Comparison of Estimated Effectiveness of Case-Based and Population-Based Interventions on COVID-19 Containment in Taiwan.

Importance: Taiwan is one of the few countries with initial success in COVID-19 control without strict lockdown or school closure. The reasons remain to be fully elucidated. Objective: To compare and evaluate the effectiveness of case-based (including contact tracing and quarantine) and population-based (including social distancing and facial masking) interventions for COVID-19 in Taiwan. Design, Setting, and Participants: This comparative effectiveness study used a stochastic branching process model using COVID-19 epidemic data from Taiwan, an island nation of 23.6 million people, with no locally acquired cases of COVID-19 reported for 253 days between April and December 2020. Main Outcomes and Measures: Effective reproduction number of COVID-19 cases (the number of secondary cases generated by 1 primary case) and the probability of outbreak extinction (0 new cases within 20 generations). For model development and calibration, an estimation of the incubation period (interval from exposure to symptom onset), serial interval (time between symptom onset in an infector-infectee pair), and the statistical distribution of the number of any subsequent infections generated by 1 primary case was calculated. Results: This study analyzed data from 158 confirmed COVID-19 cases (median age, 45 years; interquartile range, 25-55 years; 84 men [53%]). An estimated 55% (95% credible interval [CrI], 41%-68%) of transmission events occurred during the presymptomatic stage. In our estimated analysis, case detection, contact tracing, and 14-day quarantine of close contacts (regardless of symptoms) was estimated to decrease the reproduction number from the counterfactual value of 2.50 to 1.53 (95% CrI, 1.50-1.57), which would not be sufficient for epidemic control, which requires a value of less than 1. In our estimated analysis, voluntary population-based interventions, if used alone, were estimated to have reduced the reproduction number to 1.30 (95% CrI, 1.03-1.58). Combined case-based and population-based interventions were estimated to reduce the reproduction number to below unity (0.85; 95% CrI, 0.78-0.89). Results were similar for additional analyses with influenza data and sensitivity analyses. Conclusions and Relevance: In this comparative effectiveness research study, the combination of case-based and population-based interventions (with wide adherence) may explain the success of COVID-19 control in Taiwan in 2020. Either category of interventions alone would have been insufficient, even in a country with an effective public health system and comprehensive contact tracing program. Mitigating the COVID-19 pandemic requires the collaborative effort of public health professionals and the general public.

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset.

Importance: The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. Objective: To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. Design, Setting, and Participants: This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020. Main Outcomes and Measures: Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). Results: We enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 44 men and 56 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). Conclusions and Relevance: In this study, high transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.

Improving the Use of Mortality Data in Public Health: A Comparison of Garbage Code Redistribution Models.

Objectives. To describe and compare 3 garbage code (GC) redistribution models: naïve Bayes classifier (NB), coarsened exact matching (CEM), and multinomial logistic regression (MLR).Methods. We analyzed Taiwan Vital Registration data (2008-2016) using a 2-step approach. First, we used non-GC death records to evaluate 3 different prediction models (NB, CEM, and MLR), incorporating individual-level information on multiple causes of death (MCDs) and demographic characteristics. Second, we applied the best-performing model to GC death records to predict the underlying causes of death. We conducted additional simulation analyses for evaluating the predictive performance of models.Results. When we did not account for MCDs, all 3 models presented high average misclassification rates in GC assignment (NB, 81%; CEM, 86%; MLR, 81%). In the presence of MCD information, NB and MLR exhibited significant improvement in assignment accuracy (19% and 17% misclassification rate, respectively). Furthermore, CEM without a variable selection procedure resulted in a substantially higher misclassification rate (40%).Conclusions. Comparing potential GC redistribution approaches provides guidance for obtaining better estimates of cause-of-death distribution and highlights the significance of MCD information for vital registration system reform.

Spatially Adjusted Time-varying Reproductive Numbers: Understanding the Geographical Expansion of Urban Dengue Outbreaks.

The basic reproductive number (R0) is a fundamental measure used to quantify the transmission potential of an epidemic in public health practice. However, R0 cannot reflect the time-varying nature of an epidemic. A time-varying effective reproductive number Rt can provide more information because it tracks the subsequent evolution of transmission. However, since it neglects individual-level geographical variations in exposure risk, Rt may smooth out interpersonal heterogeneous transmission potential, obscure high-risk spreaders, and hence hamper the effectiveness of control measures in spatial dimension. Therefore, this study proposes a new method for quantifying spatially adjusted (time-varying) reproductive numbers that reflects spatial heterogeneity in transmission potential among individuals. This new method estimates individual-level effective reproductive numbers (Rj) and a summarized indicator for population-level time-varying reproductive number (Rt). Data from the five most severe dengue outbreaks in southern Taiwan from 1998-2015 were used to demonstrate the ability of the method to highlight early spreaders contributing to the geographic expansion of dengue transmission. Our results show spatial heterogeneity in the transmission potential of dengue among individuals and identify the spreaders with the highest Rj during the epidemic period. The results also reveal that super-spreaders are usually early spreaders that locate at the edges of the epidemic foci, which means that these cases could be the drivers of the expansion of the outbreak. Therefore, our proposed method depicts a more detailed spatial-temporal dengue transmission process and identifies the significant role of the edges of the epidemic foci, which could be weak spots in disease control and prevention.

Is Hyperuricemia, an Early-Onset Metabolic Disorder, Causally Associated with Cardiovascular Disease Events in Han Chinese?

BACKGROUND: Serum uric acid (SUA) has gradually been recognized as a potential risk factor for cardiovascular disease (CVD). However, whether the relationship is causal remains controversial. METHODS: We employed two methods to demonstrate the importance of SUA in CVD development. First, we examined the onset sequence of hyperuricemia in relation to five cardiometabolic (CM) diseases. Second, we conducted a Mendelian randomization (MR) study to causally infer the relationship between SUA and CVD. The information collected from the Cardiovascular Disease Risk Factors Two-Township Study (CVDFACTS) and Taiwan Biobank was used, respectively. RESULTS: The onset sequence study showed that hyperuricemia and hypo-alpha-lipoproteinemia (low HDL-C) have earlier ages of onset than other CM diseases. For the MR analysis, the high weighted genetic risk score (WGRS) group had a significantly increased cumulative lifetime risk of CVD compared with the low WGRS group (OR = 1.62, (1.17-2.23), P = 0.003). Sensitivity analysis using the WGRS derived from other populations' SUA-influential SNPs revealed similar results. CONCLUSIONS: We showed that hyperuricemia is an earlier-onset metabolic disorder than hypertension, hypertriglyceridemia, and diabetes mellitus, indicating that high SUA plays an upstream role in CM development. Moreover, our MR study results support the idea that hyperuricemia may play a causal role in CVD development. Further validation studies in more populations are needed.