Strategically examining the full-genome of dengue virus type 3 in clinical isolates reveals its mutation spectra

BACKGROUND: Previous studies presented the quasispecies spectrum of the envelope region of dengue virus type 3 (DENV-3) from either clinical specimens or field-caught mosquitoes. However, the extent of sequence variation among full genomic sequences of DENV within infected individuals remains largely unknown. RESULTS: Instead of arbitrarily choosing one genomic region in this study, the full genomic consensus sequences of six DENV-3 isolates were used to locate four genomic regions that had a higher potential of sequence heterogeneity at capsid-premembrane (C-prM), envelope (E), nonstructural protein 3 (NS3), and NS5. The extentof sequence heterogeneity revealed by clonal sequencing was genomic region-dependent, whereas the NS3 and NS5 had lower sequence heterogeneity than C-prM and E. Interestingly, the Phylogenetic Analysis by Maximum Likelihood program (PAML) analysis supported that the domain III of E region, the most heterogeneous region analyzed, was under the influence of positive selection. CONCLUSION: This study confirmed previous reports that the most heterogeneous region of the dengue viral genome resided at the envelope region, of which the domain III was under positive selection pressure. Further studies will need to address the influence of these mutations on the overall fitness in different hosts (i.e., mosquito and human) during dengue viral transmission

Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan

Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms

Taipei's Use of a Multi-Channel Mass Risk Communication Program to Rapidly Reverse an Epidemic of Highly Communicable Disease

BACKGROUND: In 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 FINDINGS: Having 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, p<0.01). Taipei's program had a significant impact on patient compliance. Home confinement of symptomatic children increased from 10% to 60% (p<0.05) and helped curb the spread of AHC. Taipei experienced a rapid decrease in AHC cases between the Friday of the SMS announcement and the following Monday, October 15, (0.70% vs. 0.36%). By October 26, AHC cases reduced to 0.01%. The success of this risk communication program in Taipei (as compared to Keelung) is further reflected through rapid improvements in three epidemic indicators: (1) significantly lower crude attack rates (1.95% vs. 14.92%, p<0.001), (2) a short epidemic period of AHC (13 vs. 34 days), and (3) a quick drop in risk level (1 approximately 2 weeks) in Taipei districts that border Keelung (the original domestic epicenter). CONCLUSIONS AND SIGNIFICANCE: The 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

Evaluation of an Adjustable Epidemiologic Information System

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 <10 days in the following months and remained low till 2008 (0.88±1.52 days). The PSIs for newly emerged infectious diseases were 2.6 and 3.4 person-hours for H5N1 in 2007 and chikungunya in 2008, respectively, a much improvement from 1142.5 person-hours for SARS in 2003. The duration of each rubella epidemic cluster was evaluated as public health impact and showed a shortening trend (p = 0.019) that concurred with the shortening of PRT from 64.8±47.3 to 25.2±38.2 hours per cluster (p<0.0001). CONCLUSIONS/SIGNIFICANCE: The first evaluation of the novel instrument AEIS that had been used to assist Taiwan's multi-level government for infectious diseases control demonstrated that it was well integrated into the existing public health infrastructure. It provided flexible tools and computer algorithms with friendly interface for timely data collection, integration, and analysis; as a result, it shortened RTs, filled in gaps of personnel lacking sufficient experiences, created a more efficient flow of response, and identified asymptomatic/mild cases early to minimize further spreading. With further development, AEIS is anticipated to be useful in the application of other acute public health events needing immediate orchestrated data collection and public health actions

Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009–10

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<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post–peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases

Establishing a nationwide emergency department-based syndromic surveillance system for better public health responses in Taiwan

Background. With international concern over emerging infectious diseases (EID) and bioterrorist attacks, public health is being required to have early outbreak detection systems. A disease surveillance team was organized to establish a hospital emergency department-based syndromic surveillance system (ED-SSS) capable of automatically transmitting patient data electronically from the hospitals responsible for emergency care throughout the country to the Centers for Disease Control in Taiwan (Taiwan-CDC) starting March, 2004. This report describes the challenges and steps involved in developing ED-SSS and the timely information it provides to improve in public health decision-making. Methods. Between June 2003 and March 2004, after comparing various surveillance systems used around the world and consulting with ED physicians, pediatricians and internal medicine physicians involved in infectious disease control, the Syndromic Surveillance Research Team in Taiwan worked with the Real-time Outbreak and Disease Surveillance (RODS) Laboratory at the University of Pittsburgh to create Taiwan's ED-SSS. The system was evaluated by analyzing daily electronic ED data received in real-time from the 189 hospitals participating in this system between April 1, 2004 and March 31, 2005. Results. Taiwan's ED-SSS identified winter and summer spikes in two syndrome groups: influenza-like illnesses and respiratory syndrome illnesses, while total numbers of ED visits were significantly higher on weekends, national holidays and the days of Chinese lunar new year than weekdays (p < 0.001). It also identified increases in the upper, lower, and total gastrointestinal (GI) syndrome groups starting in November 2004 and two clear spikes in enterovirus-like infections coinciding with the two school semesters. Using ED-SSS for surveillance of influenza-like illnesses and enteroviruses-related infections has improved Taiwan's pandemic flu preparedness and disease control capabilities. Conclusion. Taiwan's ED-SSS represents the first nationwide real-time syndromic surveillance system ever established in Asia. The experiences reported herein can encourage other countries to develop their own surveillance systems. The system can be adapted to other cultural and language environments for better global surveillance of infectious diseases and international collaboration. © 2008 Wu et al; licensee BioMed Central Ltd

Higher Infection of Dengue Virus Serotype 2 in Human Monocytes of Patients with G6PD Deficiency

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%∼39.2%) vs 20.3%±6.2 (8.0%∼30.4%), P<0.01]. Similar observations were made of infection with the DENV-2 16681 strain [40.9%±3.9 (35.1%∼48.9%) vs 27.4%±7.1 (12.3%∼37.1%), P<0.01]. To our knowledge, this study demonstrates for the first time higher infection of human monocytes in G6PD patients with the dengue virus, which may be important in increasing epidemiological transmission and perhaps with the potential to develop more severe cases pathogenically

The Role of Imported Cases and Favorable Meteorological Conditions in the Onset of Dengue Epidemics

Dengue/dengue hemorrhagic fever is the world's most widely spread mosquito-borne arboviral disease and threatens more than two-thirds of the world's population. Cases are mainly distributed in tropical and subtropical areas in accordance with vector habitats for Aedes aegypti and Ae. albopictus. However, the role of imported cases and favorable meteorological conditions has not yet been quantitatively assessed. This study verified the correlation between the occurrence of indigenous dengue and imported cases in the context of weather variables (temperature, rainfall, relative humidity, etc.) for different time lags in southern Taiwan. Our findings imply that imported cases have a role in igniting indigenous outbreaks, in non-endemics areas, when favorable weather conditions are present. This relationship becomes insignificant in the late phase of local dengue epidemics. Therefore, early detection and case management of imported cases through timely surveillance and rapid laboratory-diagnosis may avert large scale epidemics of dengue/dengue hemorrhagic fever. An early-warning surveillance system integrating meteorological data will be an invaluable tool for successful prevention and control of dengue, particularly in non-endemic countries

Probabilistic Daily ILI Syndromic Surveillance with a Spatio-Temporal Bayesian Hierarchical Model

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