beecham Biologicals] in healthy children 12-24 months of age. Subjects were randomized in this double blind study to receive either a single dose of Oka/Merck varicella vaccine, (approximately 50,000 plaque forming units (PFU), Group A or approximately 16,000 PFU, Group B) or 1 dose of VARILRIX, (approximately 40,000 PFU/dose, Group C). Safety profiles in each treatment group were similar. The proportions of subjects achieving a 6-week postvaccination titer> or = 5 gpELISA units in Groups A, B or C were 97.1, 95.2 and 85.6%, respectively.

We studied preexisting immunity to pandemic (H1N1) 2009 virus in persons in Taiwan. A total of 18 (36%) of 50 elderly adults in Taiwan born before 1935 had protective antibodies against currently circulating pandemic (H1N1) 2009 virus. Seasonal influenza vaccines induced antibodies that did not protect against pandemic (H1N1) 2009 virus.

The transmembrane glycoprotein NSP4 functions as a viral enterotoxin capable of inducing diarrhea in young mice. It has been suggested that NSP4 may be a key determinant of rotavirus pathogenicity and a target for vaccine development. Twenty two G1P[6] rotaviruses from babies with and without diarrhea were comparatively analyzed along with reference strains and another 22 Taiwanese human rotaviruses of G and P combination types different from the G1P[6] type. The sequence variations in the NSP4 genes were studied by direct sequencing analysis of the amplicons of reverse transcription-PCR. Two genetic groups could be identified in this analysis. While the majority of these strains were closely related to the Wa strain, the G2 viruses were closely related to the S2 strain. Furthermore, phylogenetic analysis of the NSP4 gene among the G2 rotaviruses revealed three distinct lineages associated with DS-1, S2, and E210, respectively, as has been reported previously for the VP7 gene. However, we found no apparent correlation in the deduced amino acid sequences corresponding to the proposed enterotoxic peptide region between the rotaviruses recovered from individuals with and without diarrhea. The NSP4 gene product being a pathogenic determinant may not be a generalized phenomenon.

Thirteen patients who had 16 episodes of bacteremia were observed between 1993 and 1997 in a pediatric oncology ward with a high background isolation rate of cefotaxime- or aztreonam-resistant gram-negative bacteria. Four blood isolates were Escherichia coli and 12 were Klebsiella pneumoniae , and these isolates harbored extended-spectrum β-lactamases (ESBLs). All episodes of bacteremia were nosocomial, all except one of the episodes occurred in neutropenic patients, and all patients were treated with piperacillin or ceftazidime with amikacin and cefazolin prior to the onset of bacteremia. Nine of 13 patients were receiving extended-spectrum β-lactam treatment when the bacteremias caused by ESBL producers occurred. Molecular studies revealed that four K. pneumoniae SHV-2-producing isolates from 1994 were of the same clone. Other ESBL producers, including six that carried both TEM-1 and SHV-5, five that carried SHV-5, and one that carried SHV-2 alone, were unrelated. In conclusion, SHV-5 was present in 11 of the 16 isolates and coexisted with TEM-1 in 6 isolates. Acquisition of resistance genes probably occurred under antibiotic selection pressure. This study highlights the importance of routine checks for and detection of ESBL producers. Effective therapy against ESBL producers should be considered early for children who have malignancies and neutropenia and who are septic, despite treatment with a regimen that includes an extended-spectrum β-lactam, in a clinical setting of an increased incidence of ESBL-producing bacteria.

Hepatitis B (HB) vaccine provides an uncertain duration of protection and the optimal timing of booster vaccine remains unclear. This study examined the immune response at 10 years of 118 children who had developed protective anti-HB surface (anti-HBs) levels after a primary series of HB immunizations in infancy. All of the children were born to hepatitis B e Antigen (HBeAg)-positive hepatitis B surface antigen (HBsAg) carrier mothers. HB markers in all subjects and cellular immune response in some were determined. A booster was given to all subjects after the collection of samples and another blood sample was collected 4 weeks later. The results showed that a total of 39 (33%) of the children were seronegative for anti-HBs. T-cell proliferative response to HBsAg was noted in 47% of children. On HBsAg stimulation, leukocyte samples from a significantly higher proportion of subjects produced cytokines (81% of T cells produced interleukin-2 [IL-2] and 100% produced IL-5). The booster dose of HB vaccine induced the production of a protective level of anti-HBs (>/=10 mIU/mL) in all subjects. Cellular immunity was augmented with a positive rate of 58%, 90%, and 100% for HBsAg-induced T-cell proliferation, IL-2 production, and IL-5 production, respectively. Although 14 (11.9%) of the subjects were HB core antibody positive at 10 years of age, no new HBsAg carrier was detected. The results of this study show that protection afforded by HB vaccination persisted to the age of 10 years in all vaccinees. Immunologic memory was detected in all subjects including those who had lost their anti-HBs seropositivity. These results suggest that no booster vaccination is needed before 10 years of age. The most sensitive marker of immunologic memory is IL-5 production of T cells. (HEPATOLOGY 1999;29:954-959.)

Because of the interference by maternal antibody before 1 year of age, the Schwarz strain of measles vaccine, which has been routinely used in Taiwan, must be given at 9 months and 15 months of age to ensure an optimal immune response. The AIK-C strain of measles vaccine has been reported to be highly immunogenic. This study evaluated the immunogenicity and safety of the AIK-C vaccine in 9-month-old Taiwanese infants. A total of 135 infants were recruited and were randomly assigned to receive either Schwarz vaccine (68 cases) or AIK-C vaccine (67 cases). Measles antibodies were assayed before and 1 month after the vaccination. Sixty-five (97%) infants who received the AIK-C vaccine seroconverted after the vaccination, whereas the seroconversion rate in those receiving the Schwarz vaccine was 77% (P = 0.001). The incidences of adverse reactions were comparable between the two groups. We conclude that even in 1990s, the failure rate of Schwarz vaccine in 9-month-old infants is still high. The AIK-C vaccine is more immunogenic in infants and its long-term immunogenicity and safety deserve further evaluation.

Objective.Immunologic interference particular to the Haemophilus influenzae type b (Hib) response has been observed with previous acellular pertussis-Hib combination vaccines. To test this hypothesis a clinical trial to assess the safety and immunogenicity of a five-component (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae 2 and 3 [FIM]), pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) when given simultaneously with a lyophilized Hib-tetanus toxoid conjugate vaccine (PRP-T) in infants at 2, 4, 6, and 18 months of age was conducted. The study compared two methods of administration: both vaccines combined in a single syringe and administered as a single injection, or both vaccines administered concurrently but at separate sites of injection.Methods.Healthy 2-month-old infants were enrolled at the National Taiwan University Hospital. DTaP, PRP-T, and oral poliomyelitis vaccine (OPV) were given at 2, 4, 6, and 18 months. Reaction information was collected by telephone 2 days after each vaccination. Serum was collected at 2, 6, 7, 18, and 19 months of age.Results.One hundred thirty-five healthy infants were enrolled in Taiwan, of which 127 (94%) completed the 18-month booster: 68 received the combined vaccine and 67 the separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were reported. Serologic responses were comparable between the groups. Pertussis responses (enzyme-liked immunoabsorbant assay units [EU]/mL) at 7 months were, for combined versus separate, PT (131 vs 105), FHA (116 vs 116), PRN (100 vs 77), and FIM (922 vs 702). At 19 months, pertussis results were, for combined versus separate, PT (216 vs 182), FHA (203 vs 200), PRN (263 vs 197), and FIM (892 vs 732). Only the 7-month PT response in the combined group was significantly higher (combined 131 EU/mL vs separate 105 EU/mL). After the third dose (age 6 months), all subjects achieved serologic serum antibody levels indicative of protection against Hib, diphtheria, tetanus, and poliovirus types 1, 2, and 3. In fact, 96% of children had anti-PRP levels indicative of protection (≥0.15 μg/mL) against Hib after only two doses. At 7 months, anti-PRP geometric mean titer values were 11.8 μg/mL in the combined group compared with 13.0 μg/mL in the separate group. The anti-PRP geometric mean titers after the 18-month booster were 58.5 μg/mL in the combined group versus 55.3 μg/mL in the separate group.Conclusion.The five-component DTaP vaccine may be combined with PRP-T vaccine without clinically significant immunologic interaction when given in a 2-, 4-, 6-, and 18-month schedule.

Background A combined diphtheria-tetanus-whole cell pertussis-hepatitis B (DTPwHB) vaccine might facilitate the achievement of universal vaccination of infants against hepatitis B. Methods A double blind, randomized, two-armed, single center study was undertaken to evaluate the immunogenicity and reactogenicity of combined tetravalent DTPwHB vaccine, with two dosages of hepatitis B component (10 microg and 5 microg). The combined vaccine was tested in the context of a simplified vaccination schedule at 1.5, 3.5 and 6 months of age, to 120 healthy infants born to hepatitis B surface antigen-negative mothers after priming with one dose of hepatitis B vaccine (10 microg) at birth. Antibodies to each antigenic component were measured from blood samples collected immediately after birth, pre- and postvaccination blood samples. Results The reactogenicity profiles were similar in the two groups. No serious adverse events were reported. One month after completion of the four-dose vaccination schedule, all subjects except one in Group 1 (10 microg) had protective titers of anti-HBs (10 mIU/ml). At this time the geometric mean titer in Group 1 (10 microg) was higher than that observed in Group 2 (5 microg), 696 vs. 488 mIU/ml (P = 0.19). One month after three doses all subjects in both groups had protective antidiphtheria titers and antitetanus titers. The vaccine response rate to the Bordetella pertussis component of the vaccine was 88.0% in Group 1 and 96.2% in Group 2 (P = 0.86). Conclusion Both combined tetravalent vaccines are safe and immunogenic when administered to infants born to a hepatitis B surface antigen-negative mother, with a 10-microg dose of priming hepatitis B vaccine at birth. This combined tetravalent DTPwHB vaccine may play an important role to promote integration of HB vaccine into the Expanded Program of Immunization in hepatitis B-endemic areas.

Long-term persistence of hepatitis A virus (HAV) serum antibody in vaccinated children has not been demonstrated in previous studies. To study the long-term immunogenicity to HAV vaccine, three doses of strain HM 175 HAV vaccine with 360 enzyme-linked immunosorbent assay units were administered to 107 children, aged from 1.0 to 6.8 years, at 0, 1, and 6 months. The administration of one vaccine dose induced seropositivity (anti-HAV titer > or = 20 mIU ml-1) in 95% of all vaccinees at month 1. All subjects remained seropositive until month 6. The titers of HAV antibody remained above 20 mIU ml-1 in all subjects followed up to 60 months. The geometric mean titer (GMT) reached its peak (3802 mIU ml-1) at month 7, i.e. 1 month after the booster dose, and then declined until the end of follow-up at month 60 (661 mIU ml-1). A trend of higher GMT in female subjects persisted up to month 60. The changes of the GMT over time were best described by the regression equation: log (GMT) = 3.26-0.08 x (age in years) (r = -0.95, P = 0.014). According to this equation, the geometric mean concentration would reach 20 mIU ml-1 at around 24.5 years after the beginning of vaccination. In conclusion, those who completed the recommended three-dose inactivated HAV vaccination series remained seroprotective for at least 5 years. Theoretically, such a vaccination program can provide a protective period of over 20 years in children. This paper may be the first to describe at least 5-year immunogenicity of inactivated HAV vaccination in healthy children.

To investigate the clinical significance of mutation in hepatitis B virus (HBV) surface gene, DNA sequence analysis of the "a" determinant was performed on sera from 27 carrier children with immunoprophylaxis, their mothers, and 21 carriers without vaccination. A precore mutant (G to A) at nucleotide 1896 was detected in sera from 11 carriers without vaccination. Mutations in the "a" determinant were detected in 6 (22%) of the vaccinated children. Four HBV strains showed a Gly-to-Arg mutation at the 145th codon of the surface gene. Amino acid substitutions at amino acid 133 and 144 were noted in the other 2 children. Only 1 mother had the same predominant strain of mutant virus as her child. These observations indicate that immune pressure exerted by immunoprophylaxis at birth may select for a mutant virus.

In order to understand the infection status of human herpesvirus 7 (HHV-7) in Taiwan and clarify the serological cross-reactivity between HHV-7 and HHV-6, a longitudinal study was carried out in 52 infants from whom 9 sera were available from birth to 6 years of age. All sera were tested for antibodies against HHV-6 and HHV-7 by indirect immunofluorescence assay. HHV-7 infection was not seen before 6 months of age and gradually emerged thereafter, reaching a cumulative rate of 28.8%, 67.3%, 73.1 %, 78.8%, 82.7%, and 86.5% by the ages of 1. 2, 3, 4, 5 and 6 years, respectively. Primary HHV-6 infection induced a reactive HHV-7 antibody in 10/28 (35.7%) cases with a titre of no more than 10. Twenty-eight children (53.8%) were infected by HHV-6 earlier than HHV-7. while eight (15.4%) were infected by HHV-7 earlier than HHV-6. In summary, HHV-7 infected children later than HHV-6. A one-way cross-reaction of HHV-7 serology by HHV-6 was revealed and a titre of 20 is appropriate for defining HHV-7 infection.

Objective: To investigate the safety, immunogenicity, and efficacy of a simplified hepatitis B vaccination schedule. Methods: The second dose of hepatitis B vaccine and the first dose of diphtheria-tetanus-pertussis (DTP) vaccine were given simultaneously at age 6 weeks. The second dose of DTP vaccine was given at age 3.5 months. The third dose of DTP vaccine and the third dose of hepatitis B vaccine were given at age 5.5 months. One hundred three infants (group A) born to mothers without hepatitis B surface antigen (HBsAg) received DTP with whole-cell pertussis vaccine. Fifty-five infants (group B) born to mothers with HBsAg and hepatitis B e antigen received DTP with acellular pertussis vaccine. Results: By age 9 months, none of group A and 4 (7%) group B infants were seropositive for HBsAg. The protective efficacy against the hepatitis B carrier state in these infants at high risk was 92%. Antibody to hepatitis B surface antigen was 10 mIU/ml or greater in 99 (96%) of group A infants and in 50 (91%) of group B infants. Both the acellular and whole-cell DTP vaccines were immunogenic, and the incidences of adverse reactions were within an expected and acceptable range. Conclusions: The simplified vaccination schedule to integrate the hepatitis B vaccine into the Expanded Programme of Immunization was safe, immunogenic, and effective. This schedule may improve vaccine compliance and be applied to DTP and hepatitis B combination vaccines now under investigation. (J Pediatr 1997;130:981-6)