Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. METHODS: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. RESULTS: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. CONCLUSION: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Optimization of Mother-to-Child Hepatitis B Virus Prevention Program: Integration of Maternal Screening and Infant Post-vaccination Serologic Testing.

BACKGROUND: Evaluation of the impact on mother-to-child transmission (MTCT) of a HBV-prevention program that incorporates maternal antiviral prophylaxis is hindered by the limited availability of real-world data. METHODS: This study analyzed data on maternal HBV screening, neonatal immunization, and post-vaccination serologic testing (PVST) for HBsAg among at-risk infants born to HBV carrier mothers from the National Immunization Information System during 01/01/2008-31/12/2022. Through linkage with the National Health Insurance Database, information of maternal antiviral therapy was obtained. Multivariate logistic regression was performed to explore MTCT risk in relation to infant-mother characteristics and prevention strategies. RESULTS: Totally, 2,460,218 deliveries with maternal HBV status were screened. Between 2008 and 2022, the annual HBsAg and HBeAg seropositivity rates among native pregnant women aged 15-49 years decreased from 12.2% to 2.6% and from 2.7% to 0.4%, respectively (p for both trends < 0.0001). Among the 22,859 at-risk infants undergoing PVST, the MTCT rates differed between infants born to HBsAg-positive/HBeAg-negative and HBeAg-positive mothers (0.75% and 6.33%, respectively; p < 0.001). The MTCT rate was 1.72% (11/641) for infants born to HBeAg-positive mothers with antiviral prophylaxis. MTCT risk increased with maternal HBeAg-positivity (OR 9.29, 6.79-12.73) and decreased with maternal antiviral prophylaxis (OR 0.28, 0.16-0.49). For infants with maternal HBeAg-positivity, MTCT risk was associated with mothers born in the immunization era (OR 1.40, 1.17-1.67). CONCLUSIONS: MTCT was related to maternal HBeAg-positivity and effectively prevented by maternal prophylaxis in the immunized population. At-risk infants born to maternal vaccinated cohorts might possibly pose further risk.

Risk of Coronavirus Disease 2019 Messenger RNA Vaccination-Associated Myocarditis and Pericarditis - A Systematic Review of Population-Based Data.

Purpose: Early studies showed that the risks of mRNA vaccine-associated myocarditis and pericarditis are low but with substantial variation across studies. Study characteristics, ethnicity, vaccine types, dose intervals, and SARS-CoV-2 infection prevalence may influence the rates of myocarditis and pericarditis after mRNA vaccination in population-based studies. Methods: We comprehensively searched MEDLINE for relevant articles published before November 30, 2022. We also searched the websites of health authorities in several countries for unpublished surveillance data on myocarditis and pericarditis after mRNA vaccination. The outcome of interest was the incidence of myocarditis and pericarditis developed after mRNA vaccination for COVID-19. Results: A total of 17 studies form 10 countries were included for review. We noted that considerable heterogeneity in study characteristics, including surveillance method, case definition, and observation period, may partially be responsible for the widely varied reported rates. Studies from countries that adopted active surveillance reported higher rates than those using passive surveillance. Compared to BNT162b2 vaccine, mRNA-1273 may have a higher risk of myocarditis only in young men after the second dose. Our comparison of sex-, age-, vaccine type-, and dose-specific rates of myocarditis across countries did not support the hypothesis that individuals with recent SARS-CoV-2 infection and young Asian males were at higher risk. We also could not find sufficient evidence to conclude whether extending the between-dose interval could reduce myocarditis incidence following mRNA vaccination. Conclusion: Differences in the study characteristics must be fully considered when comparing the risks of mRNA vaccine-related myocarditis and pericarditis in different countries.

Acute reactions after a homologous primary COVID-19 vaccination series: Analysis of Taiwan V-Watch data.

INTRODUCTION: The ChAdOx1 nCoV-19 (ChAd), mRNA-1273 (m1273), MVC-COV1901 (MVC), and BNT162b2 (BNT) COVID-19 vaccines received authorization for emergency use in Taiwan beginning in February 2021. We investigated acute reactions to homologous primary COVID-19 vaccination series in adults aged ≥ 18 years. METHODS: In this prospective observational study based on smartphone data (Taiwan V-Watch), we calculated the frequencies of self-reported local and systemic acute reactions within 7 days of a COVID-19 vaccination, and the health effects up to 3 weeks after each dose. Those who reported adverse reactions after both doses were assessed by the McNemar test. RESULTS: During 22 March 2021-13 December 2021, 77,468 adults were enrolled; 59.0 % were female and 77.8 % were aged 18-49 years. For both doses of all four vaccines, the local and systemic reactions were minor in severity and highest on days 1 and 2 after vaccination, and declined markedly until day 7. For 65,367 participants who provided data after the first and second doses, systemic reactions were more frequent after dose 2 of the BNT and m1273 vaccines (McNemar tests: both p < 0.001), while local reactions were more frequent after dose 2 of the m1273 and MVC vaccines (both p < 0.001), compared with dose 1 of the homologous vaccine. Among the participants aged 18-49 years, the percentage who missed work on the day after vaccination was slightly higher among women (9.3 %) than among men (7.0 %). CONCLUSIONS: Acute reactogenicity and impact of work absenteeism for the four COVID vaccines in the V-Watch survey were mild and of short duration.

Risk of myocarditis and pericarditis following coronavirus disease 2019 messenger RNA Vaccination-A nationwide study.

BACKGROUND: An extended interval between the two primary doses may reduce the risk of myocarditis/pericarditis after COVID-19 mRNA vaccination. Taiwan has implemented a two-dose regimen with a 12-week interval for adolescents. Here we present nationwide data of myocarditis/pericarditis following COVID-19 vaccinations. METHODS: Data on adverse events of myocarditis/pericarditis were from the Taiwan Vaccine Adverse Events Reporting System between March 22, 2021, and February 9, 2022. The reporting rates according to sex, age, and vaccine type were calculated. We investigated the rates among young individuals under different two-dose intervals and among those who received two doses of different vaccines. RESULTS: Among 204 cases who met the case definition of myocarditis/pericarditis, 75 cases occurred after the first dose and 129 after the second. The rate of myocarditis/pericarditis after COVID-19 vaccination varied across sex and age groups and was highest after the second dose in males aged 12-17 years (126.79 cases per million vaccinees) for the BNT162b2 vaccine and in males aged 18-24 years (93.84 cases per million vaccinees) for the mRNA-1273 vaccine. The data did not suggest an association between longer between-dose interval and lower rate of myocarditis/pericarditis among males and females aged 18-24 or 25-29 years who received two doses of the BNT162b2 or mRNA-1273 vaccine. Rates of myocarditis/pericarditis in males and females aged 18-49 years after receiving ChAdOx1-S - mRNA-1273 vaccination was significantly higher than after ChAdOx1-S - ChAdOx1-S vaccination. CONCLUSIONS: Myocarditis and pericarditis are rare following mRNA vaccination, with higher risk occurring in young males after the second dose.

COVID-19 Severity and Neonatal BCG Vaccination among Young Population in Taiwan.

BACKGROUND: Data have not been reported to explore the relation between COVID-19 severity and BCG vaccination status at the individual patient level. METHODS: Taiwan has a nationwide neonatal BCG vaccination program that was launched in 1965. The Taiwan Centers for Disease Control established a web-based National Immunization Information System (NISS) in 2003 and included all citizens' BCG vaccination records in NISS for those born after 1985. We identified COVID-19 Taiwanese patients born after 1985 between 21 January and 19 March 2021. Study participants were further classified into ages 4-24 years (birth year 1996-2016) and 25-33 years (birth year 1986-1995). We described their clinical syndrome defined by the World Health Organization and examined the relation between the COVID-19 severity and BCG vaccination status. RESULTS: In the 4-24 age group, among 138 BCG vaccinated individuals, 80.4% were asymptomatic or had mild disease, while 17.4% had moderate disease, 1.5% had severe disease, and 0.7% had acute respiratory distress syndrome but none of them died. In contrast, all 6 BCG unvaccinated individuals in this age group experienced mild illness. In the 25-33 age group, moderate disease occurred in 14.2% and severe disease occurred in 0.9% of the 106 patients without neonatal BCG vaccination records, as compared to 19.2% had moderate disease and none had severe or critical disease of the 78 patients with neonatal BCG vaccination records. CONCLUSIONS: Our finding indicated that BCG immunization might not relate to COVID-19 severity in the young population.

Application of the screening and indirect cohort methods to evaluate the effectiveness of pneumococcal vaccination program in adults 75 years and older in Taiwan.

BACKGROUND: The Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children. METHODS: The incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods. RESULTS: The incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008-June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67-0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5-44.7%), 33.9% (95% CI: 25.2-41.5%) and 43.4% (95% CI: 34.4-51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5-55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2-85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008-June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2-72.3%). CONCLUSIONS: PPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children.

The Impact of Universal Infant Hepatitis B Immunization on Reducing the Hepatitis B Carrier Rate in Pregnant Women.

BACKGROUND: The hepatitis B virus (HBV) status of pregnant women affects HBV vaccine failure in their offspring. This study is aimed to investigate the impact of the universal infant HBV vaccination program on the long-term hepatitis B surface antigen (HBsAg) rate in pregnant women. METHODS: Using the National Immunization Information System, we examined a 32-year period of cross-sectional data on a maternal HBsAg and hepatitis B e antigen (HBeAg) screening program launched in July 1984. An age-period-cohort model analysis of 940 180 pregnant women screened for July 1996-June 1997 and the years 2001, 2006, 2011, and 2016 was applied. RESULTS: The annual HBsAg- and HBeAg-seropositive rates decreased from 13.4% and 6.4%, respectively, for the period 1984-1985 to 5.9% and 1.0% in 2016 (P for both trends < .0001). Pregnant women with birth years after July 1986 (the HBV vaccination cohort) had the lowest relative risk (0.27 [95% confidence interval, .26-.28]) of HBsAg positivity compared with birth years before June 1984. CONCLUSIONS: The birth cohort effect in relation to the universal infant HBV immunization program has effectively reduced the HBV carrier rate in pregnant women and the burden of perinatal HBV infection on the next generation.

Neutrophil-lymphocyte ratio and CEA level as prognostic and predictive factors in colorectal cancer: A systematic review and meta-analysis.

INTRODUCTION: There is a growing body of evidence showing the functional relationship between inflammation index like netrophil.lymphocyte ratio. (NLR) and colorectal cancer. (CRC) in both experimental and clinical situations. The serum carcinoembryonic antigen. (CEA) level is the most widely used marker and associate with poor prognosis in most studies. For these factors to be clinically useful, they should be routinely available, well standardized, and validated in different patient cohorts. AIMS: There is a growing body of evidence showing the functional relationship between inflammation index like netrophil-lymphocyte ratio. (NLR) and colorectal cancer. (CRC) in both experimental and clinical situations. The serum carcinoembryonic antigen. (CEA) level is the most widely used marker and associate with poor prognosis in most studies. For these factors to be clinically useful, they should be routinely available, well standardized, and validated in different patient cohorts. MATERIALS AND METHODS: We systemically searched PubMed, Embase, and SciVerse Scopus databases, and performed a meta.analysis by Review Manager 5.2 software. (The Cochrane Collaboration, Software Update, Oxford). Two reviewers selected studies, assessed risk of bias, and extracted data independently. Newcastle.Ottawa Scale was applied to assess the quality of included studies. RESULTS: Fifteen studies involving 7741 patients with CRC were analyzed. Patients with an NLR < 5 before treatment were significantly more likely to have 5-year overall survival (odds ratio [OR] = 2.03; 95% confidence interval [CI] = 1.56-2.63) and 5-year disease-free survival (OR = 1.67; 95% CI = 1.19-2.35). Pretreatment CEA level < 5 were significantly associated with complete tumor response and tumor downstaging after neoadjuvant treatment. The result also showed that patients with NLR > 5 were expected to have a larger tumor, poorer tumor differentiation, and higher CEA level. CONCLUSION: NLR and CEA are valuable tools for the prediction of prognosis in CRC and adjusting the treatment strategy.

Effectiveness of Pneumococcal Conjugate Vaccines of Different Valences Against Invasive Pneumococcal Disease Among Children in Taiwan: A Nationwide Study.

BACKGROUND: For the scarcity of data, we investigated the vaccine effectiveness (VE) of the combined use of pneumococcal conjugate vaccines (PCVs) of different valences against invasive pneumococcal disease (IPD) in children. METHODS: We conducted a matched case-control study using the national IPD surveillance database and the national vaccination registry. Four age-matched, gender-matched and neighborhood-matched controls were identified for each incident IPD case ≦5 years with disease onsets between October 2007 and December 2013. Conditional logistic regression was used to assess VE against all serotype and serotype 19A IPD. RESULTS: In 523 cases (median age: 28.5 months; range: 2.0-69.4 months) and 2086 controls (28.7; 2.2-70.1), a similar VE against all-serotype IPD was found between PCV13 (76%; 61-85%) and combined 7-valent PCV (PCV7)/10-valent PCV (PCV10) plus PCV13 (78%; 56-89%). The VE for PCV7/PCV10 was slightly lower (48%; 32-60%). Regarding serotype 19A, a significantly reduced risk was observed for both PCV13 (82%; 63-91%) and combined PCV7/PCV10 plus PCV13 (87%; 61-96%). PCV7/PCV10 had only a borderline protective association (31%; 4-51%). For children receiving PCV13 alone, VE against all-serotype IPD did not differ between starting the dosing at ≥2 (78%; 56-89%) or <2 (74%; 51-87%) years of age. VE was 81% (69-88%) within 6 months of the last dose of PCV and 19% (95% CI: -21 to 45%) after 2 years. CONCLUSIONS: PCVs are effective against IPD during immunization with either the same or with a mixed series, but protection might be differential over time.

Estimating influenza vaccine effectiveness using routine surveillance data among children aged 6-59 months for five consecutive influenza seasons.

OBJECTIVES: We aimed to estimate the pooled vaccine effectiveness (VE) in children over five winters through data linkage of two existing surveillance systems. METHODS: Five test-negative case-control studies were conducted from November to February during the 2004/2005 to 2008/2009 seasons. Sentinel physicians from the Viral Surveillance Network enrolled children aged 6-59 months with influenza-like illness to collect throat swabs. Through linking with a nationwide vaccination registry, we measured the VE with a logistic regression model adjusting for age, gender, and week of symptom onset. Both fixed-effects and random-effects models were used in the meta-analysis. RESULTS: Four thousand four hundred and ninety-four subjects were included. The proportion of influenza test-positive subjects across the five seasons was 11.5% (132/1151), 7.2% (41/572), 23.9% (189/791), 6.6% (75/1135), and 11.2% (95/845), respectively. The pooled VE was 62% (95% confidence interval (CI) 48-83%) in both meta-analysis models. By age category, VE was 51% (95% CI 23-68%) for those aged 6-23 months and 75% (95% CI 60-84%) for those aged 24-59 months. CONCLUSIONS: Influenza vaccination provided measurable protection against laboratory-confirmed influenza among children aged 6-59 months despite variations in the vaccine match during the 2004/2005 to 2008/2009 influenza seasons in Taiwan.

Effect of age on the incidence of acute hepatitis B after 25 years of a universal newborn hepatitis B immunization program in Taiwan.

BACKGROUND: Raising concerns about the waning immunity of cohorts receiving hepatitis B virus (HBV) vaccination in infancy persuaded us to identify the changing incidence of acute hepatitis B (AHB) in children and young adults. METHODS: Data on AHB surveillance through the National Notifiable Disease Surveillance System from July 2001 to June 2009 were collected and described. Cases were divided into 2 cohorts according to their birth year: before or after the universal newborn HBV vaccination program. Age-specific incidence was compared for the 2 birth cohorts with diagnosis at age 15-24 years. RESULTS: In total, 2226 patients with AHB were identified. AHB rates varied by age; the highest rates occurred among unvaccinated individuals aged 25-39 years (2.33/100 000). Due to breakthrough HBV infection from mother-to-infant transmission, vaccinated infants (0.78/100 000) had higher rates than those aged 1-14 years (0.04/100 000), who had the lowest rates. The incidence in vaccinated birth cohorts was significantly lower than in unvaccinated birth cohorts among patients 15-24 years old, with an adjusted-relative risk of 0.42. CONCLUSIONS: Implementation of universal-at-birth HBV immunization programs has effectively reduced the occurrence of AHB among adolescents and young adults in Taiwan for >25 years, making infants and the 25-39-year-old cohort additional targets for preventing AHB.

An examination of cancer-related fatigue through proposed diagnostic criteria in a sample of cancer patients in Taiwan.

BACKGROUND: Fatigue among cancer patients has often been reported in the literature; however, great variations have been documented, ranging from 15% to 90%, probably due to the lack of a widely accepted definition and established diagnostic criteria for cancer-related fatigue. The objective of this study was to evaluate the proposed International Statistical Classification of Diseases and Related Health Problems (10th revision) (ICD-10) criteria in a sample of cancer patients from a medical center and a regional teaching hospital in northern Taiwan. More accurate prevalence estimates of CRF may result in improved diagnoses and management of one of the most common symptoms associated with cancer and its treatment. METHODS: Since self-reporting from patients is the most effective and efficient method to measure fatigue, the ICD-10 criteria for fatigue were used. The ICD-10 criteria questionnaire was translated into Chinese and was approved by experts. Patients were recruited from outpatient palliative and oncology clinics and from palliative and oncology inpatient units. RESULTS: Of the 265 cancer patients that were interviewed between 21 October 2008 and 28 October 2009, 228 (86%) reported having at least 2 weeks of fatigue in the past month, and further evaluation with the ICD-10 criteria showed that 132 (49.8%) had cancer-related fatigue. Internal consistency was very good, which was indicated by a Cronbach alpha of 0.843. CONCLUSION: The prevalence of diagnosable CRF in the patients in this sample, of whom most were under palliative treatment, was 49.8%, which was probably somewhat lower than in some of the previous reports that have used less-strict criteria. In addition, among the various criteria of the proposed diagnostic criteria, the most frequently reported symptoms in our sample populations were regarding sleep disturbance and physical factors. Although they will require further replication in other samples, these formal diagnostic criteria can serve as a step toward a common language and a better understanding of the severity range of CRF.

Risk of ovarian cancer in women with pelvic inflammatory disease: a population-based study.

BACKGROUND: Ovarian cancer is commonly fatal and incidence has persistently risen in Taiwan over the past 20 years. Prevention strategies, however, are limited. Pelvic inflammatory disease (PID) has been suggested to increase the risk of developing ovarian cancer, but the results of studies have been inconsistent. Therefore, we investigated whether PID increases the risk of developing ovarian cancer in a large, nationwide cohort. METHODS: From the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan, we obtained data for women aged 13-65 years for whom a diagnosis of PID, confirmed by multiple episodes, had been recorded between Jan 1, 2004, and Dec 31, 2005. We also obtained data for two controls per patient, matched for age and the year of first entry into the LHID2005. All patients were followed up from the date of entry in the LHID2005 until they developed ovarian cancer or to the end of 2006, whichever was earlier. We used Cox's regression models to assess the risk of developing ovarian cancer, with adjustment for age, comorbid disorders, and socioeconomic characteristics. FINDINGS: We identified 67,936 women with PID and 135,872 controls. Among these 90 had developed ovarian cancer during the 3-year follow-up period (42 patients with PID and 48 controls, incidence 2·78 and 1·44 per 10,000 person-years, respectively). The adjusted hazard ratio for ovarian cancer in patients with PID was 1·92 (95% CI 1·27-2·92) compared with controls, which rose to 2·46 (1·48-4·09) in women who had had at least five episodes of PID. The adjusted hazard ratio was slightly higher for women aged 35 years or younger with PID than in older women with PID (2·23, 1·02-4·79 vs 1·82, 1·10-3·04). INTERPRETATION: We found an association between PID and ovarian cancer. PID might, therefore, be a useful marker for ovarian cancer, and early treatment could help to improve prognosis. Whether pelvic inflammation itself accelerates the growth of ovarian cancers or affects cancer-cell differentiation in ways that adversely alter prognosis needs to be investigated. FUNDING: None.

Low seroprevalence of parvovirus B19 in Taiwanese children and young adults.

BACKGROUND: This study aimed to evaluate the prevalence of parvovirus B19 antibodies in children and young adults aged=30 years old in Taiwan. METHODS: Stored serum samples from healthy volunteers aged 1-29 years in Taipei were randomly selected and tested for antiparvovirus B19 immunoglobulin G by enzyme immunoassay. RESULTS: A total of 277 serum samples were tested. The overall seroprevalence of parvovirus B19 in Taiwanese children and young adults was 23.1% (64/277) in 2004. The positive rate increased slightly with age; it ranged from 15.0% in those aged 1-4 years to 30.8% in those aged 25-29 years (trend test, p=0.01). The age-adjusted anti-B19 immunoglobulin G seropositive rate was slightly higher in males (27.8%) than in females (18.8%; adjusted odds ratio: 0.56; 95% confidence interval: 0.32-0.99). CONCLUSION: Most children and young adults in Taipei City are not immune to parvovirus B19, suggesting that no parvovirus B19 epidemic has occurred in the last few decades.

Low seroprotection against preseasonal influenza local strains in children might predict the upcoming epidemic influenza strains.

BACKGROUND. Our objective was to determine the serological signals that indicated the possible dominant circulating influenza virus subtypes for the coming influenza seasons. METHODS. Healthy children 6 months through 5 years of age, adults 18-60 years of age, and elderly adults >60 years of age were recruited to receive seasonal trivalent inactivated influenza vaccinations from October through December during the 2006-2007 and 2008-2009 seasons. Paired serum samples were collected at baseline and at 3 weeks after vaccination. Using a hemagglutination inhibition (HAI) assay, we measured antibody responses to local influenza strains circulating early in October, before each winter influenza season. RESULTS. A total of 301 subjects were tested for antibody to local strains (80, 120, and 101 subjects in the 2006-2007, 2007-2008, and 2008-2009 seasons, respectively). The dominant winter influenza strains in Taiwan were B/Malaysia/2506/2004-like in the 2006-2007 season, A/Brisbane/59/2007-like virus (H1N1) in the 2007-2008 season, and A/Brisbane/59/2007-like virus (H1N1) in the 2008-2009 season. The group with the lowest number of subjects with an HAI titer of 40 at baseline was children with antibody against the B/Taiwan/0050/2006 in the 2006-2007 season, A/Taiwan/785/2006 (H1N1) in 2007-2008 season, and A/Taiwan/951/2007 (H1N1) in 2008-2009 season. The emergence of these viruses correlated well with the circulating influenza subtype in the following winter peak seasons. CONCLUSIONS. Low seroprotection rate among children against a specific locally circulating influenza strain might predict the dominantly circulating subtype of influenza virus in the coming winter season. A year-end preseasonal serological survey of children could provide valuable information about the possible circulating strain and tailor the disease-control strategy accordingly.

Clinical course of de novo hepatitis B infection after pediatric liver transplantation.

The characteristics of hepatitis B virus (HBV) in vaccinated children who acquire de novo HBV infections after orthotopic liver transplantation (OLT) remain largely unknown. The aim of this study was to explore HBV mutants in pediatric OLT recipients with de novo HBV infections. In all, 50 recipients underwent OLT between December 1997 and October 2005, and they were regularly checked for HBV serum markers from November 2005 to April 2009. Before OLT, all were hepatitis B surface antigen (HBsAg)-negative and under the coverage of the universal infant HBV vaccination program. Those who became HBsAg-positive after OLT were diagnosed with de novo HBV infection. HBV viral loads and full-length genome sequencing were determined when the diagnosis of de novo HBV infection was established. Nine patients (9/50, 18%) acquired de novo HBV infections after OLT. None had graft loss or fulminant hepatitis. Five cleared HBsAg, and 4 of the 5 even recovered with antibody to hepatitis B surface antigen (anti-HBs) formation. The other 4 were persistently HBsAg-positive. Mutations in the major S gene (681 base pairs) were discovered in 8 (88.9%) of the de novo HBV-infected children. Six of them harbored mutations within the "a" determinant region (codons 124-147), whereas the other 2 had mutations outside this region. These 2 cleared HBsAg and recovered with anti-HBs formation. HBV DNA levels were not different between those who cleared HBsAg and those who did not. In conclusion, surface mutants are frequent among pediatric liver transplant recipients with de novo HBV infections, but their clinical relevance requires further study.