Disease spreading through human travel networks has been a topic of great interest in recent years, as witnessed during outbreaks of influenza A (H1N1) or SARS pandemics. One way to stop spreading over the airline network are travel restrictions for major airports or network hubs based on the total number of passengers of an airport. Here, we test alternative strategies using edge removal, cancelling targeted flight connections rather than restricting traffic for network hubs, for controlling spreading over the airline network. We employ a SEIR metapopulation model that takes into account the population of cities, simulates infection within cities and across the network of the top 500 airports, and tests different flight cancellation methods for limiting the course of infection. The time required to spread an infection globally, as simulated by a stochastic global spreading model was used to rank the candidate control strategies. The model includes both local spreading dynamics at the level of populations and long-range connectivity obtained from real global airline travel data. Simulated spreading in this network showed that spreading infected 37% less individuals after cancelling a quarter of flight connections between cities, as selected by betweenness centrality. The alternative strategy of closing down whole airports causing the same number of cancelled connections only reduced infections by 18%. In conclusion, selecting highly ranked single connections between cities for cancellation was more effective, resulting in fewer individuals infected with influenza, compared to shutting down whole airports. It is also a more efficient strategy, affecting fewer passengers while producing the same reduction in infections.

Background

A substantial recrudescent wave of pandemic influenza A/H1N1 that began in December 2011 is ongoing and has not yet peaked in Mexico, following a 2-year period of sporadic transmission. Mexico previously experienced three pandemic waves of A/H1N1 in 2009, associated with higher excess mortality rates than those reported in other countries, and prompting a large influenza vaccination campaign. Here we describe changes in the epidemiological patterns of the ongoing 4th pandemic wave in 2011-12, relative to the earlier waves in 2009. The analysis is intended to guide public health intervention strategies in near real time.

Methods

We analyzed demographic and geographic data on all hospitalizations with acute respiratory infection (ARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-April 2009 to 10-Feb 2012. We characterized the age and regional patterns of A/H1N1-positive hospitalizations and inpatient-deaths relative to the 2009 A/H1N1 influenza pandemic. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset.

Results

A total of 5,795 ARI hospitalizations and 186 inpatient-deaths (3.2%) were reported between 01-December 2011 and 10-February 2012 (685 A/H1N1-positive inpatients and 75 A/H1N1-positive deaths). The nationwide peak of daily ARI hospitalizations in early 2012 has already exceeded the peak of ARI hospitalizations observed during the major fall pandemic wave in 2009. The mean age was 34.3 y (SD=21.3) among A/H1N1 inpatients and 43.5 y (SD=21) among A/H1N1 deaths in 2011-12. The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among seniors >=60 years of age (Chi-square test P<0.001) and lower among younger age groups (Chi-square test, P<0.03) for the 2011-2012 pandemic wave, compared to the earlier waves in 2009. The reproduction number of the winter 2011-12 wave in central Mexico was estimated at 1.2-1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009.

Conclusions

We have documented a substantial and ongoing increase in the number of ARI hospitalizations during the period December 2011-February 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths, relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is reminiscent of historical pandemics and indicates either a gradual drift in the A/H1N1 virus, and/or a build-up of immunity among younger populations.

In 2010, H14 influenza A viruses were recovered from clinically normal sea ducks in the United States. These are the first H14 isolates recovered in the Western Hemisphere and represent the only documented H14 influenza A viruses isolated since the original isolates were recovered from near the Caspian Sea during 1982.

While the 1918/1919 H1N1 influenza pandemic is widely recognized as a “worst-case scenario” for the emergence of a new influenza strain, relatively little is known about the origin of the responsible virus and its pattern of spread. Most studies of this virus in the United States rely on temporally and spatially aggregated data. Location-specific studies of the impact of the 1918 pandemic strain in the United States have been confined primarily to large cities on the East Coast or West Coast. In this study, data on pneumonia and influenza fatalities from 1910-1923 have been extracted from death certificates for Saint Joseph, Missouri, a typical mid-sized city in the central United States. An increase in pneumonia and influenza mortality was noted starting in the 1915/1916 influenza season. Initially, increased mortality was observed in infants and the elderly. In February 1918, an age-shift typical of pandemic strains of virus was seen, as the burden of mortality shifted to young adults, a characteristic of the 1918 pandemic virus. These results provide one of the first confirmations of the existence of a “herald wave” of influenza activity in the United States prior to the recognized start of the H1N1 pandemic in Spring 1918. This study is one of very few that measures the impact of 1918/1919 influenza in a particular location in the central United States.

To gain insight into the possible origin of a new reassortant influenza A virus between pandemic (H1N1) 2009 and endemic swine viruses that has jumped the species barrier and caused a few infections among humans in Indiana and Pennsylvania recently, we analyzed all full genome sequences related to this virus and report its evolutionary history, but failed to determine how the virus had emerged simultaneously in two geographically distinct areas.

Seroprevalence of antibodies against influenza viruses from 1000 people between the ages of 0 to 90 years of age (100 samples for each decade of life) in the Pittsburgh, PA, USA was measured. One year removed from the outbreak of novel H1N1 influenza into the human population in the Northern Hemisphere and following the emergence of a new H3N2 influenza isolate, sera was collected to determine the hemagglutination-inhibition antibodies against influenza A/H1N1, A/H3N2, and B viruses representative of viruses in the vaccine used for the 2010-2011 influenza season. The seroprevalence of antibodies to influenza virus, A/California/7/2009 (H1N1), increased from the previously reported November 2009 samples and the samples collected at the end of the 2010 influenza season (June 2010) during the 2010-2011 season in all age groups, but people the under the age of 20 had the highest rise in the number of positive samples. The number of individuals positive for H1N1 stayed the same through the entire influenza season. In contrast, there were little to no positive serum samples against the H3N2 virus, A/Perth/16/2009, from samples collected during the 2009-2010 influenza season, however, titers against these viruses rose significantly during the early months of the 2010-2011 season with the highest number of positive samples detected in the very young and very old populations. However, these titers waned by May, 2011 in those over the age of 40. There was a rise in adults to the B/Brisbane/60/2008 influenza virus in adults in samples collected in October, 2010, but these titers quickly declined. The highest titers to B influenza were detected in people between the ages of 10-30 years of age. These findings may have implications for the development of vaccination strategies aiming at the protection against seasonal and/or pandemic influenza virus infection and pre-pandemic preparedness activities.

The Distributed Surveillance Taskforce for Real-time Influenza Burden Tracking and Evaluation (DiSTRIBuTE) project began as a pilot effort initiated by the International Society for Disease Surveillance (ISDS) in autumn 2006 to create a collaborative electronic emergency department (ED) syndromic influenza-like illness (ILI) surveillance network based on existing state and local systems and expertise. DiSTRIBuTE brought together health departments that were interested in: 1) sharing aggregate level data; 2) maintaining jurisdictional control; 3) minimizing barriers to participation; and 4) leveraging the flexibility of local systems to create a dynamic and collaborative surveillance network. This approach was in contrast to the prevailing paradigm for surveillance where record level information was collected, stored and analyzed centrally. The DiSTRIBuTE project was created with a distributed design, where individual level data remained local and only summarized, stratified counts were reported centrally, thus minimizing privacy risks. The project was responsive to federal mandates to improve integration of federal, state, and local biosurveillance capabilities. During the proof of concept phase, 2006 to 2009, ten jurisdictions from across North America sent ISDS on a daily to weekly basis year-round, aggregated data by day, stratified by local ILI syndrome, age-group and region. During this period, data from participating U.S. state or local health departments captured over 13% of all ED visits nationwide. The initiative focused on state and local health department trust, expertise, and control. Morbidity trends observed in DiSTRIBuTE were highly correlated with other influenza surveillance measures. With the emergence of novel A/H1N1 influenza in the spring of 2009, the project was used to support information sharing and ad hoc querying at the state and local level. In the fall of 2009, through a broadly collaborative effort, the project was expanded to enhance electronic ED surveillance nationwide.

We report preliminary results and a summary of a bottom-up approach to identify new, active, nontoxic, small-molecule antivirals designed to have а novel mechanism of action. We employed the procedure to identify 3-mercapto-1,2,4-triazoles derivatives as potential NP inhibitors in silico and subsequently demonstrated the in vitro efficacy of the molecules against various strains of the influenza A virus. The most efficacious compounds were successfully tested in an in vivo influenza challenge experiment.

Objectives
(1) To characterize the epidemiology of H1N1-related hospitalizations in Massachusetts; and (2) to compare characteristics of those hospitalized during periods of seasonal influenza activity and during the H1N1 pandemic.
Methods
Authors applied maximum and minimum criteria to the Massachusetts Hospital Discharge Database to identify H1N1-related hospitalizations. They constructed annual line graphs describing mean frequencies of influenza-like illness(ILI)-related discharges between 2005-2008, and compared these rates to early waves of H1N1 in 2009.
Results
During spring and summer 2009, there were significantly higher rates of ILI-related hospital discharges in Massachusetts compared to 2005-2008. Out of 359,344 total discharges between April 26-September 30,2009, H1N1-related hospitalizations ranged from 601 to 10,967 cases. Minimum criteria confirmed that H1N1 affected a younger population (50% were <18 years), with higher rates among African-Americans (18%) and Hispanics (23%) and higher rates of ICU admission (21%) compared to seasonal influenza (39%, 10%, 14%, and 17% respectively).
Conclusions
This is the first population-based assessment of epidemiological characteristics of hospitalized H1N1 cases in Massachusetts, and it is the first to include all possible hospitalized cases in the analysis. The authors confirm that large administrative data sets can detect hospitalizations for influenza during a pandemic, but estimated case counts vary widely depending on selection criteria used. Maximum criteria overestimated H1N1 activity, and those meeting minimum criteria resemble published accounts of H1N1-related hospitalizations closely.

This study investigated the relationship between school session status and H1N1 influenza prevalence. Weekly means of Influenza-like-Illness (ILI) rates over the period May 1 to October 31, 2009 were compared between areas where schools were and were not in session in the United States. Rates were substantially and significantly higher in areas where schools were in session. This result held separately in spring and fall and was robust to various controls.