Longitudinal neutralizing antibody responses after SARS-CoV-2 infection: A convalescent cohort study in Taiwan.

BACKGROUND: Understanding the neutralizing antibody (NAb) titer against COVID-19 over time is important to provide information for vaccine implementation. The longitudinal NAb titer over one year after SARS-CoV-2 infection is still unclear. The purposes of this study are to evaluate the duration of the neutralizing NAb titers in COVID-19 convalescents and factors associated with the titer positive duration. METHODS: A cohort study followed COVID-19 individuals diagnosed between 2020 and 2021 May 15th from the COVID-19 database from the Taiwan Centers for Disease Control. We analyzed NAb titers from convalescent SARS-CoV-2 individuals. We used generalized estimating equations (GEE) and a Cox regression model to summarize the factors associated with NAb titers against COVID-19 decaying in the vaccine-free population. RESULTS: A total of 203 convalescent subjects with 297 analytic samples were followed for a period of up to 588 days. Our study suggests that convalescent COVID-19 in individuals after more than a year and four months pertains to only 25% of positive titers. The GEE model indicates that longer follow-up duration was associated with a significantly lower NAb titer. The Cox regression model indicated the disease severity with advanced condition was associated with maintaining NAb titers (adjusted hazard ratio: 2.01, 95% CI: 1.11-3.63) and that smoking was also associated with higher risk of negative NAb titers (adjusted hazard ratio: 0.55, 95% CI: 0.33-0.92). CONCLUSIONS: Neutralizing antibody titers diminished after more than a year. The antibody titer response against SARS-CoV-2 in naturally convalescent individuals provides a reference for vaccinations.

Towards the first 90: impact of the national HIV self-test program on case finding and factors associated with linkage to confirmatory diagnosis in Taiwan.

INTRODUCTION: Being aware of one's HIV-positive status can help reduce unprotected sex and promote early treatment seeking. Therefore, HIV self-test (HIVST) programs may help control the HIV epidemic by case finding. The aims of this study were to determine the effect of HIVST programs on HIV case finding, time to confirmatory diagnosis and factors associated with linkage to confirmatory diagnosis in Taiwan. METHODS: The Centers for Disease Control in Taiwan initiated HIVST programs and imported 78,000 self-test kits in 2017 and 2019. Clients paid 7 US dollars for a self-test kit at facilities, vending machines or online. The programs set up an HIVST logistics management system; each kit had a unique barcode for monitoring the programs because purchases were anonymous. When clients provided their test results with photo barcodes online or at HIV/AIDS-designated hospitals, they received full monetary reimbursement. We conducted a quasi-experimental interrupted time-series (ITS) analysis that covered a period of 60 months from 2015 to 2019. We enrolled a retrospective cohort of reported HIV cases with initial positive results from HIVST programs between March 2017 and July 2020. RESULTS: The ITS analysis included data from 10,976 reported HIV cases from 2015 to 2019. The HIVST-positive cohort included 386 reported HIV cases, of whom 99.7% were males and 97% were men who have sex with men (MSM); the median age was 28 years. The ITS analysis showed a positive slope change in the number of reported HIV cases immediately in the beginning implementation month (coefficient: 51.09 in 2017 and 3.62 in 2019), but there was a significant decrease over time. It was a negative slope change by 9.52 cases per month in 2017 and 5.56 cases per month in 2019. In the HIVST-positive cohort, three of five individuals linked to HIV confirmatory diagnosis within 1 month after a positive self-test result, and an early linkage to confirmatory diagnosis was associated with HIVST disclosure (adjusted OR = 6.5; 95% CI: 3.9-10.6). CONCLUSIONS: HIVST programs were associated with an increase in HIV case finding. Our findings suggest that countries with a high incidence of HIV among MSM populations should offer multichannel HIVST services.

COVID-19 vaccinations are associated with reduced fatality rates: Evidence from cross-country quasi-experiments.

BACKGROUND: Scientists have demonstrated the efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 in randomized controlled trials. However, the extent to which reductions in COVID-19 case fatality ratio (CFR) are attributable to mass vaccination in the real world remains unclear. This study evaluated the association of COVID-19 vaccine coverage with CFR on a global scale. METHODS: The sample was a longitudinal data set of 90 countries over 25 weeks, from the first week of November 2020 to the third week of April 2021. CFR was measured in deaths per 100 COVID-19 confirmed cases; vaccine coverage was defined as the number of people who received at least one vaccine dose per 10 people in the total population. Data were retrieved from open-access databases, including Our World in Data and the Oxford COVID-19 Government Response Tracker. A country-level random effects model was used; a comprehensive set of variables for country characteristics and nonpharmaceutical interventions were included. RESULTS: A 10% increase in vaccine coverage was associated with a 7.6% reduction in the CFR (95% confidence interval (CI = -12.6 to -2.7%, P = 0.002). This association was stronger in countries with more effective governments (-8.3%; 95% CI = -13.6 to -3.1%, P = 0.002) and higher transport infrastructure quality (-8.1%; 95% CI = -13.3 to -2.9%, P = 0.002). Moreover, the vaccine coverage was associated with a reduced CFR in a dose-dependent manner. When vaccine coverage achieved 0.8 to 1.6, 1.6 to 3.2 and ≥3.2 per 10 people, the CFR reduced by 12.7% (95 CI = -21.8 to -3.6%, P = 0.006), 21.2% (95 CI = -33.9 to -8.5%, P = 0.001) and 31.3% (95 CI = -51.5 to -11.0%, P = 0.002), respectively as compared with no vaccination. CONCLUSIONS: Our results provide supporting evidence that vaccination is critical to preventing deaths among infected people. Vaccination programmes have yielded significant health benefits in certain countries. However, globally, a large gap remains between observed and achievable fatality reductions. Continuous improvement in vaccine coverage will be critical to transforming efficacious vaccines into desired health outcomes.

Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer.

BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. METHODS: We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. RESULTS: Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P < .001 and 1986-1992 vs 1984-1986; P < .002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC. CONCLUSIONS: Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer.

Changes in HIV incidence among people who inject drugs in Taiwan following introduction of a harm reduction program: a study of two cohorts.

BACKGROUND: Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID. METHODS AND FINDINGS: The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6-12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06-0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates. CONCLUSIONS: Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID. Please see later in the article for the Editors' Summary.

Incomplete hepatitis B immunization, maternal carrier status, and increased risk of liver diseases: a 20-year cohort study of 3.8 million vaccinees.

UNLABELLED: Hepatitis B immunization has been documented to prevent fulminant hepatic failure (FHF) and hepatocellular carcinoma (HCC) by historical comparison studies in Taiwan. This study aimed to assess long-term risks and predictors of various liver diseases associated with incomplete immunization in 3.8 million vaccinees. Profiles of the National Hepatitis B Immunization Registry, National Cancer Registry, and National Death Certification Registry were linked to ascertain newly diagnosed cases of HCC and deaths from FHF and chronic liver diseases (CLDs) from infancy to early adulthood of 3,836,988 newborn vaccinees. Cox's proportional hazards models were used to estimate hazard ratios (HRs) for various risk predictors. There were 49 newly developed cases of HCC, 73 deaths from FHF, and 74 deaths from CLDs during the follow-up of 41,854,715 person-years. There were striking differences between unvaccinated and vaccinated newborns after the launch of a national immunization program for HCC incidence (0.293 vs. 0.117 per 100,000 person-years), FHF mortality (0.733 vs. 0.174 per 100,000 person-years), and CLD mortality (2.206 vs. 0.177 per 100,000 person-years). Among vaccinees, incomplete immunization was the most important risk predictor of HCC, FHF, and CLDs, showing an HR (95% confidence interval, P value) of 2.52 (1.25-5.05; P = 0.0094), 4.97 (3.05-8.11; P < 0.0001), and 6.27 (3.62-10.84; P < 0.0001), respectively, after adjustment for maternal hepatitis B serostatus. CONCLUSION: Hepatitis B immunization can significantly prevent the long-term risk of HCC, FHF, and CLDs from infancy to early adulthood. Incomplete immunization with hepatitis B immunoglobulin or vaccines was the most important risk predictor of the liver disease among vaccinees.

Trends in tuberculosis in Taiwan, 2002-2008.

BACKGROUND/PURPOSE: Tuberculosis (TB) remains an important infectious disease in Taiwan. To control TB effectively, the Taiwan Centers for Disease Control implemented the National Tuberculosis Program (NTP) in 2006, modeled on the World Health Organization global TB control program. The goal of the program was to reduce the number of TB cases by half within a decade. This study was designed to describe the epidemiology of TB in Taiwan, and to evaluate the preliminary effectiveness of the NTP. METHODS: We conducted a retrospective study of data from the National Tuberculosis Registry System collected between 2002 and 2008. Demographics, geographic distribution of disease, and change in rates of TB incidence and mortality were analyzed. RESULTS: From 2002 to 2008, new TB cases declined from 16,758 to 14,265, and incidence decreased from 75 per 100,000 population to 62 per 100,000 population. More than 50% of new cases occurred among elderly adults. Over the study period, TB mortality decreased from 5.7 per 100,000 population to 3.3 per 100,000 population, with over half of TB deaths occurring among patients aged ≥ 65 years. Since the NTP was implemented, from 2005 to 2008, TB incidence and mortality declined by 14% and 23%, respectively. CONCLUSION: TB-associated incidence and mortality decreased over the course of the study. Nevertheless, there continue to be high-incidence areas that show the opposite trend; these areas should strive to improve case management and consultation. In the most populous districts, rigorous surveillance is necessary to track incidence and mortality rate fluctuations.

Hepatitis B virus infection and risk of intrahepatic cholangiocarcinoma and non-Hodgkin lymphoma: a cohort study of parous women in Taiwan.

UNLABELLED: Few studies have evaluated the risk of cancers other than hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. This study aimed to estimate incidence rates of intrahepatic cholangiocarcinoma (ICC) and non-Hodgkin lymphoma (NHL) and its major subtypes in a nationwide cohort of parous women and to assess their associations with chronic HBV infection. We conducted a cohort study including 1,782,401 pregnant Taiwanese women whose HBV serostatus was obtained from the National Hepatitis B Vaccination Registry. Newly diagnosed ICCs and NHLs were ascertained through data linkage with the National Cancer Registry. Risks of ICC and NHL were assessed using Cox proportional hazards regression models. After a mean of 6.91 years of follow-up, there were 18 cases of ICC and 192 cases of NHL, including 99 cases of diffuse large B-cell lymphoma (DLBCL). Incidence rates of ICC were 0.09 and 0.43 per 100,000 person-years, respectively, among women who were hepatitis B surface antigen (HBsAg)-seronegative and HBsAg-seropositive, showing an age-adjusted hazard ratio (HR(adj) ) (95% confidence interval [CI]) of 4.80 (1.88-12.20). The incidence rates of NHL overall for HBsAg-seronegative and HBsAg-seropositive women were 1.23 and 3.18 per 100,000 person-years, respectively, with an HR(adj) (95% CI) of 2.63 (1.95-3.54). Among NHL subtypes, HBsAg-seropositive women had an increased risk of DLBCL compared with those who were HBsAg-seronegative (incidence rates: 1.81 and 0.60 per 100,000 person-years, respectively; HR(adj) [95% CI]: 3.09 [2.06-4.64]). The significantly increased risk was not observed for other specific subtypes of NHL. CONCLUSIONS: Chronic HBV infection was associated with an increased risk of ICC and DLBCL in women. Our data suggested a possible etiological role of HBV in the development of ICC and specific subtypes of NHL.

Mortality among a cohort of drug users after their release from prison: an evaluation of the effectiveness of a harm reduction program in Taiwan.

AIMS: To determine the effect of methadone maintenance therapy (MMT) on mortality among injection drug users. DESIGN: A cohort of prisoners with a history of injecting opiates who were followed after their release from prison in July 2007. Mortality between July 2007 and December 2008 was determined by linking the National Death Registry with the Methadone Maintenance Treatment (MMT) database. SETTING: Taiwan. PARTICIPANTS: A total of 4357 amnestied prisoners with a history of opiate injection. MEASUREMENTS: The total mortality rates (MR) among the cohort were calculated based on their person-time contribution to methadone attendance and re-incarceration during follow-up. We used survival methods with MMT and re-incarceration as time-varying covariates adjusted for length of follow-up in the community. RESULTS: A total of 142 deaths occurred: 13 in the 1st week after release [MR = 13.7/100 person-years (pyrs)], which was greater than that in the next 4 weeks [MR = 3.2/100 pyrs, relative rate (RR) = 4.3, P < 0.001]. Overall, 1982 (46%) subjects enrolled in MMT; however, 1282 of them discontinued MMT after enrolling. FINDINGS: The mortality among those who continued in MMT attendance was lower (MR = 0.24/100 pyrs) than those who never enrolled in MMT (MR = 2.6/100 pyrs) or those who enrolled but dropped out of MMT (MR = 7.0/100 pyrs) after adjusting for age, gender and human immunodeficiency virus status at amnesty (RR = 0.07). CONCLUSIONS: In ex-prisoners in Taiwan with a history of opiate injecting, enrollment and continued participation in methadone maintenance treatment is associated with substantially lower mortality.

Social and economic impact of school closure resulting from pandemic influenza A/H1N1.

OBJECTIVES: On May 23, 2009, a school was closed for one week plus mass chemoprophylaxis to contain the pandemic after a kindergartener tested positive for pandemic influenza A/H1N1. We evaluated the impact of school closure on the students, families, and the school. METHODS: Households were surveyed using a questionnaire to obtain information on adherence to, socio-economic impact by and inconveniences of school closure. The school principal was interviewed to assess the impact on the staff. Compliance and adverse events of chemoprophylaxis were assessed. RESULTS: Of the 232 (14%) households surveyed, 29 (13%) went to public places or gatherings at least once during the closure. Sixty-one (27%) of 229 respondents reported workplace absenteeism, and 42 (18%) of 231 respondents had wage loss. In total, 194 working days lost and 6433 US dollars wage lost were noted. The school put in 6573 h of manpower during the period. For chemoprophylaxis, 6 (6%) kindergartners missed at least one dose; and 6 (6%) reported adverse events, but none sought medical care. Overall, 169 (73%) families were at least moderately supportive of school closure. CONCLUSIONS: With assistance from the school, short-term school closure was supported by the majority of families despite economic inconvenience to the households.

Efficient simulation of the spatial transmission dynamics of influenza.

Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies over-estimated the within-country rate of spatial spread of pandemic influenza. As large spatially resolved data sets are constructed, the need for efficient simulation code with which to investigate the spatial patterns of the pandemic becomes clear. Here, we present a significant improvement to the efficiency of an individual-based stochastic disease simulation framework commonly used in multiple previous studies. We quantify the efficiency of the revised algorithm and present an alternative parameterization of the model in terms of the basic reproductive number. We apply the model to the population of Taiwan and demonstrate how the location of the initial seed can influence spatial incidence profiles and the overall spread of the epidemic. Differences in incidence are driven by the relative connectivity of alternate seed locations. The ability to perform efficient simulation allows us to run a batch of simulations and take account of their average in real time. The averaged data are stable and can be used to differentiate spreading patterns that are not readily seen by only conducting a few runs.

Design of a robust infrastructure to monitor the safety of the pandemic A(H1N1) 2009 vaccination program in Taiwan.

On November 1, 2009, Taiwan began a nationwide pandemic A(H1N1) 2009 vaccine ("H1N1 vaccine") program to control the influenza pandemic. Timely assessment of immunization safety during this mass vaccination campaign was a public health priority. Therefore, the government developed a national postlicensure safety surveillance strategy to identify and evaluate new, unexpected, or prioritized adverse events in recipients of H1N1 vaccine in near real-time. We describe the design and methodology of this new safety assessment infrastructure, address challenges encountered, and its potential future use for routine vaccine pharmacovigilance in Taiwan.

Mortality after chronic hepatitis B virus infection: a linkage study involving 2 million parous women from Taiwan.

BACKGROUND: Few studies have evaluated survival rates among women who have chronic hepatitis B virus infection. We investigated the overall and disease-specific mortality rates in a nationwide cohort of women after they were screened for hepatitis B surface antigen (HBsAg) during pregnancy. METHODS: HBsAg prenatal screening data were available for 2,087,994 women in Taiwan between 1 January 1986 and 31 March 2000 in the National Hepatitis B Vaccination Registry. Their vital status and cause of death were ascertained by computerized linkage with the National Death Certification Registry. Cox proportional hazards models were used to estimate the association between HBsAg status and specific causes of death. RESULTS: Overall, 14,524 deaths were identified after a mean of 11.43 years of follow-up. The age-adjusted hazard ratio for mortality among HBsAg carriers compared with noncarriers was 1.24 (95% confidence interval [CI], 1.19-1.30), 6.59 (95% CI, 5.70-7.61), and 1.09 (95% CI, 1.04-1.14) for all-cause, liver-specific, and non-liver-related deaths, respectively. In addition to liver-specific causes, a significantly increased risk of mortality from non-Hodgkin lymphoma (P < .001) and gallbladder and extrahepatic bile duct cancer (P = .01) was observed. CONCLUSIONS: Our study found an excess risk of death due to both liver-specific and non-liver-related causes for HBsAg-positive women in Taiwan. Effective prevention and treatment of hepatitis B virus infection is an important public health priority.

Efficient simulation of the spatial transmission dynamics of influenza.

Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies over-estimated the within-country rate of spatial spread of pandemic influenza. As large spatially-resolved data sets are constructed, the need for efficient simulation code with which to investigate the spatial patterns of the pandemic becomes clear. Here, we describe a significant improvement in the efficiency of an individual-based stochastic disease simulation framework that has been used for multiple previous studies. We quantify the efficiency of the revised algorithm and present an alternative parameterization of the model in terms of the basic reproductive number. We apply the model to the population of Taiwan and demonstrate how the location of the initial seed can influence spatial incidence profiles and the overall spread of the epidemic. Differences in incidence are driven by the relative connectivity of alternate seed locations.

Predictors and outcomes of respiratory failure among hospitalized pneumonia patients with 2009 H1N1 influenza in Taiwan.

OBJECTIVES: The worldwide outbreak of a pandemic influenza A (H1N1) virus began in April 2009. We characterized the clinical features of the hospitalized pneumonia patients with 2009 H1N1 influenza in Taiwan and elucidated the risk of those patients for developing respiratory failure. METHODS: Severe complicated influenza infection is a notifiable disease in Taiwan and the hospitalized pneumonia patients with 2009 H1N1 influenza were reported accordingly. We reviewed the medical records of the eligible cases by September 8, 2009; development of respiratory failure was the primary endpoint. RESULTS: Of the 96 patients we studied, 22 (23%) developed respiratory failure. Among those, 10 (45%) died and all of the non-respiratory failure patients survived. Age distribution, presence of dyspnea, lymphopenia, leukopenia, PaO(2)/FiO(2) ratio, PaCO(2), SOFA score, infiltration on chest x-ray at admission were different between two groups by univariate analysis. The clinical course was also different, with longer duration from onset of symptoms to use of oseltamivir, longer hospital stay, and more complications during hospitalization in patients with respiratory failure. A multivariate logistic regression showed an association between development of respiratory failure and SOFA score > or = 4 at admission, initial lymphocyte count < or = 800/microL, and the duration from symptom onset to initiation of oseltamivir > 48 h. CONCLUSIONS: Respiratory failure in patients with 2009 H1N1 influenza leads to poor outcomes, including complications and death. Clinicians could apply the three predictors at admission to identify the high-risk pneumonic patients for developing respiratory failure. Further study is needed to validate the findings of this study in other settings.

Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study.

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts. METHODS: Data on 1958 patients with hepatocellular carcinoma who were aged 6-29 years at diagnosis in Taiwan between 1983 and 2004 were collected from two national hepatocellular carcinoma registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analyzed by using Poisson regression models. All statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination program were compared for HBV immunization characteristics during infancy and prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) serostatus. RESULTS: Hepatocellular carcinoma incidence was statistically significantly lower among children aged 6-19 years in vaccinated compared with unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709 304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person-years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for persons vaccinated at birth). The risk of developing hepatocellular carcinoma for vaccinated cohorts was statistically significantly associated with incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with prenatal maternal HBeAg seropositivity (with administration of hepatitis B immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR = 9.43, 95% CI = 3.54 to 25.11). CONCLUSION: The prevention of hepatocellular carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure to prevent hepatocellular carcinoma results mostly from unsuccessful control of HBV infection by highly infectious mothers.

Hepatitis B virus infection and hepatocellular carcinoma among parous Taiwanese women: nationwide cohort study.

BACKGROUND: Few long-term studies of hepatitis B virus (HBV) infection and hepatocellular carcinoma have focused on women. We used a nationwide cohort of reproductive-aged Taiwanese women to study relationships of HBV infection and parity with hepatocellular carcinoma risk. METHODS: Prenatal test results were available for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) in the National Hepatitis B Vaccination Registry from 1 782 401 pregnant women tested from October 1, 1983, through March 31, 2000. Data from the 306 women who were diagnosed with hepatocellular carcinoma were ascertained during 15 901 722 person-years of follow-up through linkage with National Cancer Registry and National Death Certification Registry. We used Cox proportional hazards models to investigate the association of age and reproductive and serological parameters with the risk of hepatocellular carcinoma. RESULTS: Incidence rates for hepatocellular carcinoma were 0.55, 7.91, and 8.76 per 100 000 person-years among women who were HBsAg negative (ie, noncarriers), HBsAg positive plus HBeAg negative, and HBsAg positive plus HBeAg positive, respectively (compared with noncarriers, for HBsAg-positive and HBeAg-positive women, age-adjusted hazard ratio [HR] for developing hepatocellular carcinoma = 17.31, 95% confidence interval [CI] = 12.08 to 24.81; and for HBsAg-negative plus HBeAg-positive women, HR = 13.94, 95% CI = 10.34 to 18.79). Incidence rates were 0.39, 3.10, and 9.01 per 100 000 person-years, respectively, among persistent noncarriers, HBsAg-serocleared carriers, and persistent HBsAg carriers (compared with noncarriers, for HBsAg-serocleared carriers, age-adjusted HR = 7.95, 95% CI = 3.50 to 18.04; and for HBsAg persistence, HR = 23.13, 95% CI = 14.23 to 37.61). Incidence rates were 2.04, 1.55, and 1.66 per 100 000 person-years for women who had one, two, or three or more children, respectively (compared with one child, for two children, age- and HBsAg-adjusted HR = 0.68, 95% CI = 0.50 to 0.93; and for three or more children, HR = 0.63, 95% CI = 0.42 to 0.92). CONCLUSIONS: The risk for hepatocellular carcinoma was statistically significantly higher among women with chronic or active HBV infections and among those with persistent HBV infection or who underwent HBsAg seroclearance during follow-up than among HBV-unexposed women. This risk decreased as parity increased, independent of HBsAg status and age.

Assessment of changes in knowledge and stigmatization following tuberculosis training workshops in taiwan.

BACKGROUND/PURPOSE: There is little understanding of the depth of knowledge of health workers involved in tuberculosis (TB) control programs, and even less is known about health workers attaching stigma to TB patients. This study surveyed health workers enrolled in TB training workshops prior to the execution of the directly observed treatment, short course (DOTS) program. METHODS: All participants attended the training course and completed structured questionnaires before (pre-test) and after training (post-test). The questionnaires were collected immediately following completion and the scores were analyzed. RESULTS: Pair comparison of knowledge scores revealed that all participants made statistically significant improvements in level of TB knowledge, except those who had a history of TB (p = 0.331). Pair comparison of stigmatization scores revealed a reduction in stigmatization, with the DOTS workers attaching less stigma to TB patients. After training, caregivers, including women (p = 0.012), public health workers (p = 0.028), 40-49-year-old subjects (p = 0.035), those with an education of < 12 years (p = 0.024), those who had been a volunteer (p = 0.018), and those who had a history of TB and those who did not (p = 0.034, p = 0.036), were significantly less likely to stigmatize patients. TB knowledge was not found to be significantly correlated with stigmatization (pre-test, p = 0.298; post-test, p = 0.821). CONCLUSION: Training workshops in TB control were effective for promotion of knowledge and elimination of stigmatization in first-line caregivers. DOTS workers attached less stigma to TB patients than public health workers, and older workers who had been volunteers attached the least stigma.

The changing epidemiology of prevalent diagnosed HIV infections in Taiwan, 1984-2005.

By the end of 2005, there were 10,158 reported cases of HIV infections in Taiwan, of them, 2,403 had developed full blown AIDS, and 1,333 had died. It represented an average annual increase of 15% in HIV diagnoses before 2003. The most common route of transmission is through men having sex with men followed by heterosexual contact, while infections through injecting drug use (IDUs) remained low. However, the number of newly reported HIV infections has been rising sharply since 2003, mainly among IDUs. The consequences of this HIV/IDU epidemic include a rapid increase in female HIV/AIDS patients and a decreased mean age of HIV/AIDS cases. Only 2% of patients in the IDU group have been diagnosed with AIDS, suggesting that most IDU cases are in the early stage of HIV infections. HIV/AIDS patients are provided with free medical care by the government in Taiwan, including anti-retroviral treatment. The case fatality rate of AIDS cases declined gradually from 64% in 1996 to 8.9% in 2005. Patients in the IDU group seek medical care less frequently than patients in the sexual contact group. Statistics show that 61.4% of patients in the IDU group did not seek HIV-related medical care, significantly higher compared to the sexual contact group. The Taiwanese government implemented a trial "Harm Reduction Programme," which involved a needle-syringe programme (NSP) and substitution treatment, in August 2005. After 1 year's pilot study, the HIV incidence in cities with NSP decreased from 13.9 to 13.3 per 100,000 persons compared to an incidence increase from 11.5 to 15.3 per 100,000 persons in cities without NSP. We scaled up the programme to cover the whole of Taiwan in July 2006 and are expecting to see the efficacy in the near future.

Humoral and cellular immune responses to a hepatitis B vaccine booster 15-18 years after neonatal immunization.

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 plasma-derived 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)-gamma- 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-gamma- 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.