A Dynamic Model for Estimating the Retention Duration of Neutralizing Antibody Titers After Vaccination in a COVID-19 Convalescent Population.

We measured neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cohort of 235 convalescent patients (representing 384 analytic samples). They were followed for up to 588 days after the first report of onset in Taiwan. A proposed Bayesian approach was used to estimate nAb dynamics in patients postvaccination. This model revealed that the titer reached its peak (1819.70 IU/mL) by 161 days postvaccination and decreased to 154.18 IU/mL by day 360. Thus, the nAb titers declined in 6 months after vaccination. Protection, against variant B.1.1.529 (ie, Omicron) may only occur during the peak period.

Preventing and controlling intra-hospital spread of COVID-19 in Taiwan - Looking back and moving forward.

COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan.

An outbreak of SARS-CoV-2 infections among people living with HIV and its successful containment-Taiwan, May to August 2021.

In Taiwan, 14,308 locally acquired COVID-19 cases among customers and employees in Sexy Tea shops were the first cases from May 9-August 28, 2021 (weeks 19-34). Nine weeks after the community spread of COVID-19 began, the proportion of people living with HIV (PLHIV) among the COVID-19 patients peaked at 35.7%, affecting 192 HIV patients, while the prevalence of HIV infection was 0.15%. In addition to a nationwide Level 3 epidemic alert, the Taiwan Centers for Disease Control (Taiwan CDC) launched four strategies to contain this outbreak among PLHIV in this prevaccine era, including improving the quality of contact tracing, delivering health information via peer navigators, expanding SARS-CoV-2 screening and encouraging vaccination, and addressing hesitancy. The outbreak of COVID-19 related to Alpha strain among PLHIV in 2021 ceased four weeks after peaking and lasted eight weeks.

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.

Outbreak of hepatitis A virus infection in Taiwan, June 2015 to September 2017.

The Taiwan Centers for Disease Control (CDC) were notified of increasing acute hepatitis A (AHA) in June 2015. Serum and/or stool from AHA patients and sewage samples were tested for hepatitis A virus (HAV). We defined outbreak cases as AHA patients with illness onset after June 2015 and with an HAV sequence less than 0.5% different from that of the TA-15 outbreak strain. We analysed characteristics and food exposures between outbreak and non-outbreak cases between January 2014 (start of enhanced surveillance) and February 2016. From June 2015 to September 2017, there were 1,563 AHA patients with a median age of 31 years (interquartile range (IQR): 26-38); the male-to-female ratio was 8.8 and 585 (37%) had human immunodeficiency virus (HIV) infection. TA-15 was detected in 82% (852/1,033) of AHA patients, and 14% (74/540) of sewage samples tested since July 2015. Infection with the TA-15 strain was associated with having HIV, sexually transmitted infections (STI), recent oral-anal sex and men who have sex with men (MSM). The Taiwan CDC implemented an HAV vaccine campaign starting from October 2016 where 62% (15,487/24,879) of people at risk were vaccinated against HAV. We recommend HAV vaccination for at-risk populations and continuous surveillance to monitor control measures.

A new reportable disease is born: Taiwan Centers for Disease Control's response to emerging Zika virus infection.

Zika virus infection, usually a mild disease transmitted through the bite of Aedes mosquitos, has been reported to be possibly associated with microcephaly and neurologic complications. Taiwan's first imported case of Zika virus infection was found through fever screening at airport entry in January 2016. No virus was isolated from patient's blood taken during acute illness; however, PCR products showed that the virus was of Asian lineage closely related to virus from Cambodia. To prevent Zika virus from spreading in Taiwan, the Taiwan Centers for Disease Control has strengthened efforts in quarantine and surveillance, increased Zika virus infection diagnostic capacity, implemented healthcare system preparedness plans, and enhanced vector control program through community mobilization and education. Besides the first imported case, no additional cases of Zika virus infection have been identified. Furthermore, no significant increase in the number of microcephaly or Guillain- Barré Syndrome has been observed in Taiwan. To date, there have been no autochthonous transmissions of Zika virus infection.

Influenza A(H5N2) virus antibodies in humans after contact with infected poultry, Taiwan, 2012.

Six persons in Taiwan who had contact with poultry infected with influenza A(H5N2) showed seroconversion for the virus by hemagglutinin inhibition or microneutralization testing. We developed an ELISA based on nonstructural protein 1 of the virus to differentiate natural infection from cross-reactivity after vaccination; 2 persons also showed seroconversion by this test.

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.

The impact of HAART initiation timing on HIV-TB co-infected patients, a retrospective cohort study.

BACKGROUND: Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan. METHODS: A population-based retrospective cohort study was conducted through linking the HIV and TB registries of Taiwan Centers for Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immune reconstitution inflammatory syndrome (IRIS), was collected through medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Cox proportional hazard model was used to explore the probability of death and IRIS after TB diagnosis by adjusting for confounding factors and factors of interest. The probability of survival and TB IRIS were calculated by the Kaplan-Meier method and compared between different HAART initiation timing groups by the log-rank test. RESULTS: There were 229 HIV-TB co-infected patients included for analysis and 60 cases (26.2%) died within one year. Besides decreasing age and increasing CD4 lymphocyte count, having started HAART during TB treatment was significantly associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06-0.21). As to the timing of HAART initiation, there was only non-significant benefit on survival among cases initiating HAART within 15 days, at 16-30 days and at 31-60 days of TB treatment than initiating after 60 days. Cases with HAART initiated after 30 days had lower risk in developing IRIS than cases with HAART initiated earlier. Cases with IRIS had significantly higher rate of re-hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days vs. 18.5 days, p < 0.01). CONCLUSION: The present study found that starting HAART during TB treatment is associated with better one-year survival, although earlier initiation within 60 days of TB treatment did not show statistical differences in survival than later initiation. Initiation of HAART within 30 days appeared to increase the risk of IRIS. Deferring HAART to 31-60 days of TB treatment might be optimal after considering the risks and benefits.

Lower prevalence of tuberculosis infection in BCG vaccinees: a cross-sectional study in adult prison inmates.

OBJECTIVES: To address whether the effect of BCG vaccination against tuberculosis (TB) infection lasts to adulthood. METHODS: A cross-sectional study on the prevalence of latent TB infection (LTBI) among HIV-negative men, using QuantiFERON-TB Gold In-tube (QFT-IT), was conducted at a prison in northern Taiwan with >3000 inmates. A QFT-IT ≥0.35 IU/ml was defined as LTBI. A QFT-IT ≥0.7 IU/ml was defined as recent LTBI. The association between the number of BCG scars and LTBI stratified by age was analysed. The study procedure was approved by the institutional review board, and all participants gave written informed consent before receiving screening tests. RESULTS: Among the 2385 participants, 25% had a QFT-IT ≥0.35 IU/ml. Increasing LTBI (14%, 32% and 50%) was observed with increased age (18-34 years, 35-54 years and ≥55 years) (p<0.001 by the Cochran-Armitage Trend Test). The number of BCG scars were found to be inversely correlated with QFT-IT results for both LTBI and recent LTBI in all three age groups (p<0.001 by Cochran-Mantel-Haenszel statistics). CONCLUSIONS: Our results suggest that BCG vaccine seems to have a protective effect in adults decades after vaccination according to the number of recent infections (QFT-IT ≥0.7 IU/ml). This finding has important implications for national policy of BCG vaccination. Further prospective cohort studies on the protective effect of BCG vaccination against TB infection in adults are warranted.

Syphilis among men who have sex with men (MSM) in Taiwan: its association with HIV prevalence, awareness of HIV status, and use of antiretroviral therapy.

To understand how awareness of HIV-positivity and the use of antiretroviral therapy associated with syphilis infection, 361 MSM attending 16 Hong-Pa (drug-and-sex parties) in Taiwan were studied. The syphilis rate of individuals within their first 2 years after HIV diagnosis (awareness) was lower than that in individuals who had not been diagnosed HIV infection prior to Hong-Pa (unawareness) (Adj OR = 0.24, P < 0.05). Notably, there was a decrease in the beneficial effect of HIV-positive status awareness on syphilis prevention with an increase in time since notification. Moreover, antiretroviral therapy was not associated with a lower incidence of syphilis, and syphilis infection peaked during the treatment dropout period. In conclusion, the duration of a protective effect of knowing one's HIV-positivity against syphilis infection was short, and the highest risk of syphilis infection was observed when patients discontinued antiretroviral therapy. Future research should examine the behavioral mechanisms involved in this prevention failure.

Seroepidemiology of measles in immune generation in Taiwan: Prevalence of neutralizing antibody and immune response to reimmunization.

BACKGROUND: Secondary vaccine failure was the principal mechanic of measles reemergence in countries with high measles vaccine coverage. The information on neutralizing antibody (nAb) prevalence, epidemiological factors of waned immunity and immune response after reimmunization was essential to measles control but largely lacking in Taiwan. METHODS: The nAb and factors of wanned immunity to measles were evaluated in a cohort of 333 subjects aged 11-30 years in 2010. The longitudinal immune response to reimmunization (n = 30) and potential virus exposure (n = 24) were assessed in young healthcare workers (HCWs) during a hospital outbreak. The nAb titer was used to define susceptibility to measles disease (<120 mIU/mL) and infection (120-900 mIU/mL). RESULTS: In the 2010 cohort, the susceptibility to measles diseases and infections was respectively identified in 35 (10.5%) and 226 (67.9%) subjects. A generalized linear model identified earlier ages of first immunization in childhood (P = 0.0214) and subjects aged ≥18 years (versus <18 years, P = 0.0425) as significant factors associated with lower nAb titers. Reimmunization of 30 seronegative HCWs resulted in seroconversion for all, with nAb titers significantly rising on day 5, peaking on day 15 and declining in month 4 post-immunization. Similar measles-specific IgG levels were observed in 24 seropositive HCWs before and 4 months after measles contact (P = 0.2352). CONCLUSION: A lack of protective immunity to measles diseases might be identified in 10% of the Taiwanese population aged 11-30 years and associated with a trend toward earlier ages of the first measles vaccination. The wanned immunity can be boosted promptly by reimmunization but with uncertain durability.

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.

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.