Seasonal Influenza Outbreaks Research Articles

Surge in Hospitalizations Associated With Mechanical Ventilator Use During Influenza Outbreaks

Information on surges in critical care services including mechanical ventilator use during seasonal influenza outbreaks is limited. To potentially facilitate preparedness plans for future pandemics, we retrospectively quantitated surges in all-cause mechanical ventilator use during peak influenza for 12 consecutive years in all certified hospitals in Maryland. Influenza testing data obtained for the Centers for Disease Control and Protection, Health and Human Services region 3, included defined peak influenza outbreak periods (PIOP), non-influenza time periods (non-ITP), and proportions of circulating influenza types for all study years. Procedure codes for mechanical ventilator use and diagnostic codes for medically attended acute respiratory illness (MAARI) were reviewed for every Maryland hospitalization. Daily counts of hospitalizations associated with ventilator use or MAARI during PIOP compared to non-ITP were analyzed using Poisson regression adjusted for month and year. Ventilator use increased during PIOP by 7% (95% CI, 5-10) over non-ITP (P < .0001) for all study years. These annual surges correlated with influenza season intensity, as measured by MAARI-related hospitalizations (correlation coefficient = 0.91, P < .0001). Surges in ventilator use were temporally associated with PIOP and were positively correlated with influenza season intensity, as measured by hospitalizations associated with acute respiratory illness. This information may assist resource planning for future pandemics. (Disaster Med Public Health Preparedness. 2014;x:1-7).

Influenzavirus B-associated acute benign myalgia cruris: An outbreak report and review of the literature

Acute benign myalgia cruris is characterized by transient bilateral calf pain that leads to difficulty walking. A regional outbreak of influenza virus B-associated myalgia cruris was observed during the seasonal influenza outbreak observed in Switzerland from week 1 to 13 of 2013. We performed a prospective case finding among the Swiss-Italian pediatric emergency units and pediatricians. A review of the literature was also performed. The diagnosis of myalgia cruris was made in 49 Swiss-Italian children aged 3.0–14years (♂:♀=1.7). Flu-like symptoms were resolving when bilateral calf pain began that remitted over ⩽7days. The creatine kinase-level, assessed in 28 patients, was elevated in 25. Nose swabs were positive for influenza virus B in 13 out of 14 cases. The blood cell count, measured in 41 cases, disclosed leucopenia in 12 and thrombocytopenia in 3. The review of the literature found 10 outbreaks of ⩾10 cases of influenza virus B-associated myalgia cruris, which included a total of 203 patients with a mean age of 7.3years and a ♂:♀ ratio of 2.0. In conclusion influenza virus B caused a large Swiss-Italian outbreak of myalgia cruris. Our outbreak and the literature indicate that influenza virus B-associated myalgia cruris affects preschool- and school-aged children, primarily boys.

Immunologic consequences of chemotherapy for ovarian cancer: Impaired responses to the influenza vaccine

ObjectivesTo examine the effect of chemotherapy for ovarian cancer on immunologic function and to define the effect on the serologic response to the influenza vaccine. MethodsUnder IRB approved protocols, patients with ovarian cancer were administered seasonal trivalent killed influenza vaccines. Peripheral blood was collected for immunologic assessments. Serum was analyzed for hemagglutination inhibition (HAI) antibody titers. Peripheral blood mononuclear cells were isolated to characterize T and B cell populations and function. ResultsThirty-one patients were recruited: 13 in remission receiving a dendritic cell vaccine with or without a single dose of low-dose cyclophosphamide, 3 in remission not receiving treatment, and 15 undergoing standard therapy. Significant effects on T cell and B cell subset distributions were seen. Functional effects were also seen. Few patients were able to mount a 4-fold HAI antibody response. A 4-fold response was observed for H1N1 in 20%, for H3N2 in 26%, and for influenza B in 6%. Pre-existing exposure to influenza was predictive of responders. ConclusionsDespite CDC recommendations that patients undergoing chemotherapy receive influenza vaccine, there is little evidence to support its serologic effectiveness in this population. Patients with ovarian cancer are almost uniformly unable to mount a meaningful antibody response. These findings have serious implications for future resource allocation for both seasonal and novel pandemic influenza outbreak and understanding the immunologic deficits as a result of chemotherapy may improve patient care.

Effective School Actions for Mitigating Seasonal Influenza Outbreaks in Niigata, Japan

BackgroundJapan has implemented various school actions during seasonal influenza outbreaks since the 1950's under the School Health Law. However, the effective duration, extent, and timing of closures remain unresolved.Materials and MethodsWe conducted a retrospective study on the relationship between elementary class closures and influenza outbreak control during four consecutive influenza seasons from the 2004-2005 to 2007-2008 school years in Joetsu, Niigata, Japan. Among a total of 1,061 classes of 72 schools, 624 cases of influenza outbreaks were documented among 61 schools.ResultsClass closures were carried out in a total of 62 cases in response to influenza outbreak, which was defined as a student absentee rate of greater than 10% due to influenza or influenza-like illness. Of these cases, two-day class closures were conducted the day after reaching a 10% student absentee rate in 28 cases and other types of closures were initiated in 34 cases. A markedly higher number of outbreak cases ended within one week for two-day class closures compared to the other types of closures (82.1% vs. 20.6%, respectively). The significant association between two-day class closures and interruption of an outbreak within one week was confirmed using a multivariable model adjusted for the season, grade, day of the week of an outbreak start, and absentee rate on the day of an outbreak start (OR, 3.18; 95% CI, 1.12–9.07; p = 0.030).ConclusionsOur results suggest that a two-day class closure carried out the day after reaching a 10% absentee rate is an effective approach for mitigating influenza outbreaks in elementary schools.

Endocine™, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination

Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

Management Insights

Management Insights

A Game-Theoretic Model of International Influenza Vaccination Coordination

Influenza vaccination decisions in one country can influence the size of an outbreak in other countries due to interdependent risks from infectious disease transmission. This paper examines the inefficiency in the allocation of influenza vaccines that is due to interdependent risk of infection across borders and proposes a contractual mechanism to reduce such inefficiencies. The proposed contract is based on an epidemic model that accounts for intranational transmission and that from a source country where the dominant strain emerges. The contract reduces the overall financial burden of infection globally and improves the total number infected by seasonal influenza outbreaks. This is consistent with recent recommendations to improve pandemic preparedness. Numerical experiments demonstrate that the benefits of the contract can prevent millions of influenza cases and save tens of millions of dollars, and that the benefits are even greater when cross-border transmission is higher, even if cross-border transmission parameters have moderate estimation errors. This paper was accepted by Martin Lariviere, operations management.

A Simulation Optimization Approach to Epidemic Forecasting.

Reliable forecasts of influenza can aid in the control of both seasonal and pandemic outbreaks. We introduce a simulation optimization (SIMOP) approach for forecasting the influenza epidemic curve. This study represents the final step of a project aimed at using a combination of simulation, classification, statistical and optimization techniques to forecast the epidemic curve and infer underlying model parameters during an influenza outbreak. The SIMOP procedure combines an individual-based model and the Nelder-Mead simplex optimization method. The method is used to forecast epidemics simulated over synthetic social networks representing Montgomery County in Virginia, Miami, Seattle and surrounding metropolitan regions. The results are presented for the first four weeks. Depending on the synthetic network, the peak time could be predicted within a 95% CI as early as seven weeks before the actual peak. The peak infected and total infected were also accurately forecasted for Montgomery County in Virginia within the forecasting period. Forecasting of the epidemic curve for both seasonal and pandemic influenza outbreaks is a complex problem, however this is a preliminary step and the results suggest that more can be achieved in this area.

Towards a Personalised Approach to Managing Influenza Infections in Infants and Children – Food for Thought and a Note on Oseltamivir

Acute respiratory infections represent common diseases in childhood and a challenge to infection control, public heath, and the clinical management of patients and their families. Children are avid spreaders of respiratory viruses, and seasonal outbreaks of influenza create additional disease burden and healthcare cost. Infants under the age of two and children with chronic conditions are at high risk. The absence of pre-defined risk factors however, does not protect from serious disease. Immunisation rates remain low, and physical interventions are of limited value in young children. Children with influenza may be contagious prior to the onset of symptoms, and school closures have been shown to have a temporary effect at most. The timely detection of influenza in at-risk patients is important to prevent hospital-based transmission and influenza-associated morbidity and mortality. Guidelines issued by professional associations and public health agencies need to be translated into everyday clinical practice. Antiviral therapy should be initiated early and monitored closely, including virologic and clinical outcomes. The duration of treatment and the decision to readmit children to schools and kindergartens should be adjusted to the individual child patient using evidence-based clinical and virologic criteria. This article presents lessons learnt from a quality management program for infants and children with influenza-like illness at the Charite Department of Paediatrics in collaboration with the National Reference Centre for Influenza at the Robert Koch Institute, in Berlin, Germany. The Charité Influenza-Like Disease (ChILD) Cohort was established during the 2009 influenza pandemic and encompasses nearly 4000 disease episodes to date.

Commentary

Commentary

Predictors of indoor absolute humidity and estimated effects on influenza virus survival in grade schools

BackgroundLow absolute humidity (AH) has been associated with increased influenza virus survival and transmissibility and the onset of seasonal influenza outbreaks. Humidification of indoor environments may mitigate viral transmission and may be an important control strategy, particularly in schools where viral transmission is common and contributes to the spread of influenza in communities. However, the variability and predictors of AH in the indoor school environment and the feasibility of classroom humidification to levels that could decrease viral survival have not been studied.MethodsAutomated sensors were used to measure temperature, humidity and CO2 levels in two Minnesota grade schools without central humidification during two successive winters. Outdoor AH measurements were derived from the North American Land Data Assimilation System. Variability in indoor AH within classrooms, between classrooms in the same school, and between schools was assessed using concordance correlation coefficients (CCC). Predictors of indoor AH were examined using time-series Auto-Regressive Conditional Heteroskedasticity models. Classroom humidifiers were used when school was not in session to assess the feasibility of increasing indoor AH to levels associated with decreased influenza virus survival, as projected from previously published animal experiments.ResultsAH varied little within classrooms (CCC >0.90) but was more variable between classrooms in the same school (CCC 0.81 for School 1, 0.88 for School 2) and between schools (CCC 0.81). Indoor AH varied widely during the winter (range 2.60 to 10.34 millibars [mb]) and was strongly associated with changes in outdoor AH (p < 0.001). Changes in indoor AH on school weekdays were strongly associated with CO2 levels (p < 0.001). Over 4 hours, classroom humidifiers increased indoor AH by 4 mb, an increase sufficient to decrease projected 1-hour virus survival by an absolute value of 30% during winter months.ConclusionsDuring winter, indoor AH in non-humidified grade schools varies substantially and often to levels that are very low. Indoor results are predicted by outdoor AH over a season and CO2 levels (which likely reflects human activity) during individual school days. Classroom humidification may be a feasible approach to increase indoor AH to levels that may decrease influenza virus survival and transmission.

Parallel Programming Approaches for an Agent-based Simulation of Concurrent Pandemic and Seasonal Influenza Outbreaks

In this paper we propose parallelized versions of an agent-based simulation for concurrent pandemic and seasonal influenza outbreaks. The objective of the implementations is to significantly reduce the replication time and allow faster evaluation of mitigation strategies during an ongoing emergency. The simulation was initially parallelized using the g++ OpenMP library. We simulated the outbreak in a population of 1,000,000 individuals to evaluate algorithm performance and results. In addition to the OpenMP parallelization, a proposed CUDA implementation is also presented.

Influenza Virus-like Particle Containing Two Different Subtypes of Hemagglutinin Confers Protection in Mice Against Lethal Challenge With A/PR8 (H1N1) and A/HK (H3N2) Viruses

BackgroundPreventing the seasonal or pandemic outbreak of influenza can be powerful and cost-effective.ObjectivesIn this study, we constructed a novel virus-like particle (VLP) platform that contains two hemagglutinin (HA) subtypes and evaluated immunogenicity of constructed VLP in mice.Materials and MethodsThis recombinant candidate vaccine model resulted in the expression of two HAs of H1N1 and H3N2 subtypes co-localized within a VLP. Following infection of insect cells with recombinant baculovirus co-expressing H1, H3 and M1 proteins, VLPs with size of 80–120 nm were self-assembled, budding, and released into the insect culture medium. The resulting VLPs which contained two different subtypes of hemagglutinin were purified by ultracentrifugation. The immunogenicity of VLPs was evaluated in mice following immunization.ResultsOur data showed that vaccination using VLPs elicited robust levels of serum IgG, and viral neutralizing antibodies against A/PR8 (H1N1) and A/HK (H3N2) viruses. Following challenge with lethal dose of A/PR8 (H1N1) and A/HK (H3N2, vaccinated mice were protected, displaying no sign of weight loss and mortality compared to non-vaccinated control mice.ConclusionsVLPs can serve as a promising vaccination strategy to control influenza virus.

School closures and influenza: systematic review of epidemiological studies

ObjectiveTo review the effects of school closures on pandemic and seasonal influenza outbreaks.DesignSystematic review.Data sourcesMEDLINE and EMBASE, reference lists of identified articles, hand searches of key journals and additional papers...

Forecasting seasonal outbreaks of influenza

Influenza recurs seasonally in temperate regions of the world; however, our ability to predict the timing, duration, and magnitude of local seasonal outbreaks of influenza remains limited. Here we develop a framework for initializing real-time forecasts of seasonal influenza outbreaks, using a data assimilation technique commonly applied in numerical weather prediction. The availability of real-time, web-based estimates of local influenza infection rates makes this type of quantitative forecasting possible. Retrospective ensemble forecasts are generated on a weekly basis following assimilation of these web-based estimates for the 2003-2008 influenza seasons in New York City. The findings indicate that real-time skillful predictions of peak timing can be made more than 7 wk in advance of the actual peak. In addition, confidence in those predictions can be inferred from the spread of the forecast ensemble. This work represents an initial step in the development of a statistically rigorous system for real-time forecast of seasonal influenza.

Synchronous Dynamics of Observed and Predicted Values of Anti-influenza drugs in Environmental Waters during a Seasonal Influenza Outbreak

Time-dependent dynamics in the concentrations of four anti-influenza drugs (oseltamivir, oseltamivir carboxylate, zanamivir, and amantadine) in environmental waters collected from the Yodo River basin, Japan, were monitored for the first time over a 1 year period (July 2010 to June 2011). The clear, convex dynamic profiles of oseltamivir, oseltamivir carboxylate, and zanamivir during a 3 month seasonal influenza outbreak (January to March 2011) were synchronized well with that of the numbers of influenza patients treated with the drugs. The highest levels in sewage treatment plants (STPs) and river waters were, respectively, 177 and 60 ng/L (oseltamivir), 827 and 288 ng/L (oseltamivir carboxylate), and 30 and 15 ng/L (zanamivir). Fixed levels of amantadine were detectable year-round (100-200 ng/L in the STPs and 10-30 ng/L in river waters). The predicted convex profiles of oseltamivir, oseltamivir carboxylate, and zanamivir in both STPs and river waters were significantly correlated (0.714 < R < 0.932) with the observed values. The profiles were predicted successfully by simple mathematical principles, taking the number of influenza patients, quantities of Tamiflu and Relenza used, dilution by drainwaters passing through STPs, removal rates at STPs, dilution rates in river effluents, and attenuation rates in rivers into consideration.

Modeling and Statistical Analysis of the Spatio-Temporal Patterns of Seasonal Influenza in Israel

BackgroundSeasonal influenza outbreaks are a serious burden for public health worldwide and cause morbidity to millions of people each year. In the temperate zone influenza is predominantly seasonal, with epidemics occurring every winter, but the severity of the outbreaks vary substantially between years. In this study we used a highly detailed database, which gave us both temporal and spatial information of influenza dynamics in Israel in the years 1998–2009. We use a discrete-time stochastic epidemic SIR model to find estimates and credible confidence intervals of key epidemiological parameters.FindingsDespite the biological complexity of the disease we found that a simple SIR-type model can be fitted successfully to the seasonal influenza data. This was true at both the national levels and at the scale of single cities.The effective reproductive number Re varies between the different years both nationally and among Israeli cities. However, we did not find differences in Re between different Israeli cities within a year. R e was positively correlated to the strength of the spatial synchronization in Israel. For those years in which the disease was more “infectious”, then outbreaks in different cities tended to occur with smaller time lags. Our spatial analysis demonstrates that both the timing and the strength of the outbreak within a year are highly synchronized between the Israeli cities. We extend the spatial analysis to demonstrate the existence of high synchrony between Israeli and French influenza outbreaks.ConclusionsThe data analysis combined with mathematical modeling provided a better understanding of the spatio-temporal and synchronization dynamics of influenza in Israel and between Israel and France. Altogether, we show that despite major differences in demography and weather conditions intra-annual influenza epidemics are tightly synchronized in both their timing and magnitude, while they may vary greatly between years. The predominance of a similar main strain of influenza, combined with population mixing serve to enhance local and global influenza synchronization within an influenza season.

Influential Group Backs Mandatory Flu Shots

Seasonal influenza vaccination should be required for all health care workers, according to updated seasonal and pandemic influenza principles from the Infectious Diseases Society of America. Incorporating lessons learned during the 2009–2010 H1N1 influenza pandemic and warning against complacency about the inevitability of another pandemic, the revised IDSA principles debuted Sept. 14. AMDA has long supported mandatory influenza vaccination for “every long-term health care worker who has direct patient contact unless a medical contraindication or religious objection exists.” The IDSA revamped its flu guidance to help Department of Health and Human Services officials establish priorities as they implement the Pandemic and All-Hazards Preparedness Act, which is being reauthorized by Congress. IDSA last released such flu preparation and response principles in January 2007, long before the 2009 H1N1 influenza pandemic. The emergence of the novel influenza H1N1 strain showed that “in addition to severe illness and death, the spread of new influenza strains can cause significant societal and economic disruption and anxiety, and, in extreme cases, may threaten economic and national security.” The document outlines 10 principles, including strengthening influenza vaccination efforts and boosting the accuracy and availability of diagnostic tools. It calls for enhanced availability of current antiviral drugs and the development of new, simple-to-use antiviral drugs. The document highlights the need for antibacterial drugs to treat secondary infections. IDSA also addresses the need to protect health care workers during seasonal and pandemic influenza outbreaks, and it recommends that annual seasonal influenza vaccination be required for all health care workers “through rules, regulations, policies, or laws.” During a pandemic, health care workers directly taking care of patients should be in the group with highest vaccination priority. And long-term prophylaxis with antivirals can be considered “when medically appropriate and as supplies permit.” There were almost 61 million influenza cases reported in the United States during the 2009 H1N1 pandemic, including 274,000 hospitalizations and 12,500 deaths, according to IDSA. About 10% of deaths occurred in people age 65 and older.

Prevention of influenza among travellers attending at a UK travel clinic: beliefs and perceptions. A cross-sectional study.

Please cite this paper as: Masuet‐Aumatell et al. (2012) Prevention of influenza among travellers attending at a UK travel clinic: beliefs and perceptions. A cross‐sectional study. Influenza and Other Respiratory Viruses 7(4), 574–583. Background Travellers’ compliance with measures to prevent influenza through the use of antivirals and influenza vaccine remains very poor despite influenza being one of the commonest travel and vaccine‐preventable diseases. A study was undertaken to assess travellers’ beliefs, perceptions and intentions to take antivirals for the treatment and prevention of influenza during the H1N1 pandemic. Methods A cross‐sectional survey (n = 96) of travellers who attended the Royal Free Travel Health Centre, London, UK was undertaken in September 2009. A self‐administered questionnaire was completed by a traveller in advance of their pre‐travel health consultation. Logistic regression identified variables independently associated with compliance. Results Influenza vaccination uptake for the 5 years preceding the study was found to be 20·8%. This was statistically significantly higher for older travellers and those with underlying health conditions (P < 0·005). Mean intention to comply with antiviral drugs on a preventive and therapeutic basis was 58% and 72%, respectively, and this varied markedly with age and with dispensed antimalarial chemoprophylaxis. Conclusion This study identifies some beliefs and perceptions travellers consider with regard to the therapeutic and preventive influenza use of antivirals during the H1N1 pandemic; it underscores the importance of travellers receiving hemisphere appropriate influenza vaccination. The external validity of these study findings requires further corroboration involving other travel clinics and different cohorts of travellers during seasonal activity or outbreaks of influenza. These findings could guide the development of future strategies for the prevention of influenza in travellers.

Research progress on influenza antiviral small RNAs

Worldwide influenza caused by influenza virus is a respiratory disease which threats the public health by seasonal epidemics or global influenza outbreak. Vaccines and drugs are current therapies, but there are many restricted factors such as neurotoxicity, side effects of gastrointestinal, and drug resistance. New technologies, particularly RNAi mediated by small RNAs, has become a potential and robust method in influenza antiviral research for its high efficiency, specific, and speedy. Following the spread and epidemic of the influenza virus, application of small RNAs into influenza antiviral research has been reported increasingly. The small RNAs, PA-2087, NP-1496, and M-950, which targets PA, NP, and M2 genes, respectively, are the most effective anti-influenza siRNAs up to now. siRNA of targeting conservative region of different influenza viral genes has broader effect on virus inhibition. The combination of siRNAs of targeting different genes can achieve better virus inhibition. In this review, we mainly described the progress of siRNAs and miRNAs for anti-influenza virus, and the prospects and hurdles of influenza RNAi therapy as well.