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BackgroundKawasaki disease (KD) affects mainly children younger than 5 years of age, leading to coronary artery lesions, and even to life-threatening myocardial infarction. In Taiwan, KD was encountered for the first time in 1976; then, it continued to occur in increasing numbers.MethodsFor the survey of epidemiological features of KD in Taiwan, we conducted five nationwide questionnaire hospital surveys in 1987, 1992, 1994, 2001, and 2008, respectively. In each survey, a special questionnaire form, together with a request letter and diagnostic guidelines for KD, was sent to the chairman of the Department of Pediatrics of all hospitals with 100 or more beds in Taiwan.ResultsKD patients increased to a total of 14,399 patients by 2007, with the highest number of 1018 in 2001, and the highest incidence of 66.24 per 100,000 children

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.

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]

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.

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.

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

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.

A second generation acellular pertussis vaccine (component pertussis vaccine) containing purified pertussis toxin (PT) and filamentous hemagglutinin (FHA) was tested for its immunogenicity and safety in 2-month-old infants in comparison with first-generation acellular and whole-cell pertussis vaccines. At the ages of 2, 4, 6, and 18 months, respectively, 350 subjects were inoculated one dose of pertussis vaccine, which was combined with diphtheria and tetanus toxoids. Both acellular and component vaccines elicited significantly much fewer local and systemic reactions than whole-cell vaccine did. Besides, although not reaching statistical significance, the component vaccine was less reactogenic than the acellular vaccine. After each dose of the primary immunization, antibodies against PT and FHA were much higher in acellular and component pertussis vaccinees than in whole-cell vaccinees. However, at 18 months of age, just before the booster dose, both anti-PT and anti-FHA declined very close to, or even lower than, the prevaccination levels in all three groups and then responded rapidly to a booster dose to attain high levels. The booster responses were also significantly higher (P

The effect of local massage on adverse reactions and immunogenicity of diphtheria-tetanus-pertussis vaccine was investigated. After diphtheria-tetanus-pertussis vaccination 327 infants were either massaged or not, and adverse reactions were evaluated. Local pain and fever were more frequent in the massage group. The extra febrile episodes from massage were mild (38-39 degrees C). For evaluation of the antibody responses, 124 infants were recruited into massage or nonmassage cohorts and antibody production was measured at 2, 6, 7, 18 and 19 months of age, respectively. Subjects in the massage group developed significantly higher antibodies against filamentous hemagglutinin at 6 and 7 months of age, pertussis toxin at 6, 7, 18 and 19 months of age, pertussis agglutinogen at 18 and 19 months of age and those in the nonmassage group. Local massage after diphtheria-tetanus-pertussis vaccination was associated with better immunogenicity and more adverse reactions, including low grade fever and local pain, which were mild and not particularly disturbing.

Serum HBV DNA from infants and children with fulminant hepatitis B (FHB) or acute self-limiting hepatitis B (AHB) and patients believed to be contamination sources was amplified by polymerase chain reaction (PCR) followed by direct sequencing of the precore region. A precore mutation from G to A at nucleotide 1896 was found in 5 of 14 FHB patients and in 3 of 10 AHB patients. Among the 10 infants who developed hepatitis during the first 6 months of age, the precore mutation was detected in only 2 of 7 with FHB and in 1 of 3 with AHB. In 1 infant with FHB, a shift from wild type to precore mutant predominance occurred in the serum virus population during the incubation period. Thus, the precore mutation is neither necessary nor sufficient to cause FHB in childhood, although its contributory role cannot be excluded. Factors other than precore mutations may be important in the pathogenesis of FHB.

This study was aimed to evaluate the efficacy and immunogenicity of combined hepatitis B vaccination with plasma-derived vaccine (PDV) and recombinant vaccine (RV). A total of 329 infants was recruited, including 224 high-risk infants born to hepatitis B e antigen-positive mothers and 105 low-risk infants born to hepatitis B e antigen-negative mothers. The high-risk infants received four doses of hepatitis B vaccine at 0, 1, 2 and 12 months of age with five different schedules. Group A1 and A2 infants were vaccinated with PDV as the first dose and RV (SB vaccine for group A1, MSD vaccine for group A2) as the remaining three doses. Group B1 and group B2 infants were vaccinated with PDV as the first two doses and RV (SB vaccine for group B1, MSD vaccine for group B2) as the remaining two doses. Group C infants received four doses of PDV. Low-risk infants were vaccinated with PDV at birth, and RV at 1 and 6 months of age (group D1, using SB vaccine; group D2, using MSD vaccine). At completion of vaccination schedules, 20 of 224 high-risk infants (9%) were positive for hepatitis B surface antigen. The overall protective efficacy was 90%. Hepatitis B surface antibody (anti-HBs)-positive rate ranged between 94 and 100% among the remaining infants. The protective efficacy and immunogenicity were similar among groups except that the mean level of anti-HBs in group C, D1 and D2 infants tended to be lower than that of the other four groups. To ensure an optimal immune response, four doses of vaccine are recommended in high-risk infants when two types of vaccine are to be used in combination.

The clinical presentations of cholestasis in infancy caused by neonatal hepatitis and biliary atresia are very similar. Diagnosis may be difficult on many occasions, but the surgical treatment of biliary atresia should be performed as early as possible. We established a 3-day workup protocol for the differential diagnosis of biliary atresia and neonatal hepatitis and compared the diagnostic accuracy, sensitivity, specificity, and predictive values of various methods. One hundred and twenty-six infants, including 84 with neonatal hepatitis (age, 65.1 +/- 24.1 days) and 42 with biliary atresia (age, 60.3 +/- 31.1 days), were studied prospectively from July 1982 to December 1990. The diagnostic accuracy of various methods was as follows: liver histology, 96.8%; color of duodenal juice, 91.6%; peak radioisotope count in duodenal juice, 84.2%; ultrasonographic examination of the hepatobiliary system, 80.2%; and persistence of clay-colored stool, 80.2%. After stepwise logistic regression, the diagnostic methods of significance were liver biopsy, color of duodenal juice, abdominal ultrasonography, and stool color. However, stool color and the onset of jaundice could not differentiate severe neonatal hepatitis from biliary atresia. The diagnostic methods of significance then were liver biopsy and duodenal juice color. With this 3-day protocol, no biliary atresia was missed although four cases of neonatal hepatitis were misdiagnosed, resulting in unnecessary laparotomy; we found an overall diagnostic accuracy of 96.8%. We conclude that this 3-day diagnostic protocol is very helpful in the differential diagnosis of neonatal hepatitis and biliary atresia. Liver histologic examination is the most reliable single test for the differential diagnosis.

Fifty-three children who failed to respond to four doses of plasma hepatitis B (HB) vaccine (anti-HBs titre10 IU l-1) were divided into two groups and received revaccination with either three doses of recombinant HB vaccine (10 micrograms/dose, by 0, 1, 6 month schedule; group A) or two additional doses of plasma HB vaccine (5 micrograms/dose, by 0, 1 month schedule; group B) respectively. Thirty-two vaccinees in group A had a response rate (with anti-HBs10 IU l-1) of 53.1% (17/32), 87.5% (28/32), and 100% (32/32) after first, second and third doses of the vaccine respectively. Twenty-one vaccinees in group B had a response rate of 61.9% (13/21) after two additional doses of plasma vaccine. High anti-HBs titres (1000 IU l-1) were noted in 50% of the vaccinees in group A after three doses of vaccine. Comparing anti-HBs response between group A and group B after two additional doses of HB vaccine, group A had a higher anti-HBs titre (geometric mean titre 104.7 IU l-1 versus 75.9 IU l-1) along with a better seroconversion rate (87.5 versus 61.9%). However, the differences in vaccine dose between the two groups may also be a contributory factor. Our findings indicate that three doses of recombinant HB vaccine were invariably effective in eliciting a good immune response in previous non-responders to the four doses of plasma HB vaccine. Therefore, it is speculated that these young vaccinees who did not respond to four doses of plasma HB vaccine may not be real non-responders, but hyporesponders.

To determine the HLA-linked immune response gene that controls low responsiveness to hepatitis B surface antigen (HBsAg), HLA typing was performed in 33 initial non-responders (male:female = 23:10, age 1.5–46 years) who had poor antibody response (anti-HBs < 10 mIU ml−1) after four doses of plasma-derived hepatitis B vaccine. Of 33 initial non-responders, 26 received two additional doses of either the same vaccine (n = 18) or recombinant hepatitis B vaccine (n = 8) and returned for anti-HBs measurement. At 1 month after the sixth dose, anti-HBs was still

Background/Purpose In influenza B infection, viral load is believed to be related to the severity of clinical illness. The correlation between viral load and symptoms is not known. We conducted a study to assess the relationship between virus load and clinical features in children infected with influenza B, in the hope that clinical features could be used as surrogate markers of viral load to guide treatment. Methods Between December 2006 and February 2007, 228 patients with fever and respiratory symptoms were prospectively enrolled in our tertiary hospital-based study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine viral load. Results Real-time RT-PCR was positive for influenza B in 76 patients. Using virus culture as the gold standard, the sensitivity and specificity were 95% and 87%, respectively. Influenza culture positive rate significantly correlated with viral load ( p = 0.03). The median copy number of influenza B virus in the 76 RT-PCR positive patients was 9735 copies/ml (range 4.8×10 1 –2.0×10 6 copies/ml). Samples obtained later in the clinical course tended to have lower viral load ( p = 0.7), while patient age ( p = 0.72) and fever duration ( p = 0.96) positively related to viral load. In patients >3 years of age, myalgia was related to statistically lower viral loads (14300 vs. 1180; p = 0.025). Patients with chills tended to have higher viral loads (72450 vs. 7640; p = 0.1). Patients with abdominal pain tended to have lower viral loads (1998 vs. 12550; p = 0.06). Conclusion Culture rate positively correlated with viral load. Patients with myalgia had a lower viral load.

Brain abscess and subdural empyema are the 2 most common forms of intracranial pyogenic infections. Predisposing factors and etiological agents may change with time. This study examined the epidemiological features of these conditions.The medical records of all inpatients with a diagnosis of brain abscess or subdural empyema from 1998 to 2007 were reviewed. The diagnosis was confirmed by imaging study or operative findings.151 episodes of brain abscess were diagnosed in 150 patients, and 10 patients had subdural empyema. The incidence of brain abscess fluctuated over time, while that of subdural empyema remained stable. The mean +/- standard deviation age of patients with brain abscess was significantly greater than that of patients with subdural empyema (48.5 +/- 19 years vs 25.4 +/- 24 years; p = 0.004). The number of patients with hematogenous brain abscess increased from 7 in 1998 to 2002 to 19 in 2003 to 2007, while that of those with infection related to operation decreased from 10 to 5. Most subdural empyema was related to bacterial meningitis (4 of 10). Etiological agents were identified in 53% of brain abscesses, including Enterobacteriaceae spp. (21.3%), Streptococcus spp. (20%), and mixed pathogens (17.5%). Klebsiella pneumoniae was the most common enteric bacteria isolated (15.3%), especially in patients with diabetes mellitus, but was not observed in children younger than 18 years.In contrast to western countries, K. pneumoniae plays an important role in intracranial pyogenic infections in Taiwan. The pathogens and routes of infection are different between children and adults.

Cellular immunity to HBcAg was studied in hepatitis B virus carrier children and neonates born to hepatitis B virus carrier mothers. A significant proliferative response of peripheral blood mononuclear cells to HBcAg was found in 5 of 10 children with elevated ALT levels but in none of the nine HBeAg-positive children with normal ALT levels. HBeAg but not HBsAg was detected in cord blood of 9 of 10 neonates born to HBeAg-positive carrier mothers, suggesting exposure of these neonates to HBeAg in utero. However, cord mononuclear cells from neonates born to HBeAg-positive carrier mothers did not show a significant change in the proportion of suppressor and helper T-cell subsets or proliferative response to HBcAg. Nor did they produce interleukin-2 receptor after being cocultured with HBcAg. The unresponsiveness of peripheral-blood mononuclear cells or cord mononuclear cells to HBcAg was not reversed by CD8+ cell depletion. Although cord blood mononuclear cells from neonates born to carrier mothers positive for antibody to HBeAg also did not respond to HBcAg, we encountered an infant, born to a carrier mother positive for antibody to HBeAg, who contracted acute hepatitis B at 2.5 mo of age. The baby's peripheral-blood mononuclear cells showed a significant proliferative response to HBcAg. These results support the view that transplacental maternal HBeAg probably induces a specific unresponsiveness of helper T cells to HBcAg and HBeAg in the neonates born to HBeAg-positive carrier mothers. This specific helper T cell tolerance could be maintained throughout the early replicative phase of carrier state but might break someday with the appearance of raised ALT level.

The prevalence of cytomegalovirus (CMV) antibody was studied in 966 children in 1984 and 927 children in 1989. The overall prevalence rate of CMV antibody was 59% for children in 1984 and 46% for children in 1989 (P less than 0.05). In both study years, the prevalence rate of CMV antibody was about 70% in infants under 6 months of age, declined to a trough between the ages of 6 and 12 months, and then increased to 40-50% between 1 and 4 years of age. The rate of CMV antibody for children above 4 years in 1984 increased steadily with age and reached 82% by 12 years. In contrast, the prevalence rate in 1989 remained at the level of 40-50% from age 4 to 10 years. It was followed by a sharp increase after 10 years of age and reached 84% at 12 years old. The seropositive rate in each of the 5-, 6-, 8-, 9-, and 10-year-old groups was higher in 1984 than that in 1989. These observations indicated that the prevalence rate of CMV antibody is decreasing in children. This change may be related to various socioeconomic factors, especially the less crowded family conditions in recent years.

A seroepidemiological study was carried out to explore the risk factors of a measles outbreak that occurred among school children at a rural village (Li-Tse) in Taiwan. Among the 1166 participants, the percentage susceptible before the outbreak was 10.5% (122/1158) which was estimated as the sum of measles IgG-negative (29/1158) and IgM-positive (93/1166) individuals. Among 340 vaccinated children, 16 (4.7%) were measles IgM-positive and 10 (2.9%) were measles IgG-negative; therefore the vaccine failure rate was estimated to be 7.6% (26/340) and vaccine efficacy was 79.7% (95% confidence interval [CI] : 65.0-88.5). The most important risk factors for acquiring measles infection were the presence of other measles cases in the family (Odds Ratio [OR] = 32.5, P = 0.002) and the presence of more than two cases in a class (OR = 29.1, P = 0.003). The physician reporting rate was 6.1% (4/66), and the sensitivity of passive measles surveillance was only 4.3% (4/93) by active serosurvey. A concomitant rubella epidemic also amplified the inaccuracy of a passive reporting system based only on clinical diagnosis. Five children developed measles IgM but did not experience any symptoms, indicating that asymptomatic measles infection can occur. Our experience has highlighted three important areas for future measles elimination: (1) the need for serological evaluation of vaccinees, particularly those who were born during the introduction of mass immunization; (2) improvement in measles vaccine efficacy; and (3) further investigations on the role of asymptomatic transmission and susceptibles who remain after mass immunization.

Thirty-nine children without previous cytomegalovirus (CMV) infection received blood transfusion in the National Taiwan University Hospital. The overall transfusion-acquired CMV infection rate was 36% (14/39). Donor CMV seropositive rate was 70%. None of the nine children who had received seronegative blood became infected, in contrast to 14 of the 21 children (67%) who had received seropositive blood (P = 0.002). Another significant risk factor associated with CMV infection was the use of fresh blood: 13 of 15 (87%) with fresh seropositive blood were infected, in contrast to one of six (17%) with "old" seropositive blood (P = 0.01). Most of the fresh blood was used within 24 hours. This blood processing method was shown to account for the extremely high rate of CMV infection in those who had received fresh seropositive blood. The results indicated that the incidence of CMV infection can be reduced by avoiding the use of fresh blood, especially blood less than 24 hours old. For such a population in Taiwan with high prevalence of positive CMV antibody, this approach was more applicable than screening donor blood for CMV antibody.

Bell's palsy is not uncommon in children. This study was performed to evaluate the epidemiology of Bell's palsy in the northern Taiwanese pediatric population, and the effectiveness of corticosteroid treatment.The medical records of pediatric patients with a primary diagnosis of facial palsy from April 2002 through March 2007 were reviewed. Patients with secondary facial palsy were excluded from the analysis.289 episodes of facial palsy were identified and the clinical findings of 134 episodes among 132 patients were assessed. The median +/- standard deviation age was 9.9 +/- 4.9 years, and 58.2% of patients were girls. Children were more likely to have episodes of Bell's palsy during the cold season, with a peak in January. The left (67 episodes; 50.0%) and right (64 episodes; 47.8%) facial nerves were involved with similar frequency. Common symptoms were postauricular pain (11.2%) and facial hypoesthesia (9.0%). Of 51 episodes of Bell's palsy with complete follow-up, corticosteroids were given for 44 episodes. Thirty eight patients (86.4%) given corticosteroids had complete recovery and 4 patients (57.1%) recovered without corticosteroids. Rates of complete recovery did not differ significantly between the 2 groups (p = 0.08). There were no significant differences in the recovery rate between early (or = 3 days) and late (4-7 days) administration.In northern Taiwan, childhood Bell's palsy peaks from January through March. The majority of children with Bell's palsy recovered completely. There was no significant effect of corticosteroid treatment for children with Bell's palsy.

The epidemiology of coxsackievirus has rarely been investigated in Taiwan. This study was performed to ascertain the epidemiological and clinical characteristics of coxsackievirus infections in Taiwan.457 patients treated at a medical center in northern Taiwan who were positive for coxsackievirus were enrolled in this retrospective study. Patients' medical charts were reviewed for clinical diagnosis, physical examination, laboratory findings, and clinical manifestations.Three serotypes of coxsackievirus A (A9, 5.3%; A10, 7.2%; A16, 87.5%) were identified among 265 patients, 27.4% of whom were admitted to hospital. The mean (+/- standard deviation [SD]) duration of fever and hospital stay was 2.6 +/- 0.5 days and 4.0 +/- 2.1 days, respectively. Complications were noted in 14 patients (5.3%), all of which involved the central nervous system (CNS). All 6 serotypes of coxsackievirus B (B1, 2.6%; B2, 7.8%; B3, 55.7%; B4, 2.1%; B5, 12.5%; B6, 1.0%; non-typable, 18.2%) were identified in 192 patients, 45.3% of whom were admitted to hospital. The mean (+/- SD) duration of fever and hospital stay was 4.1 +/- 1.0 and 3.4 +/- 0.9 days, respectively. Thirty seven patients (19.3%) had complications, including 34 with CNS involvement. Patients with coxsackievirus B infection had higher hospital admission rates (p0.001), more CNS involvement (p0.001), and longer fever duration (p0.001) than those with coxsackievirus A infection. Patients with coxsackievirus A infection tended to have more skin manifestations (p0.001) and oral ulcers (p0.001).The most common serotypes were coxsackieviruses A16 and B3. Patients with coxsackievirus B infection were more likely to be admitted to hospital, had longer fever duration, and more CNS involvement than patients with coxsackievirus A infection.

Campylobacter infection is recognized as a major cause of acute enteritis in humans. The clinical characteristics may vary in different countries. This study investigated the clinical manifestations of pediatric Campylobacter enteritis in a medical center in northern Taiwan.This was a retrospective review of Campylobacter enteritis infections at National Taiwan University Hospital, Taipei, Taiwan, from January 2000 to December 2006. All children who tested positive for Campylobacter, isolated from stool samples, were included in the study. Data collected and evaluated included the species of Campylobacter, age, gender, underlying disease, travel history, clinical manifestations and laboratory data.A total of 104 patients had enteric campylobacteriosis. Campylobacter coli was grown from 24 patients (23.1%), while Campylobacter jejuni was found in 80 patients (76.9%). More than half of the infections (60.6%) occurred in children less than 5 years old. The male-to-female ratio was 2.46:1. Fifteen patients had underlying diseases (14.4%), such as hematologic malignancy, solid organ transplantation and liver cirrhosis. Watery diarrhea (93.2%), abdominal pain (92.0%), fever (81.2%), and vomiting (46.1%) were the most common clinical manifestations. Three episodes of campylobacteriosis appeared to be imported from Southeast Asia and 3 were acquired nosocomially. One patient, who did not have any underlying disease, developed Campylobacter bacteremia. No Guillain-Barre syndrome was noted in our patients and none of our patients died due to campylobacteriosis. While both diseases had similar clinical manifestations, infections caused by C. coli seemed to be more severe than those caused by C. jejuni, as evidenced by a higher incidence of decreased activity and pus cells in the stool in patients infected with C. coli.Even in patients with bacteremia or underlying disease, enteric campylobacteriosis usually runs a benign course regardless of treatment with antimicrobial agents in children in northern Taiwan.

Twenty-seven children with non-A, non-B hepatitis were studied with regard to their clinical, serologic, and histologic features. In contrast to adult patients, non-A, non-B hepatitis developed in most pediatric patients (19 out of 27) in the absence of identifiable parenteral exposure, probably because of fewer chances for exposure of children to blood or blood-contaminated products. Perinatal transmission was considered possible in one of the patients. Fulminant hepatitis had occurred in six patients, two of whom died. It is noteworthy that fulminant hepatitis usually occurred in children with sporadic non-A, non-B hepatitis. The progression to chronic hepatitis after acute illness is less likely in children than in adults. Chronic hepatitis developed in four patients. Two of these were asymptomatic at presentation, suggesting that in some patients, non-A, non-B hepatitis infections may remain undetected and progress t o chronic hepatitis. Liver histologic examination was performed in 11 patients. There were no characteristic histologic findings which could differentiate non-A, non-B from B hepatitis. Antibodies to hepatitis C virus (anti-HCV) were tested i n 22 of the 27 patients and 8 (36%) were seropositive for anti-HCV.

Ten cases of pediatric fulminant hemophagocytic syndrome, encountered between 1986 and 1989, are described. They occurred in the summer, and the patients presented with fever, jaundice, hepatosplenomegaly, pancytopenia, coagulopathy, and abnormal liver function. Bone marrow studies revealed infiltration by atypical T-lymphoid cells, rare B immunoblasts, and mature histiocytes with hemophagocytosis. Initially, histiocytic medullary reticulosis was suspected in six cases. The clinical course was characterized by rapid deterioration, with a mean period of 16 days from onset of fever to death. The main causes of death were coagulopathy with multiple organ failure and opportunistic in-fection. In seven of eight cases studied by serologic assay and Southern blot hybridization, acute or active Epstein-Barr virus (EBV) infection was documented. It is suggested that an atypical or fulminant form of primary EBV infection distinct from classic infectious mononucleosis was prevalent in previously healthy children in Taiwan. Younger age involvement and seasonal clustering were characteristic of the disorder described.

Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination.

Objectives:18F-Fluorodeoxyglucose positron emission tomography can detect cervical metastases before they are palpable. However, false positive results are not uncommon. This paper reports the use of ultrasound-guided fine needle aspiration to determine the nature of impalpable cervical nodes that are positive on positron emission tomography scanning.Methods:Ultrasound-guided fine needle aspiration was performed in 10 cancer patients with suspicious cervical nodes revealed by positron emission tomography scan. Clinical data were retrospectively reviewed.Results:The underlying cancers included lung cancer (three patients), nasopharyngeal carcinoma (two), oesophageal cancer (two), buccal cancer (one), bladder cancer (one) and Langerhan's histiocytosis (one). The lymph nodes were located in the supraclavicular region in four patients, the level II region in four, the level IV region in one and the accessory chain in one. Cytological examination was positive for malignant cells in eight patients, all of whom received salvage treatment. Two of these patients died of distant metastases. Cytological examination revealed a benign or reactive lesion in two patients, who at the time of writing were alive and well, 19 and 36 months after examination.Conclusions:Ultrasound-guided fine needle aspiration is a minimally invasive procedure which enables cytological examination of suspicious cervical lymph nodes detected by positron emission tomography scanning, allowing further treatment to be planned.

This study aimed to evaluate the efficacy and safety of clarithromycin and erythromycin in the treatment of community-acquired pneumonia in children.Children with community-acquired pneumonia were randomly assigned to receive 10-day regimens of either clarithromycin 15 mg/kg/day, twice a day, or erythromycin 30-50 mg/kg/day, four times daily.A total of 97 children entered this study, including 26 with Mycoplasma pneumoniae infection, 15 with Chlamydia pneumoniae infection, and 6 with mixed mycoplasma and chlamydia infections. Fifty and 47 children received clarithromycin and erythromycin treatment, respectively. Three children withdrew from the study because the identified pathogens were resistant to the study drugs. All 47 children with mycoplasma or chlamydia infection were cured clinically. Delayed defervescence, defined as a fever lasting for more than 72 h after treatment, was observed in 4 of 22 clarithromycin-treated children (18%) and in 3 of 15 erythromycin-treated children (20%) [p0.05]. Gastrointestinal side effects, including vomiting, abdominal pain and diarrhea, were observed in 3 of 50 children (6%) receiving clarithromycin and in 11 of 49 children (22%) receiving erythromycin (p=0.039). Excluding children with abnormal pretreatment liver function, abnormal liver function after treatment was observed in only one child, treated with erythromycin. Post-treatment eosinophil and platelet counts were significantly elevated after treatment in both groups.Clarithromycin showed efficacy equivalent to erythromycin for the treatment of mycoplasma or chlamydia pneumonia in children. However, the tolerability of clarithromycin was superior to that of erythromycin.

During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acinetobacter baumannii is one of the common nosocomial pathogens, and the emergence of multidrug-resistant A. baumannii (MDRAB) is a therapeutic problem. We describe the clinical characteristics and outcomes of MDRAB colonization/infection in pediatric patients at the National Taiwan University Hospital.Fifty two pediatric patients with 205 MDRAB isolates collected between April 2000 and December 2005 were included for investigation of their clinical characters, presentations, and outcome.Among these 205 isolates, 20 (9.8%) were from sterile body sites (11 from blood, 8 from catheter tips, and 1 from ascites), 154 (75.1%) from respiratory sites, 18 (8.8%) from skin or wound pus, 5 (2.4%) from urine, and 8 (3.9%) from other sites. The mean age was 6 years. The common underlying diseases were haematological or oncological diseases (n = 15, 28.8%), neonatal disorders (6, 11.5%), cyanotic congenital heart diseases (10, 19.2%), neurology disorders (12, 23.1%), and gastrointestinal tract disorders (3, 5.8%). Seventeen patients (32.7%) had received major surgery, and 48 (92.3%) had used ventilators. Fourteen patients (26.9%) had neutropenia and 46 (88.5%) had used broad-spectrum antibiotics. There were 31 patients (59.6%) with suspected or proven MDRAB infections, including sepsis (9 patients), pneumonia (19), wound infections (3), urinary tract infections (2), peritonitis (1), and perineal infection (1). Seven (77.8%) of the 9 sepsis patients died. The overall mortality rate was 42.3% (22 cases).The threat of MDRAB has been recognized in our hospital for several years. Host defense deficiencies, prolonged intensive care unit hospitalizations, and prior broad-spectrum antibiotic use play a major role in MDRAB infection and colonization.

Respiratory syncytial virus (RSV) is an important pathogen in children less than 2 years old. However, there is limited epidemiological data about RSV infection in Taiwan. This study aimed to investigate the clinical, epidemiological, virological, and economical aspects of RSV infections in Taiwan.We collected data of children with positive RSV respiratory specimens at the Laboratory of Virology, National Taiwan University Hospital, between January 2001 and December 2005. Medical charts were reviewed retrospectively.892 children in whom acute bronchiolitis was the predominant diagnosis (60.7%) were enrolled. Compared with those without underlying disease (n = 630), children with underlying disease (n = 262) were older (11 vs 9 months), required longer oxygen therapies (7 vs 4 days), were more likely to have lower respiratory tract involvement (96.2% vs 92.3%) and intensive care unit stays (49.0% vs 9.4%), endotracheal intubations (21.0% vs 2.0%), ribavirin use (35.0% vs 1.4%), and had higher medical costs (US$ 1250 vs 688), and nosocomial infection (24.8% vs 1.0%). Compared with those without endotracheal intubation (n = 824), cases requiring endotracheal intubation (n = 68) had higher rates of underlying diseases (80.9% vs 25.1%), especially congenital heart diseases (45.6% vs 8.1%), chronic lung disease (13.2% vs 3.2%) and neurological disorders (17.6% vs 3.5%). There was a biennial pattern with peaks in the spring and fall. Medical cost was estimated to be US$ 250,000 annually in our hospital.In children with underlying diseases, RSV infection is associated with significant morbidity, and even mortality. Nosocomial infections appear to be an important cause of RSV transmission. The seasonality of RSV infections in Taiwan showed a biennial pattern with peaks in spring and fall.

Viridans streptococci (VS) are part of the normal flora of humans, but are fast emerging as pathogens causing bacteremia in neutropenic patients. The clinical features, outcomes, and antibiotic susceptibilities of VS bloodstream infections in children with hemato-oncological diseases are reported in this study.A retrospective chart review of pediatric patients (or =18 years) diagnosed with VS infections between January 1998 and December 2004 was conducted at the National Taiwan University Hospital.Among the 26 episodes noted in 25 pediatric patients, the incidence rate of VS bacteremia was found to be significantly higher in pediatric patients with acute myeloid leukemia compared with other hemato-oncological conditions. Most of the patients had profound neutropenia related to chemotherapy for a median of 5 days on the day of positive blood culture. Eight of the 25 patients had undergone stem cell transplantations. Streptococcus mitis was the most common bloodstream isolate and only 12 (44%) of the 27 isolated strains of VS were penicillin-susceptible. Empirical antibiotic treatments were not effective in half of the episodes, but did not affect overall mortality. Isolated bacteremia (63%) and pneumonia (22%) were the two leading clinical presentations. Complications were recognized more frequently in patients with pneumonia. Hypotension and mechanical ventilation each developed in 8 patients (31%). The overall mortality rate was 23%.Penicillin non-susceptible VS infection has emerged as a threat in children with hemato-oncological diseases, especially those with acute myeloid leukemia. S. mitis is the most common spp. of VS causing bacteremia in children and is associated with serious complications. The development of pneumonia resulted in clinical complications and higher mortality. Empirical antibiotic treatments with activity against the infecting strains did not reduce the overall mortality rate in this study.

To delineate the clinical manifestations in different age groups and to define the viral load in patients with Epstein-Barr virus-associated infectious mononucleosis (EBV-associated IM).We reviewed data on 69 children with EBV-associated IM from November 2001 to October 2005. Clinical features were evaluated among four age groups:3 years, 3 to 5 years, 6 to 9 years and 10 to 18 years. EBV viral load was measured by quantitative real-time polymerase chain reaction (PCR) in 13 patients with 15 specimens.Majority of the children were younger than 7 years of age (76.8%) and the male-to-female ratio was 1.6:1. The symptoms and signs included fever (91.3%), tonsillopharyngitis (88.4%), lymphadenopathy (78.3%) and hepatitis (75.4%). The younger age group had higher monocyte count, lower occurrence of hepatitis, and lower glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels than the older age group. The median (range) EBV viral load of peripheral blood mononuclear cells (PBMCs) and plasma in IM patients was 738 (0-7455) copies/mug DNA and 51 (0-957) copies/mL plasma, respectively. The PBMC detection rate was high in the early (within 10 days after onset) and late phase (10 days after onset) [90-100%]. The plasma detection rate in the early phase (66.7%) was higher than that in the late phase (40%).The younger age group of EBV-associated IM patients had higher monocyte count, lower occurrence of hepatitis, and lower GOT and GPT levels than the older age group. The PBMC detection rate was almost equally high in both the early and late phases, while the plasma detection rate was higher in the early phase. Quantitative real-time PCR of EBV DNA is useful for diagnosing and monitoring EBV-associated IM, especially in younger children.

Sixteen cases from the 1980-1981 Taiwan outbreak of hand, foot and mouth disease (HFMD) associated with central nervous system involvement were identified: nine had polio-like syndrome, four had encephalitis or encephalomyelitis, one had cerebellitis, and two had aseptic meningitis. They all had fever, five (31%) had documented myoclonic jerk, and 15 (93%) had HFMD. Their mean blood leukocyte count was 12,490/mL, and five (31%) had leukocytosis (> 15,000/mL); mean cerebrospinal fluid (CSF) leukocyte count was 156/mL, CSF protein was 57 mg/dL and CSF glucose was 57 mg/dL. Two patients with HFMD plus encephalitis died within 1 day of hospitalization, and one of them had acute cardiopulmonary failure mimicking myocarditis. Twenty years later, at least one male patient had sequelae of polio-like syndrome and was therefore exempted from military service. Clinical severity was comparable to the 1998 EV71 epidemic. [ J Formos Med Assoc 2007;106(2):173-176]

This study clinically and molecularly characterizes an adenovirus epidemic that broke out in Taiwan in April 2004. Clinical data on 325 children diagnosed with acute illness were collected between April 2004 and April 2005, and a diagnosis of adenovirus was confirmed by viral isolation. Polymerase chain reaction and restriction fragment length polymorphism were used to identify the adenovirus genotypes in 267 patients. There was a seasonal variation, with a peak incidence between November 2004 and January 2005 (p0.001). The median age was 52 months, range 1-210 months. Most cases (90.8%) were younger than 7 years old. Male-to-female ratio was 1.56:1. The most common clinical diagnosis was exudative tonsillitis (50.8%), followed by bronchitis/bronchiolitis (29.9%), conjunctivitis or pharyngoconjunctival fever (22.5%), and acute otitis media (16.3%). Adenovirus type 3 was found in 215 patients (80.5%). The other 52 patients had other genotypes: type 2 (10.1%), type 1 (6.0%), type 5 (1.9%), type 7 (0.7%), type 4 (0.4%), and type 6 (0.4%). Patients with type 3 were significantly older [age52 months, adjusted odds ratio (OR) 8.55, 95% confidence interval (CI) 1.84-40, p = 0.006), their family members had a higher incidence of illness (adjusted OR 8.77, 95% CI 1.55-50, p = 0.01), they coughed (adjusted OR 6.37, 95% CI 1.54-26.3, p = 0.01), and they had a higher C-reactive protein (CRP) level (2.87 mg/dL, adjusted OR 3.64, 95% CI 1.06-12.3, p = 0.04) than the 52 cases with other genotypes. In conclusion, this adenovirus outbreak, from late autumn to winter, was predominately caused by adenovirus type 3. Patients with this genotype were significantly older, had a higher incidence of cough and family transmission, and had higher CRP levels than those with other genotypes.

Objective.To investigate the potential reservoir and mode of transmission of pandrug-resistant (PDR) Acinetobacter baumannii in a 7-day-old neonate who developed PDR A. baumannii bacteremia that was presumed to be the iceberg of a potential outbreak.Design.Outbreak investigation based on a program of prospective hospital-wide surveillance for nosocomial infection.Setting.A 24-bed neonatal intensive care unit in a 2,200-bed major teaching hospital in Taiwan that provides care for critically ill neonates born in this hospital and those transferred from other hospitals.Interventions.Samples from 33 healthcare workers' hands and 40 samples from the environment were cultured. Surveillance cultures of anal swab specimens and sputum samples were performed for neonates on admission to the neonatal intensive care unit and every 2 weeks until discharge. The PDR A. baumannii isolates, defined as isolates resistant to all currently available systemic antimicrobials except polymyxin B, were analyzed by pulsed-field gel electrophoresis. Control measures consisted of implementing contact isolation, reinforcing hand hygiene adherence, cohorting of nurses, and environmental cleaning.Results.One culture of an environmental sample and no cultures of samples from healthcare workers' hands grew PDR A. baumannii. The positive culture result involved a sample obtained from a ventilation tube used by the index patient. During the following 2 months, active surveillance identified PDR A. baumannii in 8 additional neonates, and isolates from 7 had the same electrokaryotype. Of the 9 neonates colonized or infected with PDR A. baumannii, 1 died from an unrelated condition. Reinforcement of infection control measures resulted in 100% adherence to proper hand hygiene protocol. The outbreak was stopped without compromising patient care.Conclusions.In the absence of environmental contamination, transient hand carriage by personnel who cared for neonates colonized or infected with PDR A. baumannii was suspected to be the mode of transmission. Vigilance, prompt intervention and strict adherence to hand hygiene protocol were the key factors that led to the successful control of this outbreak. Active surveillance appears to be an effective measure to identify potential transmitters and reservoirs of PDR A. baumannii.

Pertussis is an acute respiratory tract illness resulting from Bordetella pertussis. Widespread use of pertussis vaccine over the past 50 years has decreased the incidence of pertussis. The incidence of pertussis in adolescents and adults has increased in many areas of the world. This study aimed to evaluate the etiologic role of B. pertussis in patients with prolonged cough in Taiwan.Patients with cough lasting for more than 1 week were recruited. Nasopharyngeal swabs were taken for culture of B. pertussis and detection of nucleic acid of B. pertussis by polymerase chain reaction. Serum samples were collected in a subset of patients for assay of immunoglobulin G and immunoglobulin A antibodies against pertussis toxin.In total, 111 patients were recruited. Thirty-three patients agreed to have their serum samples taken and tested. Eight patients had evidence of acute infection with B. pertussis; among them, 1 was diagnosed by polymerase chain reaction and 7 by serology. Older subjects were more likely to suffer from pertussis than younger subjects. The incidence of pertussis in patients with prolonged cough was 7.2%. However, the rate could have been as high as 21% in those with serum samples tested.We conclude that pertussis is a prevalent disease in Taiwan, especially in adolescents and adults.

This study investigated the clinical manifestations and outcomes of central nervous system (CNS) infection by enteroviruses. Cases with CNS involvement among all enterovirus-culture-positive cases from January 1995 to June 2003 were retrospectively reviewed. Among 1028 enterovirus-culture-positive cases, there were 333 cases involving the CNS. Of these, the ratio of male to female subjects was 1.78, and the mean (+/- standard deviation) age was 6.83 +/- 5.9 years; 21 were premature neonates, and 10 failed to thrive. Disease entities included 282 cases of aseptic meningitis (84.7%), 44 cases of encephalitis (13.2%), and 7 cases of encephalomyelitis/polio-like syndrome (2.1%). Of these cases, 97.9% (326/333) had fever with peak body temperature at 38.9 degrees C, 85% had headache and vomiting, 70% had meningeal signs, 64% had neck stiffness, 16.6% (55/333) had change of consciousness, 5.4% (18/333) had seizures and 5.2% (17/333) had myoclonic jerks. Mannitol was administered in 77.2% of patients (257/333), along with intravenous immunoglobulin in 6.6% (22/333). Twelve cases received ventilator support. One patient died of hand-foot-and-mouth disease, encephalitis plus cardiopulmonary failure, and 2 premature neonates died of hepatic failure, disseminated intravascular coagulation, sepsis-like syndrome and myocarditis. Eighteen had neurologic sequelae, including 7 with limb weakness, 5 with epilepsy, 2 with sixth cranial nerve palsy, 3 with cerebral palsy, 4 with psychomotor retardation, 2 with spasticity, and 1 with hearing loss. Factors associated with unfavorable outcomes (death or sequelae) included younger age (p=0.0003), higher peak white blood cell count (WBC) [p=0.0009] and skin rash (p=0.005). Younger age and higher peak WBC were poor prognostic factors of severe enterovirus CNS infection. Death was related to neonatal enterovirus infection and enterovirus 71 infection in young children.

In order to evaluate the clinical manifestations, management and outcome of childhood lung abscess, a retrospective chart review of 27 pediatric patients with International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9 CM) code of 503.1 (lung abscess) from August 1987 to August 2003 was conducted. Among the 27 patients (14 males and 13 females), 30% (8/27) were primary lung abscess and 70% (19/27) had underlying chronic diseases (secondary lung abscess). The predisposing factors of the primary group (n = 8) included 6 cases of respiratory tract infection, 1 with choking during swimming, and 1 with laceration wound. The underlying diseases in the secondary group (n = 19) included 10 cases of hematologic disorder (52%), 3 of congenital heart disease, 2 of central nervous system anomalies, and 1 each of hyperimmunoglobulin E syndrome, chronic lung disease, liver cirrhosis with fistula formation, and Swyer-James syndrome. Eleven patients (41%) underwent diagnostic tapping, including echo-guided aspiration (10 cases) and computed tomography-guided percutaneous needle aspiration (1 case). Positive yield rate from aspiration of lung abscess was 63.6% (7/11). Surgical intervention was performed in 8 (42%) of the secondary group and in 1 patient from the primary group. The pathogens were identified in 11 patients (41%): 5 with oral flora, 2 with Staphylococcus aureus plus other pathogens, 1 with S. aureus alone, 1 with Pseudomonas aeruginosa plus Proteus mirabilis, 1 with P. aeruginosa alone, and 1 with Aspergillus. The average duration of parenteral antibiotic use was 40 days. Five cases (18.5%) died due to poor control of the underlying diseases, and 4 of the patients (15%) had sequelae (2 with bronchiectasis and 2 with lung fibrosis). Seventy percent of lung abscess occurred in children with underlying medical conditions. Early percutaneous aspiration has an important role in identification of pathogens. Oral anaerobes and S. aureus are the core pathogens in primary lung abscess and gram-negative pathogens should also be considered in secondary lung abscess.

Purpose Disease caused by Bordetella pertussis is increasingly being identified among older children and adults in immunized populations, indicating a waning of the vaccine-induced immunity. These findings suggest the need for booster immunization of older children and adults. Modern acellular reduced-antigen-content vaccines have been developed, which can be given as a booster in individuals more than 4 years of age. This study was to assess the immunogenicity and reactogenicity of Boostrix™, GlaxoSmithKline Biologicals' reduced-antigen-content diphtheria-tetanus acellular pertussis (dTpa) vaccine, when administered as a booster in healthy subjects previously primed with DTP vaccine. Methods Healthy Taiwanese children and adolescents aged 6–8 years and 15–20 years, previously primed with DTP vaccine, were enrolled. All received one dose of Boostrix™. Two blood samples were taken from each of them, one before vaccination and one at 1 month after vaccination. Serum antibodies to diphtheria and tetanus toxoids and immunoglobulin G (IgG) antibodies against the pertussis components PT, FHA and PRN were measured by enzyme-linked immunosorbent assay (ELISA) technique. Adverse reactions following vaccination were recorded. Results A total of 180 subjects were recruited. The vaccine response rates to the pertussis antigens ranged between 89.0–100%. There were no serious adverse events reported during the study period. Conclusions The results of this study suggest that Boostrix™ may be safely and effectively administered as a booster dose to children previously primed with DTP vaccine.

A search of the computerized database at the National Taiwan University Hospital was made for cefotaxime-resistant and cefmetazole-susceptible isolates of Escherichia coli and Klebsiella pneumoniae (which may be extended-spectrum beta-lactamase-producing strains) in pediatric wards and intensive care units between 1999 and 2001. Fourteen infectious episodes attributed only to study bacteria were identified, including 7 episodes of bacteremia. Nine patients (64.3%) had underlying medical conditions: 3 were premature babies, 3 were immunodeficient, 2 had malignancy, and 2 had a congenital heart disease with active heart failure even after surgery. Among the 7 patients with bacteremias, 5 may be catheter-related; 6 were treated with carbapenems and 1 was treated with cefmetazole successfully, with or without the removal of the catheter. Before the acquisition of the infection, a history of stay in an intensive care unit within 4 weeks was noted in 10 cases (71.4%); a history of use of extended-spectrum cephalosporins within 4 weeks was also noted in 6 cases (42.9%). Cefmetazole, with or without an aminoglycoside, was clinically effective in 6 cases (42.8%). Except for 1 episode of pneumonia that ended in mortality, all of the infectious episodes were successfully treated. The mortality rate was 7.1%.