Slow decline of hepatitis B burden in general population: Results from a population-based survey and longitudinal follow-up study in Taiwan.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection poses a global public health threat. HBV vaccination has proven highly effective in preventing the infection; however, its long-term impact on the general population has not been addressed. We conducted analysis to determine the total and changing burden of chronic HBV infection and evaluate the serological status between vaccinated and unvaccinated in Taiwan. METHODS: Participants in "The Taiwanese Survey on Prevalence of Hyperglycemia, Hyperlipidemia and Hypertension" in 2002 (n=6602), and 4088 with follow-up survey in 2007 were included. HBsAg (including titers), anti-HBs, anti-HBc, HBeAg, anti-HBe, HBV genotypes and viral loads were assayed. Prevalence and evolving patterns of these seromarkers was compared between vaccinated and unvaccinated cohorts and predictors of persistent HBsAg positivity and negativity were examined. RESULTS: The overall prevalence of chronic HBV infection was 13·7% (95% CI, 12.9% to 14.5%) and about two thirds had past exposure (anti-HBc: 68·46%) in 2002. The vaccinated cohort tended to have lower prevalence of HBsAg and anti-HBc, and a higher proportion of anti-HBs and HBeAg positivity, genotype C and high viral load. The majority (85·42%) were consistently HBsAg negative while 12·65% were consistently positive, and 8·98% achieved seroclearance in a five-year period. In the vaccinated cohort, no subjects had acquired new exposure and became HBsAg positive, and only one (0.54%) cleared HBsAg, demonstrating the durability of vaccination through teenage and young adulthood. CONCLUSIONS: This comprehensive, population-representative-survey shows that 20 years after universal vaccination, the backlog still composed a substantial burden of chronic HBV infections in Taiwan.

Application of serologic assays for diagnosing acute hepatitis E in national surveillance of a nonendemic area.

Variant performance of immunoglobulin M (IgM) and immunoglobulin G (IgG) hepatitis E virus (HEV) assays may impact the diagnosis. The present study aimed to evaluate four different IgM/IgG assays for HEV infection for application in national surveillance in nonendemic areas. Sera from 300 patients that were stored in the Centers for Disease Control (CDC) of Taiwan for suspected acute HEV infection from 2004 to 2008, and 18 serum samples from acute cases of HEV infection in Taipei Veteran General Hospital were evaluated. Performances of EIAgen HEV IgG/M (Adaltis, Bologna, Italy), recomWell HEV IgG/M (Mikrogen, Neuried, Germany), MP HEV IgG/M (MP Biomedicals, Singapore), and in-house kits, HEVLPs (HEV virus-like particles) IgG/M were compared. Positive results of serum RNA detected by reverse transcription-polymerase chain reaction were defined as the definite diagnosis. There were five genotype 1, one genotype 3, and nine genotype 4 HEV samples. The four different IgM/IgG assays had excellent performance in terms of negative predictive value (98.4-100%) and varying performance in relation to sensitivity (66.7-93.3%) and specificity (62.9-95.6%). RecomWell IgM had the best overall performance. In addition, the combination of anti-HEV IgM ELISA with anti-HEV IgG or another anti-HEV IgM ELISA provided better screening performance, especially the recomWell IgM and HEVLPs IgM combination (area under the receiver operating curve: 0.94; sensitivity: 100%, specificity 88.1%). In conclusion, anti-HEV IgM ELISA is a good screening test for the national surveillance of acute HEV infection in nonendemic areas and not limited by inconsistent performances of sensitivity and specificity among different assays.

Neutralizing antibody response and SARS severity.

Using the Taiwan nationwide laboratory-confirmed severe acute respiratory syndrome (SARS) database, we analyzed neutralizing antibody in relation to clinical outcomes. With a linear mixed model, neutralizing antibody titer was shown to peak between week 5 and week 8 after onset and to decline thereafter, with a half-life of 6.4 weeks. Patients with a longer illness showed a lower neutralizing antibody response than patients with a shorter illness duration (p = 0.008). When early responders were compared with most patients, who seroconverted on and after week 3 of illness, the small proportion (17.4%) of early responders (antibody detectable within 2 weeks) had a higher death rate (29.6% vs. 7.8%) (Fisher exact test, p = 0.004), had a shorter survival time of <2 weeks (Fisher exact test, p = 0.013), and were more likely to be > 60 years of age (Fisher exact test, p = 0.01). Our findings have implications for understanding the pathogenesis of SARS and for SARS vaccine research and development.

Serologic and molecular biologic methods for SARS-associated coronavirus infection, Taiwan.

Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase-polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests ( neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR. With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus-based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection.