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Taiwan’s experience with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 guided its development of strategies to defend against SARS-CoV-2 in 2020, which enabled the successful control of Coronavirus disease 2019 (COVID-19) cases from 2020 through March 2021. However, in late-April 2021, the imported Alpha variant began to cause COVID-19 outbreaks at an exceptional rate in Taiwan. In this study, we aimed to determine what epidemiological conditions enabled the SARS-CoV-2 Alpha variant strains to become dominant and decline later during a surge in the outbreak. In conjunction with contact-tracing investigations, we used our bioinformatics software, CoVConvert and IniCoV, to analyze whole-genome sequences of 101 Taiwan Alpha strains. Univariate and multivariable regression analyses revealed the epidemiological factors associated with viral dominance. Univariate analysis showed the dominant Alpha strains were preferentially selected in the surge’s epicenter (p = 0.0024) through intensive human-to-human contact and maintained their dominance for 1.5 months until the Zero-COVID Policy was implemented. Multivariable regression found that the epidemic periods (p = 0.007) and epicenter (p = 0.001) were two significant factors associated with the dominant virus strains spread in the community. These dominant virus strains emerged at the outbreak’s epicenter with frequent human-to-human contact and low vaccination coverage. The Level 3 Restrictions and Zero-COVID policy successfully controlled the outbreak in the community without city lockdowns. Our integrated method can identify the epidemiological conditions for emerging dominant virus with increasing epidemiological potential and support decision makers in rapidly containing outbreaks using public health measures that target fast-spreading virus strains.

ABSTRACT: Objectives: To evaluate class suspension and mass vaccination implemented among Taipei schoolchildren during the 2009 influenza pandemic and investigate factors affecting antibody responses. Methods: We conducted 2 cohort studies on: (1) 972 schoolchildren from November 2009–March 2010 to evaluate pandemic policies and (2) 935 schoolchildren from November 2011–March 2012 to verify factors in antibody waning. Anti-influenza H1N1pdm09 hemagglutination inhibition antibodies (HI-Ab) were measured from serum samples collected before vaccination, and at 1 and 4 months after vaccination. Factors affecting HI-Ab responses were investigated through logistic regression and generalized estimating equation. Results: Seroprevalence of H1N1pdm09 before vaccination was significantly higher among schoolchildren who experienced class suspensions than those who did not (59.6% vs 47.5%, p

Abstract Emerging infectious diseases (EIDs), including the latest COVID-19 pandemic, have emerged and raised global public health crises in recent decades. Without existing protective immunity, an EID may spread rapidly and cause mass casualties in a very short time. Therefore, it is imperative to identify cases with risk of disease progression for the optimized allocation of medical resources in case medical facilities are overwhelmed with a flood of patients. This study has aimed to cope with this challenge from the aspect of preventive medicine by exploiting machine learning technologies. The study has been based on 83,227 hospital admissions with influenza-like illness and we analysed the risk effects of 19 comorbidities along with age and gender for severe illness or mortality risk. The experimental results revealed that the decision rules derived from the machine learning based prediction models can provide valuable guidelines for the healthcare policy makers to develop an effective vaccination strategy. Furthermore, in case the healthcare facilities are overwhelmed by patients with EID, which frequently occurred in the recent COVID-19 pandemic, the frontline physicians can incorporate the proposed prediction models to triage patients suffering minor symptoms without laboratory tests, which may become scarce during an EID disaster. In conclusion, our study has demonstrated an effective approach to exploit machine learning technologies to cope with the challenges faced during the outbreak of an EID.

Objectives: To evaluate the prevalence of infection prevention behaviors in Taiwan—wearing facemasks and alcohol-based hand hygiene (AHH)—and compare their practice rates during SARS and COVID-19. Methods: We surveyed 2328 Taiwanese from July 29 to August 6, 2020, assessing demographics, information sources, and preventive behaviors during the 2003 SARS outbreaks, 2009 pandemic influenza H1N1, COVID-19, and with post-survey intentions. Characteristics associated with the practice of preventive behaviors in 2020 were identified through logistic regression. Results: Preventive behaviors were conscientiously practiced by 70.2% of participants. Compared with 2003 SARS/2009 H1N1, the percentages of facemask use (66.6% vs 99.2% [indoors], P < 0.001) and on-person AHH (44.2% vs 65.4% [hand sanitizers], P < 0.001) significantly increasedduring 2020 COVID-19. Highest adherence to preventive behaviors in 2020 was among females (adjusted odds ratio [aOR], 1.72), those receiving government COVID-19 information (aOR, 1.52), participants recruited from primary-care clinics (aOR, 1.43), and those who practiced AHH during 2003 SARS/2009 H1N1 (aOR, 1.37). Conclusions: Government leadership, healthcare providers risk communication, and public cooperation rapidly mitigated the spread of COVID-19 in Taiwan even before vaccination. Future global efforts must implement such population-based preventive behaviors at a level above the viral-transmission-threshold, particularly in areas with fast-spreading SARS-CoV-2 variants.

Background The Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.Method We conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 μg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 μg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 μg of UB-612 (n = 3,875, 18–85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.Results No vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.Conclusion UB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial Registration ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.Funding UBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Abstract Background The pandemic threat of influenza has attracted great attention worldwide. To assist public health decision-makers, new suites of tools are needed to rapidly process and combine viral information retrieved from public-domain databases for a better risk assessment. Results Using our recently developed FluConvert and IniFlu software, we automatically processed and rearranged sequence data by standard viral nomenclature, determined the group-related consensus sequences, and identified group-specific polygenic signatures. The software possesses powerful ability to integrate viral, clinical, and epidemiological data. We demonstrated that both multiple basic amino acids at the cleavage site of the HA gene and also at least 11 more evidence-based viral amino acid substitutions present in global highly pathogenic avian influenza H5N2 viruses during the years 2009–2016 that are associated with viral virulence and human infection. Conclusions FluConvert and IniFlu are useful to monitor and assess all subtypes of influenza viruses with pandemic potential. These programs are implemented through command-line and user-friendly graphical interfaces, and identify molecular signatures with virological, epidemiological and clinical significance. FluConvert and IniFlu are available at https://apps.flutures.com or https://github.com/chinrur/FluConvert_IniFlu

The COVID-19 outbreak has drawn heightened attention from public health scholars researching ways to limit its spread. Much of the research has been focused on minimizing transmission in hospitals and in the general community. However, a particularly vulnerable community that has received relatively little attention is elders residing in long-term care facilities (LTCFs). In this article we address this relative lack of attention, arguing that enhanced traffic control bundling (eTCB) can and should be adopted and implemented as a means of protecting LTCF residents and staff. Enhanced TCB has been widely applied in hospital settings and has proven effective at limiting droplet and fomite transmissions both within hospitals and between hospitals and the general community. By effectively adapting eTCB to LTCF conditions, particularly by incorporating compartmentalization within zones plus active surveillance, COVID-19 transmission into and throughout LTCFs can be minimized, thereby saving numerous lives among an especially vulnerable population.

We argue that enhanced Traffic Control Bundling (eTCB) can interrupt the community-hospital-community transmission cycle, thereby limiting COVID-19’s impact. Enhanced TCB is an expansion of the traditional TCB that proved highly effective during Taiwan’s 2003 SARS outbreak. TCB’s success derived from ensuring that Health Care Workers (HCWs) and patients were protected from fomite, contact and droplet transmission within hospitals.Although TCB proved successful during SARS, achieving a similar level of success with the COVID-19 outbreak requires adapting TCB to the unique manifestations of this new disease. These manifestations include asymptomatic infection, a hyper-affinity to ACE2 receptors resulting in high transmissibility, false negatives, and an incubation period of up to 22 days. Enhanced TCB incorporates the necessary adaptations. In particular, eTCB includes expanding the TCB transition zone to incorporate a new sector – the quarantine ward. This ward houses patients exhibiting atypical manifestations or awaiting definitive diagnosis. A second adaptation involves enhancing the checkpoint hand disinfection and gowning up with Personal Protective Equipment deployed in traditional TCB. Under eTCB, checkpoint hand disinfection and donning of face masks are now required of all visitors who seek to enter hospitals.These enhancements ensure that transmissions by droplets, fomites and contact are disrupted both within hospitals and between hospitals and the broader community. Evidencing eTCB effectiveness is Taiwan’s success to date in containing and controlling the community-hospital-community transmission cycle.

A shift in dengue cases toward the adult population, accompanied by an increased risk of severe cases of dengue in the elderly, has created an important emerging issue in the past decade. To understand the level of past DENV infection among older adults after a large dengue outbreak occurred in southern Taiwan in 2015, we screened 1498 and 2603 serum samples from healthy residents aged ≥ 40 years in Kaohsiung City and Tainan City, respectively, to assess the seroprevalence of anti-DENV IgG in 2016. Seropositive samples were verified to exclude cross-reaction from Japanese encephalitis virus (JEV), using DENV/JEV-NS1 indirect IgG ELISA. We further identified viral serotypes and secondary DENV infections among positive samples in the two cities. The overall age-standardized seroprevalence of DENV-IgG among participants was 25.77% in Kaohsiung and 11.40% in Tainan, and the seroprevalence was significantly higher in older age groups of both cities. Although the percentages of secondary DENV infection in Kaohsiung and Tainan were very similar (43.09% and 44.76%, respectively), DENV-1 and DENV-2 spanned a wider age range in Kaohsiung, whereas DENV-2 was dominant in Tainan. As very few studies have obtained the serostatus of DENV infection in older adults and the elderly, this study highlights the need for further investigation into antibody status, as well as the safety and efficacy of dengue vaccination in these older populations.

In recent decades, the global incidence of dengue has increased. Affected countries have responded with more effective surveillance strategies to detect outbreaks early, monitor the trends, and implement prevention and control measures. We have applied newly developed machine learning approaches to identify laboratory-confirmed dengue cases from 4,894 emergency department patients with dengue-like illness (DLI) who received laboratory tests. Among them, 60.11% (2942 cases) were confirmed to have dengue. Using just four input variables [age, body temperature, white blood cells counts (WBCs) and platelets], not only the state-of-the-art deep neural network (DNN) prediction models but also the conventional decision tree (DT) and logistic regression (LR) models delivered performances with receiver operating characteristic (ROC) curves areas under curves (AUCs) of the ranging from 83.75% to 85.87% [for DT, DNN and LR: 84.60% ± 0.03%, 85.87% ± 0.54%, 83.75% ± 0.17%, respectively]. Subgroup analyses found all the models were very sensitive particularly in the pre-epidemic period. Pre-peak sensitivities (

The virulence of genotype I (GI) Japanese encephalitis virus (JEV) is under debate. We investigated differences in the virulence of GI and GIII JEV by calculating asymptomatic ratios based on serologic studies during GI- and GIII-JEV endemic periods. The results suggested equal virulence of GI and GIII JEV among humans.

Background/Purposes: Early diagnosis of dengue virus (DENV) infection to monitor the potential progression to hemorrhagic fever can influence the timely management of dengue-associated severe illness. Nonstructural protein 1 (NS1) antigen detection in acute serum specimens has been widely accepted as an early diagnostic assay for dengue infection; however, lower sensitivity of the NS1 antigen-capture enzyme-linked immunosorbent assay (Ag-ELISA) in secondary dengue viral infection has been reported. Methods: In this study, we developed two forms of Ag-ELISA capable of detecting E-Ag containing virion and virus-like particles, and secreted NS1 (sNS1) antigens, respectively. The temporal kinetics of viral RNA, sNS1, and E-Ag were evaluated based on the in vitro infection experiment. Meanwhile, a panel of 62 DENV-2 infected patients' sera was tested. Results: The sensitivity was 3.042 ng/mL and 3.840 ng/mL for sNS1 and E, respectively. The temporal kinetics of the appearance of viral RNA, E, NS1, and infectious virus in virus-infected tissue culture media suggested that viral RNAs and NS1 antigens could be detected earlier than E-Ag and infectious virus. Furthermore, a panel of 62 sera from patients infected by DENV Serotype 2 was tested. Treating clinical specimens with the dissociation buffer increased the detectable level of E from 13% to 92% and NS1 antigens from 40% to 85%. Conclusion: Inclusion of a low-pH glycine buffer treatment step in the commercially available Ag-ELISA is crucial for clinical diagnosis and E-containing viral particles could be a valuable target for acute DENV diagnosis, similar to NS1 detection.

ObjectivesThis study aimed to examine comprehensively the prognostic impact of underlying comorbidities among hospitalised patients with influenza-like illness (ILI) in different age groups and provide recommendations targeting the vulnerable patients.Setting and participantsA retrospective cohort of 83 227 hospitalised cases with ILI were identified from Taiwan’s National Health Insurance Research Database from January 2005 to December 2010. Cases were stratified into three different age groups: paediatric (0–17 years), adult (18–64 years) and elderly (≧65 years), and their age, sex, comorbidity and past healthcare utilisation were analysed for ILI-associated fatality.Main outcome measuresORs for ILI-related fatality in different age groups were performed using multivariable analyses with generalised estimating equation models and adjusted by age, sex and underlying comorbidities.ResultsHospitalised ILI-related fatality significantly increased with comorbidities of cancer with metastasis (adjusted OR (aOR)=3.49, 95% CI: 3.16 to 3.86), haematological malignancy (aOR=3.02, 95% CI: 2.43 to 3.74), cancer without metastasis (aOR=1.72, 95% CI: 1.54 to 1.91), cerebrovascular (aOR=1.24, 95% CI: 1.15 to 1.33) and heart diseases (aOR=1.19, 95% CI: 1.11 to 1.27) for all age groups. Adult patients with AIDS; adult and elderly patients with chronic kidney disease, tuberculosis and diabetes were significantly associated with elevated risk of death. Severe liver diseases and hypothyroidism among elderly, and dementia/epilepsy among elderly and paediatrics were distinctively associated with likelihood of ILI-related fatality.ConclusionsDifferent age-specific comorbidities were associated with increasing risk of death among hospitalised ILI patients. These findings may help update guidelines for influenza vaccination and other prevention strategies in high-risk groups for minimising worldwide ILI-related deaths.

Purifying selection during dengue viral infection has been suggested as the driving force of viral evolution and the higher complexity of the intra-host quasi-species is thought to offer an adaptive advantage for arboviruses as they cycle between arthropod and vertebrate hosts. However, very few studies have been performed to investigate the viral genetic changes within (intra-host) and between (inter-host) humans in a spatio-temporal scale. Viruses of different serotypes from various countries imported to Taiwan cause annual outbreaks. During 2001-2003, two consecutive outbreaks were caused by dengue virus serotype 2 (DENV-2) and resulted in a larger-scale epidemic with more severe dengue cases in the following year. Phylogenetic analyses showed that the viruses from both events were similar and related to the 2001 DENV-2 isolate from the Philippines. We comprehensively analyzed viral sequences from representative dengue patients and identified three consensus genetic variants, group Ia, Ib and II, with different spatio-temporal population dynamics. The phylodynamic analysis suggested group Ib variants, characterized by lower genetic diversity, transmission rate, and intra-host variant numbers, might play the role of maintenance variants. The residential locations among the patients infected by group Ib variants were in the outer rim of case clusters throughout the 2001-2003 period whereas group Ia and II variants were located in the centers of case clusters, suggesting that group Ib viruses might serve as "sheltered overwintering" variants in an undefined ecological niche. Further deep sequencing of the viral envelope (E) gene directly from individual patient serum samples confirmed the emergence of variants belonging to three quasi-species (group Ia, Ib, and II) and the ancestral role of the viral variants in the latter phase of the 2001 outbreak contributed to the later, larger-scale epidemic beginning in 2002. These findings enhanced our understanding of increasing epidemic severity over time in the same epidemic area. It also highlights the importance of combining phylodynamic and deep sequencing analysis as surveillance tools for detecting dynamic changes in viral variants, particularly searching for and monitoring any specific viral subpopulation. Such subpopulations might have selection advantages in both fitness and transmissibility leading to increased epidemic severity.

[This corrects the article DOI: 10.1371/journal.pone.0160230.].

The increasing dengue burden and epidemic severity worldwide have highlighted the need to improve surveillance. In non-endemic areas such as Taiwan, where outbreaks start mostly with imported cases from Southeast Asia, a closer examination of surveillance dynamics to detect cases early is necessary. To evaluate problems with dengue surveillance and investigate the involvement of different factors at various epidemic stages, we investigated 632 laboratory-confirmed indigenous dengue cases in Kaohsiung City, Taiwan during 2009-2010. The estimated sensitivity of clinical surveillance was 82.4% (521/632). Initially, the modified serological surveillance (targeting only the contacts of laboratory-confirmed dengue cases) identified clinically unrecognized afebrile cases in younger patients who visited private clinics and accounted for 30.4% (35/115) of the early-stage cases. Multivariate regression indicated that hospital/medical center visits [Adjusted Odds Ratio (aOR): 11.6, 95% confidence interval (CI): 6.3-21.4], middle epidemic stage [aOR: 2.4 (1.2-4.7)], fever [aOR: 2.3 (2.3-12.9)], and musculo-articular pain [aOR: 1.9 (1.05-3.3)] were significantly associated with clinical reporting. However, cases with pruritus/rash [aOR: 0.47 (0.26-0.83)] and diarrhea [aOR: 0.47 (0.26-0.85)] were underreported. In conclusion, multiple factors contributed to dengue surveillance problems. To prevent a large-scale epidemic and minimize severe dengue cases, there is a need for integrated surveillance incorporating entomological, clinical, serological, and virological surveillance systems to detect early cases, followed by immediate prevention and control measures and continuous evaluation to ensure effectiveness. This effort will be particularly important for an arbovirus, such as Zika virus, with a high asymptomatic infection ratio. For dengue- non-endemic countries, we recommend serological surveillance be implemented in areas with high Aedes mosquito indices or many breeding sites. Syndromic surveillance, spatial analysis and monitoring changes in epidemiological characteristics using a geographical information system, as well as epidemic prediction models involving epidemiological, meteorological and environmental variables will be helpful for early risk communication to increase awareness.

The largest nosocomial outbreak of Middle East respiratory syndrome (MERS) occurred in South Korea in 2015. Health Care Personnel (HCP) are at high risk of acquiring MERS-Coronavirus (MERS-CoV) infections, similar to the severe acute respiratory syndrome (SARS)-Coronavirus (SARS-CoV) infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74) and 49 (2~90) years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68) years, p = 0.006; total SARS: 42 (0~94) years, p = 0.0002]. The case fatality rates (CFR) was much lower in MERS-HCP [7.03% (9/128)] or SARS-HCP [12.24% (12/98)] than the MERS-non-HCP [36.96% (34/92), p

BackgroundHuman infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past.MethodsTwo duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved.ResultsThe DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells.ConclusionThese results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.

School children may transmit pathogens with cluster cases occurring on campuses and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City Government officials developed a School-based Infectious Disease Syndromic Surveillance System (SID-SSS). Teachers and nurses from preschools to universities in all 12 districts within Taipei are required to daily report cases of symptomatic children or sick leave requests through the SID-SSS. The pre-diagnosis at schools is submitted firstly as common pediatric disease syndrome-groups and re-submitted after confirmation by physicians. We retrieved these data from January 2010 to August 2011 for spatio-temporal analysis and evaluated the temporal trends with cases obtained from both the Emergency Department-based Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and influenza-like illness (ILI) were the two most reported syndrome groups (77.6% and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis judgments made by school teachers and nurses showed high consistency with physicians' clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly, the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance systems had the best correlation reaching 0.98 and 0.95, respectively (p

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 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.

The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas--Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post-peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p

BACKGROUND: In order to facilitate public health response and to achieve early control of infectious disease epidemics, an adjustable epidemiologic information system (AEIS) was established in the Taiwan public health network in February 2006. METHODOLOGY/PRINCIPAL FINDINGS: The performance of AEIS for the period 2006 through 2008 was evaluated based on a number of response times (RT) and the public health impact. After implementation of the system, the apparent overall shortened RT was mainly due to the shortening of personnel response time (PRT) and the time needed to draft a new questionnaire that incurred as personnel-system interface (PSI); PRT dropped from a fluctuating range of 9.8 ∼28.8 days in the first four months to

BackgroundTravelers who acquire dengue infection are often routes for virus transmission to other regions. Nevertheless, the interplay between infected travelers, climate, vectors, and indigenous dengue incidence remains unclear. The role of foreign-origin cases on local dengue epidemics thus has been largely neglected by research. This study investigated the effect of both imported dengue and local meteorological factors on the occurrence of indigenous dengue in Taiwan.Methods and principal findingsUsing logistic and Poisson regression models, we analyzed bi-weekly, laboratory-confirmed dengue cases at their onset dates of illness from 1998 to 2007 to identify correlations between indigenous dengue and imported dengue cases (in the context of local meteorological factors) across different time lags. Our results revealed that the occurrence of indigenous dengue was significantly correlated with temporally-lagged cases of imported dengue (2-14 weeks), higher temperatures (6-14 weeks), and lower relative humidity (6-20 weeks). In addition, imported and indigenous dengue cases had a significant quantitative relationship in the onset of local epidemics. However, this relationship became less significant once indigenous epidemics progressed past the initial stage.ConclusionsThese findings imply that imported dengue cases are able to initiate indigenous epidemics when appropriate weather conditions are present. Early detection and case management of imported cases through rapid diagnosis may avert large-scale epidemics of dengue/dengue hemorrhagic fever. The deployment of an early-warning surveillance system, with the capacity to integrate meteorological data, will be an invaluable tool for successful prevention and control of dengue, particularly in non-endemic countries.

Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999-2000 through the 2006-2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean +/- S.D.: 1.44+/-1.35 vs. 0.35+/-1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005-2007) than during pre-SARS winters [0.03+/-0.06 vs. 1.57+/-1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness.

BACKGROUND: For daily syndromic surveillance to be effective, an efficient and sensible algorithm would be expected to detect aberrations in influenza illness, and alert public health workers prior to any impending epidemic. This detection or alert surely contains uncertainty, and thus should be evaluated with a proper probabilistic measure. However, traditional monitoring mechanisms simply provide a binary alert, failing to adequately address this uncertainty. METHODS AND FINDINGS: Based on the Bayesian posterior probability of influenza-like illness (ILI) visits, the intensity of outbreak can be directly assessed. The numbers of daily emergency room ILI visits at five community hospitals in Taipei City during 2006-2007 were collected and fitted with a Bayesian hierarchical model containing meteorological factors such as temperature and vapor pressure, spatial interaction with conditional autoregressive structure, weekend and holiday effects, seasonality factors, and previous ILI visits. The proposed algorithm recommends an alert for action if the posterior probability is larger than 70%. External data from January to February of 2008 were retained for validation. The decision rule detects successfully the peak in the validation period. When comparing the posterior probability evaluation with the modified Cusum method, results show that the proposed method is able to detect the signals 1-2 days prior to the rise of ILI visits. CONCLUSIONS: This Bayesian hierarchical model not only constitutes a dynamic surveillance system but also constructs a stochastic evaluation of the need to call for alert. The monitoring mechanism provides earlier detection as well as a complementary tool for current surveillance programs.

BackgroundIn September 2007, an outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Keelung City and spread to Taipei City. In response to the epidemic, a new crisis management program was implemented and tested in Taipei.Methodology and principal findingsHaving noticed that transmission surged on weekends during the Keelung epidemic, Taipei City launched a multi-channel mass risk communications program that included short message service (SMS) messages sent directly to approximately 2.2 million Taipei residents on Friday, October 12th, 2007. The public was told to keep symptomatic students from schools and was provided guidelines for preventing the spread of the disease at home. Epidemiological characteristics of Taipei's outbreak were analyzed from 461 sampled AHC cases. Median time from exposure to onset of the disease was 1 day. This was significantly shorter for cases occurring in family clusters than in class clusters (mean+/-SD: 2.6+/-3.2 vs. 4.39+/-4.82 days, p = 0.03), as well as for cases occurring in larger family clusters as opposed to smaller ones (1.2+/-1.7 days vs. 3.9+/-4.0 days, pConclusions and significanceThe timely launch of this systematic, communication-based intervention proved effective at preventing a dangerous spike in AHC and was able to bring this high-risk disease under control. We recommend that public health officials incorporate similar methods into existing guidelines for preventing pandemic influenza and other emerging infectious diseases.

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency is high in Asia. An ex vivo study was conducted to elucidate the association of G6PD deficiency and dengue virus (DENV) infection when many Asian countries are hyper-endemic. Human monocytes from peripheral mononuclear cells collected from 12 G6PD-deficient patients and 24 age-matched controls were infected with one of two DENV serotype 2 (DENV-2) strains-the New Guinea C strain (from a case of dengue fever) or the 16681 strain (from a case of dengue hemorrhagic fever) with a multiplicity of infection of 0.1. The infectivity of DENV-2 in human monocytes was analyzed by flow cytometry. Experimental results indicated that the monocytes of G6PD-deficient patients exhibited a greater levels of infection with DENV-2 New Guinea C strain than did those in healthy controls [mean+/-SD:33.6%+/-3.5 (27.2% approximately 39.2%) vs 20.3%+/-6.2 (8.0% approximately 30.4%), P

Global influenza surveillance is one of the most effective strategies for containing outbreaks and preparing for a possible pandemic influenza. Since the end of 2003, highly pathogenic avian influenza viruses (HPAI) H5N1 have caused many outbreaks in poultries and wild birds from East Asia and have spread to at least 48 countries. For such a fast and wide-spreading virulent pathogen, prediction based on changes of micro- and macro-environment has rarely been evaluated. In this study, we are developing a new climatic approach by investigating the conditions that occurred before the H5N1 avian influenza outbreaks for early predicting future HPAI outbreaks and preventing pandemic disasters. The results show a temperature drop shortly before these outbreaks in birds in each of the Eurasian regions stricken in 2005 and 2006. Dust storms, like those that struck near China's Lake Qinghai around May 4, 2005, exacerbated the spread of this HPAI H5N1 virus, causing the deaths of a record number of wild birds and triggering the subsequent spread of H5N1. Weather monitoring could play an important role in the early warning of outbreaks of this potentially dangerous virus.