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Riley P.,Predictive Science Inc. | Ben-Nun M.,Predictive Science Inc. | Linker J.A.,Predictive Science Inc. | Cost A.A.,Armed Forces Health Surveillance Center | And 5 more authors.
PLoS Computational Biology | Year: 2015

The potential rapid availability of large-scale clinical episode data during the next influenza pandemic suggests an opportunity for increasing the speed with which novel respiratory pathogens can be characterized. Key intervention decisions will be determined by both the transmissibility of the novel strain (measured by the basic reproductive number R0) and its individual-level severity. The 2009 pandemic illustrated that estimating individual-level severity, as described by the proportion pC of infections that result in clinical cases, can remain uncertain for a prolonged period of time. Here, we use 50 distinct US military populations during 2009 as a retrospective cohort to test the hypothesis that real-time encounter data combined with disease dynamic models can be used to bridge this uncertainty gap. Effectively, we estimated the total number of infections in multiple early-affected communities using the model and divided that number by the known number of clinical cases. Joint estimates of severity and transmissibility clustered within a relatively small region of parameter space, with 40 of the 50 populations bounded by: pC, 0.0133–0.150 and R0, 1.09–2.16. These fits were obtained despite widely varying incidence profiles: some with spring waves, some with fall waves and some with both. To illustrate the benefit of specific pairing of rapidly available data and infectious disease models, we simulated a future moderate pandemic strain with pC approximately ×10 that of 2009; the results demonstrating that even before the peak had passed in the first affected population, R0 and pC could be well estimated. This study provides a clear reference in this two-dimensional space against which future novel respiratory pathogens can be rapidly assessed and compared with previous pandemics. © 2015 Wen et al. Source

Webster R.G.,Biomedical Advanced Research and Development Authority BARDA | Webster R.G.,St Jude Childrens Research Hospital | Webby R.J.,St Jude Childrens Research Hospital | Perdue M.,Biomedical Advanced Research and Development Authority BARDA
Birkhauser Advances in Infectious Diseases | Year: 2011

Despite extensive planning for the next influenza pandemic in humans, nature has once again confounded the influenza experts. The emergence and development of an H1N1 pandemic strain while an H1N1 virus was still circulating in humans is an unprecedented event. Here, we examine the emergence of H1N1 influenza viruses in the USA, Europe, and Asia from the natural aquatic bird reservoir through intermediate hosts including pigs and turkeys to humans. There were some remarkable parallel evolutionary developments in the swine influenza viruses in the Americas and in Eurasia. Classical swine influenza virus in the USA emerged either before or immediately after the Spanish influenza virus emerged in humans in 1918. Over the next 50 plus years this swine influenza virus became increasingly attenuated in pigs but occasionally transmitted to humans causing mild clinical infection but did not consistently spread human to human. The remarkable parallel evolution was the introduction of avian influenza virus genes independently in swine influenza viruses in Europe and the USA, with almost simultaneous acquisition of genes from seasonal human influenza. Influenza in pigs in both Eurasia and America became more aggressive necessitating the production of vaccines, and the incidence of transmission of clinical influenza to humans increased. Eventually the different triple reassortants with gene segments from avian, swine, and human influenza viruses in pigs in Europe and America met and mated and developed into the 2009 pandemic H1N1 influenza that is highly transmissible in people, pigs, and turkeys. Whether this occurred in Mexico or in Asia is currently unknown. The failure of the experts was to not recognize the importance of pigs in the evolution and host range transmission of influenza viruses with pandemic potential. © Springer Basel AG 2011. Source

King J.C.,Mission Research | Gao Y.,Biomedical Advanced Research and Development Authority BARDA | Quinn C.P.,Centers for Disease Control and Prevention | Dreier T.M.,Mission Research | And 2 more authors.
Vaccine | Year: 2015

Background/objectives: Anthrax vaccine adsorbed (AVA, BioThrax®) is recommended for post-exposure prophylaxis administration for the US population in response to large-scale Bacillus anthracis spore exposure. However, no information exists on AVA use in children and ethical barriers exist to performing pre-event pediatric AVA studies. A Presidential Ethics Commission proposed a potential pathway for such studies utilizing an age de-escalation process comparing safety and immunogenicity data from 18 to 20 year-olds to older adults and if acceptable proceeding to evaluations in younger adolescents. We conducted exploratory summary re-analyses of existing databases from 18 to 20 year-olds (n=74) compared to adults aged 21 to 29 years (n=243) who participated in four previous US government funded AVA studies. Methods: Data extracted from studies included elicited local injection-site and systemic adverse events (AEs) following AVA doses given subcutaneously at 0, 2, and 4 weeks. Additionally, proportions of subjects with ≥4-fold antibody rises from baseline to post-second and post-third AVA doses (seroresponse) were obtained. Results: Rates of any elicited local AEs were not significantly different between younger and older age groups for local events (79.2% vs. 83.8%, P = 0.120) or systemic events (45.4% vs. 50.5%, P = 0.188). Robust and similar proportions of seroresponses to vaccination were observed in both age groups. Conclusions: AVA was safe and immunogenic in 18 to 20 year-olds compared to 21 to 29 year-olds. These results provide initial information to anthrax and pediatric specialists if AVA studies in adolescents are required. © 2015 Elsevier Ltd. Source

Gessner B.D.,Agence de Medecine Preventive AMP | Brooks W.A.,International Center for Diarrhoeal Disease Research | Brooks W.A.,Johns Hopkins University | Neuzil K.M.,PATH | And 6 more authors.
Vaccine | Year: 2013

There is an increasing focus on influenza in low-resourced areas as a vaccine-preventable cause of severelower respiratory disease in young children, especially among those under two years of age. The extentof the disease burden is unclear: current etiologic studies may underestimate the impact of influenzaif recognized or unrecognized infection occurs some time before severe disease manifestations promptspecimen collection for diagnosis. Because of various methodological challenges, a vaccine probe approach was used to estimate vac-cine preventable disease incidence (VPDI) for Streptococcus pneumoniae and Haemophilus influenzae typeb, particularly for pneumonia outcomes among young children. A similar approach could be used todetermine VPDI for influenza. A highly effective vaccine would facilitate this approach; however, withappropriate design, a less than ideal vaccine also could be used to estimate VPDI. Because influenza vac-cine efficacy against severe disease may be greater than against all symptomatic influenza disease, avaccine probe approach could provide a better measure than etiologic studies of the public health utilityof influenza vaccine. The first 6 months of life is a time of particularly increased influenza risk among young children, andan age group for which current vaccines are not approved. Previous studies have found that maternalinfluenza immunization can reduce acute respiratory infection in the infant during this vulnerable period. Additional randomized, controlled trials are currently underway using a vaccine probe approach to esti-mate VPDI among mothers and their infants following maternal influenza immunization. The WorldHealth Organization now identifies pregnant women as the highest priority target group for influenzavaccination. Should countries implement this strategy, infants age 6-23 months likely would remain atincreased risk; vaccine probe approaches could quantify the public health benefit of immunizing thisgroup. © 2013. Source

Yoo S.S.,U.S. National Institutes of Health | Jorgensen T.J.,Georgetown University | Kennedy A.R.,University of Pennsylvania | Boice Jr. J.D.,Vanderbilt Ingram Cancer Center | And 8 more authors.
Journal of Radiological Protection | Year: 2014

The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (<0.75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident. © 2014 IOP Publishing Ltd. Source

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