The evolutionary features and roles of single nucleotide variants and charged amino acid mutations in influenza outbreaks during NPI period.

The epidemic and outbreaks of influenza B Victoria lineage (Bv) during 2019-2022 led to an analysis of genetic, epitopes, charged amino acids and Bv outbreaks. Based on the National Influenza Surveillance Network (NISN), the Bv 72 strains isolated during 2019-2022 were selected by spatio-temporal sampling, then were sequenced. Using the Compare Means, Correlate and Cluster, the outbreak data were analyzed, including the single nucleotide variant (SNV), amino acid (AA), epitope, evolutionary rate (ER), Shannon entropy value (SV), charged amino acid and outbreak. With the emergence of COVID-19, the non-pharmaceutical interventions (NPIs) made Less distant transmission and only Bv outbreak. The 2021-2022 strains in the HA genes were located in the same subset, but were distinct from the 2019-2020 strains (P < 0.001). The codon G → A transition in nucleotide was in the highest ratio but the transversion of C → A and T → A made the most significant contribution to the outbreaks, while the increase in amino acid mutations characterized by polar, acidic and basic signatures played a key role in the Bv epidemic in 2021-2022. Both ER and SV were positively correlated in HA genes (R = 0.690) and NA genes (R = 0.711), respectively, however, the number of mutations in the HA genes was 1.59 times higher than that of the NA gene (2.15/1.36) from the beginning of 2020 to 2022. The positively selective sites 174, 199, 214 and 563 in HA genes and the sites 73 and 384 in NA genes were evolutionarily selected in the 2021-2022 influenza outbreaks. Overall, the prevalent factors related to 2021-2022 influenza outbreaks included epidemic timing, Tv, Ts, Tv/Ts, P137 (B → P), P148 (B → P), P199 (P → A), P212 (P → A), P214 (H → P) and P563 (B → P). The preference of amino acid mutations for charge/pH could influence the epidemic/outbreak trends of infectious diseases. Here was a good model of the evolution of infectious disease pathogens. This study, on account of further exploration of virology, genetics, bioinformatics and outbreak information, might facilitate further understanding of their deep interaction mechanisms in the spread of infectious diseases.

Respiratory Viral Testing Rate Patterns in Young Children Attending Tertiary Care Across Western Australia: A Population-Based Birth Cohort Study.

BACKGROUND: An understanding of viral testing rates is crucial to accurately estimate the pathogen-specific hospitalisation burden. We aimed to estimate the patterns of testing for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus (PIV) and human metapneumovirus (hMPV) by geographical location, age and time in children <5 years old in Western Australia. METHODS: We conducted a population-based cohort study of children born between 1 January 2010 and 31 December 2021, utilising linked administrative data incorporating birth and death records, hospitalisations and respiratory viral surveillance testing records from state-wide public pathology data. We examined within-hospital testing rates using survival analysis techniques and identified independent predictors of testing using binary logistic regression. RESULTS: Our dataset included 46,553 laboratory tests for RSV, influenza, PIV, or hMPV from 355,021 children (52.5% male). Testing rates declined in the metropolitan region over the study period (RSV testing in infants: from 242.11/1000 child-years in 2012 to 155.47/1000 child-years in 2018) and increased thereafter. Conversely, rates increased in non-metropolitan areas (e.g., RSV in Goldfields: from 364.92 in 2012 to 504.37/1000 child-years in 2021). The strongest predictors of testing were age <12 months (adjusted odds ratio [aOR] = 2.25, 95% CI 2.20-2.31), preterm birth (<32 weeks: aOR = 2.90, 95% CI 2.76-3.05) and remote residence (aOR = 0.77, 95% CI 0.73-0.81). CONCLUSION: These current testing rates highlight the potential underestimation of respiratory virus hospitalisations by routine surveillance and the need for estimation of the true burden of respiratory virus admissions.

Concurrent disease burden from multiple infectious diseases and the influence of social determinants in the contiguous United States.

Social determinants of health are known to underly excessive burden from infectious diseases. However, it is unclear if social determinants are strong enough drivers to cause repeated infectious disease clusters in the same location. When infectious diseases are known to co-occur, such as in the co-occurrence of HIV and TB, it is also unknown how much social determinants of health can shift or intensify the co-occurrence. We collected available data on COVID-19, HIV, influenza, and TB by county in the United States from 2019-2022. We applied the Kulldorff scan statistic to examine the relative risk of each disease by year depending on the data available. Additional analyses using the percent of the county that is below the US poverty level as a covariate were conducted to examine how much clustering is associated with poverty levels. There were three counties identified at the centers of clusters in both the adjusted and unadjusted analysis. In the poverty-adjusted analysis, we found a general shift of infectious disease burden from urban to rural clusters.

[Epidemiological characteristics of human respiratory syncytial virus in Hubei Province from 2016 to 2023].

Objective: To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023. Methods: ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed. Results: From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) (P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion: SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.

[Epidemiological characteristics of human respiratory syncytial virus in influenza-like illness in Shenzhen City from 2019 to 2023].

Objective: To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among cases presenting with influenza-like illness (ILI) in Shenzhen City from 2019 to 2023. Methods: Respiratory specimens were collected from two national sentinel hospitals in Shenzhen from March 2019 to December 2023, specifically targeting cases of ILI. The real-time PCR method was used for the detection and genotyping of HRSV. Basic demographic information was collected and used for the epidemiological analysis. Results: A total of 9 278 respiratory specimens of influenza-like cases were collected and detected, with a total positive rate of 4.77% (443/9 278) for HRSV. In 2021 (8.48%, 167/1 970), the positive rate of HRSV was significantly higher than in 2019 (3.35%, 52/1 552), 2022 (1.80%, 39/2 169), and 2023 (4.49%, 133/2 960), and the difference was statistically significant (χ2=102.395, P<0.001). The prevalence of HRSV was mainly in summer and early autumn (September), and there was an abnormal increase in the positive rate of HRSV in winter 2022. The highest positive rate of HRSV was in children under five years old (9.84%, 330/335). The typing results showed that in 2022, the prevalence of HRSV-A was predominant (71.79%, 28/39), and in 2023, HRSV-A and HRSV-B subtypes coexisted. Conclusions: The prevalence of HRSV in Shenzhen from 2019 to 2023 has obvious seasonality, mainly in summer and early autumn. Children under five years old are the main population of HRSV infections.

Analysis of seasonal H3N2 influenza virus epidemic characteristics and whole genome features in Jining City from 2018 to 2023.

Seasonal H3N2 influenza virus, known for its rapid evolution, poses a serious threat to human health. This study focuses on analyzing the influenza virus trends in Jining City (2018-2023) and understanding the evolving nature of H3N2 strains. Data on influenza-like cases were gathered from Jining City's sentinel hospitals: Jining First People's Hospital and Rencheng Maternal and Child Health Hospital, using the Chinese Influenza Surveillance Information System. Over the period from 2018 to 2023, 7844 throat swab specimens were assessed using real-time fluorescence quantitative PCR for influenza virus nucleic acid detection. For cases positive for seasonal H3N2 influenza virus, virus isolation was followed by whole genome sequencing. Evolutionary trees were built for the eight gene segments, and protein variation analysis was performed. From 2018 to 2023, influenza-like cases in Jining City represented 6.99% (237 299/3 397 247) of outpatient visits, peaking in December and January. Influenza virus was detected in 15.67% (1229/7844) of cases, primarily from December to February. Notably, no cases were found in the 2020-2021 season. Full genome sequencing was conducted on 70 seasonal H3N2 strains, revealing distinct evolutionary branches across seasons. Significant antigenic site variations in the HA protein were noted. No resistance mutations to inhibitors were found, but some strains exhibited mutations in PA, NS1, PA-X, and PB1-F2. Influenza trends in Jining City saw significant shifts in the 2020-2021 and 2022-2023 seasons. Seasonal H3N2 exhibited rapid evolution. Sustained vigilance is imperative for vaccine updates and antiviral selection.

[The definition of pandemic: causes and consequences of its adjustment in 2009 and 2011].

The article considers results of the study evaluating historical and epidemiological events that preceded and accompanied adjustment of the pandemic description on the WHO website in 2009 and 2011. The analysis covered publications related to epidemics and pandemics issues, the WHO documents, the WHO website. The descriptions of pandemic mostly focused on "enormous numbers of cases and deaths". Since May 2009, new description of pandemic was published, focusing on disease prevalence. In 2011 it reverted to initial one with no comments. From perspective of the WHO document of 2009, declaration of swine flu pandemic in June 2009 seemed justified. However, considering previous pandemic history, common sense and consequences of declaring pandemic of disease with low both number of cases and mortality, it was premature move. Since primary factor hindering development of pandemic is effectiveness of infectious disease treatment, to minimize likelihood of new pandemic it is necessary to improve special medical education quality and to study and to adapt to modern conditions all effective medications and methods used in the past.

Integrate-and-fire model of disease transmission.

We create an epidemiological susceptible-infected-susceptible model of disease transmission using integrate-and-fire nodes on a network, allowing memory of previous interactions and infections. Agents in the network sum infectious matter from their nearest neighbors at every time step, until they exceed their infection threshold, at which point they "fire" and become infected for as long as the recovery time. The model has memory of previous interactions by tracking the amount of infectious matter carried by agents as well as just binary infected or susceptible states, and the model has memory of previous infections by modeling immunity as increasing the infection threshold after recovery. Creating a simulation of the model on networks with a power-law degree distribution and homogeneous agent parameters, we find a single strain version of the model matches well with the England COVID-19 case data, with a root-mean-squared error of 0.014%. A simulation of a multistrain version of the model (where there is cross-strain immunity) matches well with the influenza strain A and strain B case numbers in Canada, with a root-mean-squared error of 0.002% and 0.0012%, respectively, though due to the coupling in the model, both strains peak in phase. Since the dynamics of the model successfully capture real-life transmission dynamics, we test interventions to study their effect on case numbers, with both quarantining and social gathering restrictions lowering the peak. Since the model has memory, the stricter the intervention, the higher the secondary peak when the restriction is removed, showing that interventions change only the shape of the curves and not the overall number infected in the population.

The Burden and Risk Factors Associated with Infectious Diseases among Refugees in a Camp for Migrants in Porto Alegre: A Cross-Sectional Survey.

Refugees usually face a disproportionate burden of infectious diseases. Recently, Brazil has experienced an influx of refugees which demands the need for scaling up public health efforts to address the challenges. The research sought to study the burden and risk factors associated with infectious diseases among refugees received in the city of Porto Alegre. This was a cross-sectional study of 261 newly arrived refugees. The study sample was predominantly composed of Venezuelans (50.6%) and Haitians (44%), male (146: 56.7%), single (30.7%), with an average age of 33.38 (± 7.30) years. The average schooling was 10.42 (± 2.09) years. Diseases with the highest prevalence were influenza, whooping cough, diphtheria, and tuberculosis. There was significant association between the country of origin and presence of symptoms for infectious and contagious diseases, which warrants targeted interventions for reducing the incidence of these diseases among refugees in Brazil.

Analysis of factors influencing influenza outbreaks in schools in Taicang City, China.

Objective: This study aims to analyze the awareness of influenza prevention and control and the behavioral attitudes toward the work among parents and staff in schools in Taicang City and the impact of the vaccination rate among students on influenza outbreaks in schools. The findings can provide references for the development of effective control strategies for the spread of influenza. Methods: An anonymous questionnaire survey was conducted on 10,962 students from 20 schools in Taicang City, with class as the unit of analysis. The survey investigated their awareness of influenza prevention and control, their attitudes, and the vaccination coverage. Results: From January to June 2023, a total of 388 influenza outbreaks were reported in schools in Taicang City, involving 77 schools. There were 3,475 confirmed cases, with an average infection rate of 18.53%. In schools where influenza outbreaks had occurred, the incidence rate of those who received influenza vaccine was significantly lower than those who did not, and the vaccine protection rate was 28.22%. The knowledge awareness rates of "the main transmission routes of influenza" and "influenza vaccination can prevent influenza" among parents of students were 95.49 and 93.16%, respectively. The differences between schools involved in the epidemic and non-epidemic were statistically significant (p < 0.05). The correct attitudes of parents toward "actively reporting relevant symptoms to teachers when their children show symptoms" and "avoiding classes with diseases when their children are suspected to be sick" are 98.80 and 96.26%, respectively. The differences between schools with and without epidemic are statistically significant (p < 0.05). The correct attitudes of the class teacher toward "correct management and control of students with flu like symptoms in the class" and "taking correct prevention and control measures in the event of a flu epidemic in the class" were 89.36 and 92.55%, respectively. The differences between epidemic related and non-epidemic related classes were statistically significant (p < 0.05). Conclusion: Enhance the knowledge level of influenza prevention and control among parents of students, Strengthening the training for class teachers in emergency response to infectious diseases and increasing vaccination coverage among students can effectively reduce the incidence of influenza and thereby the occurrence of cluster outbreaks in schools.

Risk of healthcare visits from influenza in subjects with diabetes and impacts of early vaccination.

INTRODUCTION: The objective of this study was to determine the burden of influenza disease in patients with or without diabetes in a population of American adults to understand the benefits of seasonal vaccination. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using electronic medical records totaling 1,117,263 from two Louisiana healthcare providers spanning January 2012 through December 2017. Adults 18 years or older with two or more records within the study period were included. The primary outcome quantified was influenza-related diagnosis during inpatient (IP) or emergency room (ER) visits and risk reduction with the timing of immunization. RESULTS: Influenza-related IP or ER visits totaled 0.0122-0.0169 events per person within the 2013-2016 influenza seasons. Subjects with diabetes had a 5.6-fold more frequent influenza diagnosis for IP or ER visits than in subjects without diabetes or 3.7-fold more frequent when adjusted for demographics. Early immunization reduced the risk of influenza healthcare utilization by 66% for subjects with diabetes or 67% for subjects without diabetes when compared with later vaccination for the 2013-2016 influenza seasons. Older age and female sex were associated with a higher incidence of influenza, but not a significant change in risk reduction from vaccination. CONCLUSIONS: The risk for influenza-related healthcare utilization was 3.7-fold higher if patients had diabetes during 2013-2016 influenza seasons. Early immunization provides a significant benefit to adults irrespective of a diabetes diagnosis. All adults, but particularly patients with diabetes, should be encouraged to get the influenza vaccine at the start of the influenza season.

Hospital surveillance of respiratory viruses during the COVID-19 pandemic and beyond: contribution to the WHO mosaic framework, Israel, 2020 to 2023.

BackgroundA new respiratory virus surveillance platform, based on nationwide hospital laboratory data, was established in Israel during the COVID-19 pandemic.AimWe aimed to evaluate the performance of this platform with respect to the detection of influenza and respiratory syncytial virus (RSV) from week 36 in 2020 to week 15 in 2023, and how it fits with the World Health Organization (WHO) mosaic surveillance framework.MethodsData of respiratory samples from hospitalised patients sent for laboratory confirmation of influenza virus or RSV from 25 general hospital laboratories nationwide were collected. We analysed the weekly number and percentage of samples positive for influenza virus or RSV vis-à-vis SARS-CoV-2 activity and compared data from the new surveillance platform with existing surveillance platforms. Using data in the new surveillance platform, we analysed early stages of a 2021 out-of-season RSV outbreak and evaluated the capabilities of the new surveillance system with respect to objectives and domains of the WHO mosaic framework.ResultsThe new hospital-laboratory surveillance platform captured the activity of influenza virus and RSV, provided crucial data when outpatient sentinel surveillance was not operational and supported an out-of-season RSV outbreak investigation. The new surveillance platform fulfilled important objectives in all three domains of the mosaic framework and could serve for gathering additional information to fulfil more domain objectives.ConclusionThe new hospital laboratory surveillance platform provided essential data during the COVID-19 pandemic and beyond, fulfilled important domain objectives of the mosaic framework and could be adapted for the surveillance of other viruses.

Epidemiological inference at the threshold of data availability: an influenza A(H1N2)v spillover event in the United Kingdom.

Viruses that infect animals regularly spill over into the human population, but individual events may lead to anything from a single case to a novel pandemic. Rapidly gaining an understanding of a spillover event is critical to calibrating a public health response. We here propose a novel method, using likelihood-free rejection sampling, to evaluate the properties of an outbreak of swine-origin influenza A(H1N2)v in the United Kingdom, detected in November 2023. From the limited data available, we generate historical estimates of the probability that the outbreak had died out in the days following the detection of the first case. Our method suggests that the outbreak could have been said to be over with 95% certainty between 19 and 29 days after the first case was detected, depending upon the probability of a case being detected. We further estimate the number of undetected cases conditional upon the outbreak still being live, the epidemiological parameter R 0, and the date on which the spillover event itself occurred. Our method requires minimal data to be effective. While our calculations were performed after the event, the real-time application of our method has potential value for public health responses to cases of emerging viral infection.

Ecology and evolution of avian influenza viruses.

Four types of influenza virus have been identified in nature: influenza A, B, and C viruses are capable of infecting humans, and influenzas A and B cause annual epidemics (seasonal flu) in humans; however, influenza D is currently known to infect only pigs and cattle. The influenza A viruses (IAVs) are of greatest importance to humans, causing widespread significant morbidity and mortality, and have been responsible for at least five pandemics documented since the beginning of the 20th century (Table 1). The H1N1 and H3N2 IAVs continue to circulate in humans as seasonal influenza. In addition to humans, IAVs have a wide range of host animal species in nature, especially wild aquatic birds, the reservoir hosts of IAVs. The IAVs isolated from or adapted to an avian host are named avian influenza viruses (AIVs), and are of great concern owing to their involvement in the genesis of pandemic and outbreak strains. Moreover, the majority of AIVs persist in wild birds and domestic poultry, and novel variants continue to emerge in birds and other hosts, posing non-negligible threats to host ecology and public health.

Detection of influenza virus in urban wastewater during the season 2022/2023 in Sicily, Italy.

Introduction: Seasonal influenza generally represents an underestimated public health problem with significant socioeconomic implications. Monitoring and detecting influenza epidemics are important tasks that require integrated strategies. Wastewater-based epidemiology (WBE) is an emerging field that uses wastewater data to monitor the spread of disease and assess the health of a community. It can represent an integrative surveillance tool for better understanding the epidemiology of influenza and prevention strategies in public health. Methods: We conducted a study that detected the presence of Influenza virus RNA using a wastewater-based approach. Samples were collected from five wastewater treatment plants in five different municipalities, serving a cumulative population of 555,673 Sicilian inhabitants in Italy. We used the RT-qPCR test to compare the combined weekly average of Influenza A and B viral RNA in wastewater samples with the average weekly incidence of Influenza-like illness (ILI) obtained from the Italian national Influenza surveillance system. We also compared the number of positive Influenza swabs with the viral RNA loads detected from wastewater. Our study investigated 189 wastewater samples. Results: Cumulative ILI cases substantially overlapped with the Influenza RNA load from wastewater samples. Influenza viral RNA trends in wastewater samples were similar to the rise of ILI cases in the population. Therefore, wastewater surveillance confirmed the co-circulation of Influenza A and B viruses during the season 2022/2023, with a similar trend to that reported for the weekly clinically confirmed cases. Conclusion: Wastewater-based epidemiology does not replace traditional epidemiological surveillance methods, such as laboratory testing of samples from infected individuals. However, it can be a valuable complement to obtaining additional information on the incidence of influenza in the population and preventing its spread.

Statins for the prevention of cardiovascular events associated with avian influenza: the COVID-19 pandemic as a reference.

There is growing concern that the severe respiratory disease in birds (avian influenza or 'bird flu') caused by the H5N1 influenza virus, might potentially spread more widely to humans and cause a pandemic. Here we discuss clinical issues related to human infections by the highly pathogenic H5N1 subtype of the avian influenza A virus and make a clinical comparison with recent information obtained from studies of SARS-CoV-2 infection. Firstly, we consider the potential increase in cardiovascular events in humans infected with the H5N1 virus. Like SARS-CoV-2 infection, H5N1 infection may result in endothelial dysfunction and the associated procoagulant and prothrombotic state, and via this mechanism, the infection can potentially increase cardiovascular morbidity, especially in vulnerable individuals with pre-existing cardiovascular disease. Secondly, we discuss the potential beneficial role of statin use, both in the prophylaxis and the treatment of individuals with influenza A(H5N1), as was found favorable for the treatment of COVID-19 caused by SARS-CoV-2 infection.

There is a concern that avian influenza caused by the highly pathogenic avian influenza A(H5N1) virus might potentially spread more widely to humans and result in a pandemicH5N1 infection may result in endothelial dysfunction and via this mechanism, it can potentially increase cardiovascular morbidity and mortality as has occurred with SARS-CoV-2 infection.There is a potential advantage of the use of statins to reduce cardiovascular morbidity and mortality in patients with avian influenza A(H5N1), as has been found in patients suffering from COVID-19.

Surveillance of influenza A and B viruses from community and hospital wastewater treatment plants.

Influenza virus is a well-known pathogen that can cause epidemics and pandemics. Several surveillance methods are being followed to monitor the transmission patterns and spread of influenza in the community. Wastewater-based Epidemiology (WBE) can serve as an additional tool to detect the presence of influenza viruses. The current study primarily focuses on surveillance of Influenza A and Influenza B in wastewater treatment plant (WWTP) samples. A total of 100 wastewater samples were collected in July (n = 50) and August (n = 50) 2023 from four different WWTPs in Manipal and Udupi, district of Karnataka, India. The WWTP samples were processed and tested by Real-Time reverse transcriptase PCR (RT-PCR). The data generated was analysed in comparison with the clinical Influenza cases. Of the 100 samples, 18 (18%) tested positive for Influenza A virus and 2 (2%) tested positive for Influenza B virus, with a viral load ranging 1.4 x 102-2.2 x 103 gc/L for influenza A virus and 5.2 x 103-7.7 x 103gc/L for influenza B virus. On correlating the WWTP positivity with clinical case, it was found that influenza clinical cases and virus positivity in wastewater increased simultaneously, emphasizing WBE as a concurrent method for monitoring influenza virus activity.

Increased Risk of Influenza Infection During Cold Spells in China: National Time Series Study.

Background: Studies have reported the adverse effects of cold events on influenza. However, the role of critical factors, such as characteristics of cold spells, and regional variations remain unresolved. Objective: We aimed to systematically evaluate the association between cold spells and influenza incidence in mainland China. Methods: This time series analysis used surveillance data of daily influenza from 325 sites in China in the 2014-2019 period. A total of 15 definitions of cold spells were adopted based on combinations of temperature thresholds and days of duration. A distributed lag linear model was used to estimate the short-term effects of cold spells on influenza incidence during the cool seasons (November to March), and we further explored the potential impact of cold spell characteristics (ie, intensity, duration, and timing during the season) on the estimated associations. Meta-regressions were used to evaluate the modification effect of city-level socioeconomic indicators. Results: The overall effect of cold spells on influenza incidence increased with the temperature threshold used to define cold spells, whereas the added effects were generally small and not statistically significant. The relative risk of influenza-associated with cold spells was 3.35 (95% CI 2.89-3.88), and the estimated effects were stronger during the middle period of cool seasons. The health effects of cold spells varied geographically and residents in Jiangnan region were vulnerable groups (relative risk 7.36, 95% CI 5.44-9.95). The overall effects of cold spells were positively correlated with the urban population density, population size, gross domestic product per capita, and urbanization rate, indicating a sterner response to cold spells in metropolises. Conclusions: Cold spells create a substantial health burden on seasonal influenza in China. Findings on regional and socioeconomic differences in the health effects of cold spells on seasonal influenza may be useful in formulating region-specific public health policies to address the hazardous effects of cold spells.

H5N1 influenza: Urgent questions and directions.

H5N1 is an avian influenza virus that causes respiratory disease in birds and several land and sea mammals. The recent outbreak in the United States, including infection of dairy workers, has increased the concern around potential transmission and spread. We asked virologists, epidemiologists, and public health experts what the most urgent questions and action points are at this stage of the outbreak.