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.

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.

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.

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.

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.

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.

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.

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.

Narcolepsy and 2009 H1N1 pandemic vaccination in Taiwan.

BACKGROUND: Several European countries have observed an association between narcolepsy and H1N1 vaccines containing AS03® adjuvant in children/adolescents. In Taiwan, a nationwide campaign starting November 2009 administered H1N1 vaccines without adjuvant or with MF59® adjuvant to 67% of children and 12% of adults. METHODS: For those registered in the 2000-2012 National Health Insurance (NHI) databases, we compared age-stratified (0-4, 5-18, 19-59, and ≥60 years) incidence of first referral for a diagnostic MSLT for the pre-pandemic, pandemic/pre-vaccination, and vaccination/post-pandemic period. We also compared the odds of H1N1 vaccination in each chart-ascertained narcolepsy patient, whoever had an onset of excessive daytime sleepiness between April 2009 and December 2012, with 10 population-based controls from the NHI databases on year of birth, sex, and index date, using conditional logistic regressions. RESULTS: Incidence of MSLT referral for narcolepsy was highest and significantly increased in the pandemic/pre-vaccination period in the age group 5-18 (IRR 3.40, 95% confidence intervals (CI) 2.12-5.45) and 19-59 (IRR 2.90, 95% CI 1.62-5.02) years. Among 137 confirmed narcolepsy cases (86 adults and 51 children), the odds ratios (ORs) were 1.67 (95% CI 0.81-3.45) (adults) and 1.22 (95% CI 0.62-2.39) (children) for H1N1 vaccination without adjuvant, and 1.39 (95% CI 0.17-11.48) (adults) and 3.66 (95% CI 0.37-36.02) (children) with MF59® adjuvant. CONCLUSION: No substantial association between the use of H1N1 vaccines and narcolepsy was identified in Taiwan. Instead, the H1N1 infection itself could have played a role in triggering narcolepsy in children and young adults.

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.

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.

Stockpile Model of Personal Protective Equipment in Taiwan.

The Taiwan Centers for Disease Control (Taiwan CDC) has established a 3-tier personal protective equipment (PPE) stockpiling framework that could maintain a minimum stockpile for the surge demand of PPE in the early stage of a pandemic. However, PPE stockpiling efforts must contend with increasing storage fees and expiration problems. In 2011, the Taiwan CDC initiated a stockpile replacement model in order to optimize the PPE stockpiling efficiency, ensure a minimum stockpile, use the government's limited funds more effectively, and achieve the goal of sustainable management. This stockpile replacement model employs a first-in-first-out principle in which the oldest stock in the central government stockpile is regularly replaced and replenished with the same amount of new and qualified products, ensuring the availability and maintenance of the minimum stockpiles. In addition, a joint electronic procurement platform has been established for merchandising the replaced PPE to local health authorities and medical and other institutions for their routine or epidemic use. In this article, we describe the PPE stockpile model in Taiwan, including the 3-tier stockpiling framework, the operational model, the components of the replacement system, implementation outcomes, epidemic supports, and the challenges and prospects of this model.

Undervaccination with diphtheria, tetanus, and pertussis vaccine: National trends and association with pertussis risk in young children.

BACKGROUND: The high coverage for ≥3 pertussis vaccine doses among Taiwanese children might not imply timely vaccination. Recently, resurgence of pertussis and challenges with availability of DTaP-IPV-Hib prompted this study. METHODS: In the 1996-2012 national birth cohort, we calculated the prevalence and days of undervaccination against pertussis by age 36 months. We also compared the odds of undervaccination in each laboratory-confirmed pertussis patient at ages 3-35 months with sex-, residence-, and age-matched controls from the general population, using conditional logistic regression. RESULTS: The prevalence of undervaccination was 60.6% (median 16 days) and decreasing (p < 0.0001). Among 145 cases and 2,900 controls, 58 (40.0%) and 721 (24.9%) were undervaccinated (OR 2.28, 95% CI 1.57-3.31). The attributable risk percent was 22.5% (95% CI 14.5-27.9). CONCLUSIONS: Undervaccination was decreasing. Approximately up to one-fifth pertussis cases in children aged 3-35 months could have been prevented with on-time vaccination.

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.

A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study.

BACKGROUND: Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided. MATERIALS AND METHODS: A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/µL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/µL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49-15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/µL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52-24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587-0.798) for the study cohort and 0.792 (95% CI: 0.776-0.808) and 0.766 in the 2 validation cohorts. CONCLUSIONS: A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary exposure of low-risk patients to drug toxicity and simultaneously, reduce the burden of universal treatment on the healthcare system.