The 2012-13 influenza season had an unusually early and severe start in the US, succeeding the record mild 2011-12 influenza season, which occurred during the fourth warmest winter on record. Our analysis of climate and past US influenza epidemic seasons between 1997-98 to present indicates that warm winters tend to be followed by severe epidemics with early onset, and that these patterns are seen for both influenza A and B. We posit that fewer people are infected with influenza during warm winters, thereby leaving an unnaturally large fraction of susceptible individuals in the population going into the next season, which can lead to early and severe epidemics.

In the event of continued global warming, warm winters such as that of 2011-12 are expected to occur more frequently. Our results thus suggest that expedited manufacture and distribution of influenza vaccines after mild winters has the potential to mitigate the severity of future influenza epidemics.

Seasonal influenza has considerable impact around the world, both economically and in mortality among risk groups. The long term patterns of disease are hard to capture with simple models, while the interplay of epidemiological processes with antigenic evolution makes detailed modelling difficult and computationally intensive. We identify a number of characteristic features of flu incidence time series in temperate regions, including ranges of annual attack rates and outbreak durations. We construct pseudo-likelihoods to capture these characteristic features and examine the ability of a collection of simple models to reproduce them under seasonal variation in transmission. Results indicate that an age-structured model with non-random mixing and co-circulating strains are both required to match time series data. The extent of matching behaviour also serves to define informative ranges for parameters governing essential dynamics. Our work gives estimates of the seasonal peak basic reproduction, R₀, in the range 1.7-2.1, with the degree of seasonal variation having limited impact of these estimates. We find that it is only really possible to estimate a lower bound on the degree of seasonal variation in influenza transmissibility, namely that transmissibility in the low transmission season may be only 5-10% less than the peak value. These results give some insight into the extent to which transmissibility of the H1N1pdm pandemic virus may increase in Northern Hemisphere temperate countries in winter 2009. We find that the timescale for waning of immunity to current circulating seasonal influenza strain is between 4 and 8 years, consistent with studies of the antigenic variation of influenza, and that inter-subtype cross-immunity is restricted to low levels.

BACKGROUND: In April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents.

METHODS AND FINDINGS: Anonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n= 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n=100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10-19 years having the highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%). The baseline seroprevalence among control samples from 18-24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%.

CONCLUSIONS: After the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children.

Background: As Pandemic (H1N1) 2009 influenza spreads around the globe, it strikes school-age children more often than adults. Although there is some evidence of pre-existing immunity among older adults, this alone may not explain the significant gap in age-specific infection rates.

Methods & Findings: Based on a retrospective analysis of pandemic strains of influenza from the last century, we show that school-age children typically experience the highest attack rates in primarily naive populations, with the burden shifting to adults during the subsequent season. Using a parsimonious network-based mathematical model which incorporates the changing distribution of contacts in the susceptible population, we demonstrate that new pandemic strains of influenza are expected to shift the epidemiological landscape in exactly this way.

Conclusions: Our results provide a simple demographic explanation for the age bias observed for H1N1/09 attack rates, and a prediction that this bias will shift in coming months. These results also have significant implications for the allocation of public health resources including vaccine distribution policies.

Background: Accurate measures of the severity of pandemic influenza A/H1N1 (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely.

Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data: medically attended cases in Milwaukee or self-reported influenza-like illness in New York, were used to estimate ratios of symptomatic cases:hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic cases that died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated sCFR of 0.048% (95% credible interval, CI 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-9x lower. sCFR and sCIR appear to be highest in persons 18 and older, and lowest in children 5-17. sCHR appears to be lowest in persons 5-17; our data were too sparse to allow us to determine the group in which it was the highest.

Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with greatest impact in young children and non-elderly adults. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the proportion infected or symptomatic were lower.

The 2009 swine-origin strain of Influenza A H1N1 has spread to nearly all parts of the world, with 175 countries reporting confirmed cases thus far. Consistent with seasonal flu outbreaks, the current pandemic strain has shown rapid dispersal, with multiple examples of introduction into different geographic regions. Here we use an automated pipeline to collect data for analysis in the geospatial package GenGIS, which allows the geographic and temporal tracking of new sequence types and polymorphisms. Using this approach, we examine a pair of amino acid changes in the neuraminidase protein that are implicated in antibody recognition, and exhibit global dispersal with little or no geographic structure.

In late June 2009, we implemented for public hospitals of Marseille Point Of Care strategy for rapid diagnosis of novel A/H1N1 influenza virus. During two months, we have tested more than 900 specimens in both Point Of Care laboratories. We believe that implementation of Point of Care strategy for the largest number of suspects cases may improve quality of patients care and our knowledge of the epidemiology of the pandemic.

Here we use lessons from past influenza pandemics and recent information about the H1N1pdm pandemic to discuss variations in H1N1pdm disease burden with age, underlying risk factors, and geography.

In the early phase of the 2009 A (H1N1) pandemic a marked increase in severity and a shift in the age distribution toward younger persons was found, with higher severity reported in patients with pre-existing medical conditions and pregnant women. Consistent with previous pandemics, the age and clinical history of the patients play a critical role in the morbidity and mortality associated with the pandemic virus. This is the first influenza pandemic in the information era, where enormous amounts of information will be available from the pathogen and the patient. Recent advances in molecular techniques have provided an enormous amount of information about pathogens in near real time and at relatively low cost. Electronic Health Records (EHRs) provide another enormously rich set of information about patients, which include patient preconditions, previous exposures, immunization history, presenting complaints, duration and severity of illness, treatment history, and geographic location. An infectious disease is a complex interplay between host and pathogen. The morbidity and mortality of a virus depend on the virus, the patient, and the environment. To evaluate and understand the severity of the pandemic virus and to identify the populations at risk of mild or severe, life-threatening illness, it is compulsory to integrate viral and patient information in a fast and accurate way. Both advances in biomedical informatics with the creation of EHRs and molecular techniques provide the framework to achieve these aims.

Previous human influenza pandemics were the results of emerging viruses from non-human reservoirs, with at least two caused by strains of mixed human and avian origin. Also, many cases of swine influenza viruses have reportedly infected humans, including the recent human H1N1 strain, isolated in Mexico and the United States. Pigs are documented to get infected with human, avian, and swine viruses and allow productive replication, thus it has been conjectured that they are the “mixing vessel” that create reassortant strains, causing the human pandemics. In this paper, we apply several statistical techniques to an ensemble of publicly available swine viruses to study the reassortment phenomena. The reassortment patterns in swine viruses confirm previous results found in human viruses that the glycoprotein coding segments reassort most often. Moreover, one of the polymerase segments (PB1), reassorted in the strains responsible for the last two human pandemics of 1957 and 1968, also reassorts frequently.

We consider the net benefits of predispensing antivirals to high-risk individuals during an influenza pandemic, where the measure of the benefit is the number of severe outcomes (such as deaths or hospitalizations) prevented by antivirals in the whole population. One potential benefit of predispensing is that individuals to whom antivirals have been predispensed may be able to initiate treatment earlier than if they had to wait to obtain and fill a prescription, reducing their risk of progression to severe disease. If this benefit exceeds the side effects of misuse for the category of individuals to whom antivirals were predispensed, and if antiviral supply exceeds overall population demand (which appears relevant for several countries including US in the current H1N1 pandemic), predispensing a quantity of antivirals not exceeding the difference between supply and demand is always beneficial. In this paper we consider the net benefits of predispensing antivirals under various scenarios, including demand exceeding supply, and derive mathematical conditions under which antiviral predispensing is advantageous on balance. For individuals whose relative risk of severe outcome is high enough, such as immunosuppressed individuals (particularly children) and possibly individuals with neurological disorders, predispensing is always beneficial at a given level of antiviral stockpile with modest assumptions on the relative benefit of early treatment by a predispensed course, regardless of the overall population demand for antivirals during the course of an epidemic. Making additional assumptions on either the overall population demand for antivirals (which appear relevant in the current situation) or on the relative benefit of predispensing would make predispensing net beneficial with inclusion of a larger number of persons such as pregnant women and morbidly obese adults.

In this modeling work, we explore the effectiveness of various age-targeted vaccination strategies to mitigate hospitalization and mortality from pandemic influenza, assuming limited vaccine supplies. We propose a novel adaptive vaccination strategy in which vaccination is initiated during the outbreak and priority groups are identified based on real-time epidemiological data monitoring age-specific risk of hospitalization and death. We apply this strategy to detailed epidemiological and demographic data collected during the recent swine A/H1N1 outbreak in Mexico. We show that the adaptive strategy targeting age groups 6-59 years is the most effective in reducing hospitalizations and deaths, as compared with a more traditional strategy used in the control of seasonal influenza and targeting children under 5 and seniors over 65. Results are robust to a number of assumptions and could provide guidance to many nations facing a recrudescence of A/H1N1v pandemic activity in the fall and likely vaccine shortages.

Using the guinea pig model, we have previously shown that the aerosol transmission of a seasonal human influenza virus is blocked by humid (80% relative humidity) or warm (30°C) ambient conditions. In contrast, we found that transmission by a contact route proceeded at high efficiency despite increased temperature or humidity. Based on these findings, and the observed seasonal behavior of influenza viruses in various regions of the world, we hypothesize herein that the predominant mode of influenza virus transmission differs in temperate and tropical climates. Specifically, we predict that aerosol transmission predominates during the winter season in temperate regions, while contact is the major mode of spread in the tropics. With this idea in mind, possible explanations for the current summer-time spread of swine-origin influenza viruses are discussed.