Influenza A viruses (IAV) are significant human pathogens causing yearly epidemics and occasional pandemics. Past pandemics have resulted in significant morbidity and mortality. The 1918 influenza pandemic was thought to have resulted in the death of at least 675,000 people in the U.S. and 40 million people worldwide. Pandemics in 1957 and 1968, while less severe, were also of major public health importance. A novel influenza A virus of swine origin became pandemic in 2009, causing the first pandemic in 41 years. In addition, annual epidemic influenza cases are also very significant resulting in up to 49,000 deaths in the U.S. annually. Clinical natural history studies to compare natural influenza virus infections in immunocompromised, non-immunocompromised, and other high-risk populations, including pregnant women, are important to better treat and prevent influenza virus-infected patients. We plan to ultimately recruit up to 1000 patients with influenza virus infection. Recruitment occurred in both inpatient and outpatient settings at multiple sites including the NIH Clinical Center, Suburban Hospital and the Washington Hospital Center. Careful clinical evaluation, analysis of viruses collected from patients, and studies of the immune response of the patients is being performed. An ongoing effort is continuing to analyze the data collected over the past 4 years of this study and a report on these data is planned within the next 6 months. As an adjunct to the natural history studies, the first human volunteer influenza virus challenge study to be performed in the U.S. in over a decade began this past year using a 2009 influenza A/H1N1 virus under an FDA-approved IND. A healthy volunteer screening study began at the Clinical Center to identify patients who will qualify and be available for these challenge studies in the upcoming months. The initial challenge study protocol, a dose finding study, has been evaluated and data analysis is currently underway. Additional viral seed stocks of recent H3N2 and H1N1 viruses are being prepared.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2013
Total Cost
$1,347,530
Indirect Cost
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State
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Hunsberger, Sally; Memoli, Matthew J (2018) Efficacy Analysis in Healthy-Volunteer Influenza Challenge Trials: Intention To Treat. Antimicrob Agents Chemother 62:
Danis, Marion; Doernberg, Sam; Memoli, Matthew et al. (2018) Best to Exclude but Pay. Am J Bioeth 18:87-88
Powers 3rd, John H; Bacci, Elizabeth D; Leidy, Nancy K et al. (2018) Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI). PLoS One 13:e0194180
Park, Jae-Keun; Han, Alison; Czajkowski, Lindsay et al. (2018) Evaluation of Preexisting Anti-Hemagglutinin Stalk Antibody as a Correlate of Protection in a Healthy Volunteer Challenge with Influenza A/H1N1pdm Virus. MBio 9:
Powers 3rd, John H; Bacci, Elizabeth D; Guerrero, M Lourdes et al. (2018) Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients. Value Health 21:210-218
Wang, Taia T; Sewatanon, Jaturong; Memoli, Matthew J et al. (2017) IgG antibodies to dengue enhanced for Fc?RIIIA binding determine disease severity. Science 355:395-398
Kash, John C; Walters, Kathie-Anne; Kindrachuk, Jason et al. (2017) Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease. Sci Transl Med 9:
Memoli, Matthew J; Shaw, Pamela A; Han, Alison et al. (2016) Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model. MBio 7:e00417-16
Memoli, Matthew J (2015) Critically ill patients with H7N9: new virus, old challenges*. Crit Care Med 43:487-8
Memoli, Matthew J; Czajkowski, Lindsay; Reed, Susan et al. (2015) Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Clin Infect Dis 60:693-702

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