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Clin Infect Dis. 2018 Jul 18;67(3):341-349. doi: 10.1093/cid/ciy088.

Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic.

Collaborators (227)

Munroe D, Rappoport C, Schwarze S, Aagaard B, Adzic D, Grarup J, Herrero P, Jansson P, Jakobsen ML, Jensen B, Jensen KB, Juncher H, Kjær J, Lundgren J, Lopez P, Mocroft A, Pearson M, Portas B, Sabin C, Tillmann K, Babiker A, Braimah N, Collaco-Moraes Y, Hudson F, Kummeling I, Pacciarini F, Paton N, George M, Harrison M, Herman K, Krum E, Larson G, Nelson R, Quan K, Quan SF, Reilly C, Schultz T, Thompson G, Wyman N, Avihingsanon A, Cassar L, Charoentonpuban K, Emery S, Laohajinda K, Jupimai T, Lanusse I, Moricz A, Otegui I, Ruxrungtham K, Robson R, Finley E, Gordin F, Sanchez A, Vjecha M, Baxter J, Brown S, Ghedin E, Halpin R, Hoover M, Metcalf JA, Gubareva L, Hancock K, Katz J, Klimov A, Shaw M, Barcan L, Corral JA, David DO, Laplume HE, Lasala MB, Lopardo GD, Losso MH, Lupo S, Warley E, Bloch M, Dwyer DE, Moore R, Pett SL, Roth N, Soo TM, Vlahakis E, Burgmann H, Clumeck N, De Wit S, Florence E, Kabeya K, Weckx J, Perez C, Wolff MJ, Gerstoft J, Lundgren JD, Østergaard L, Zilmer K, Bogner JR, Brockmeyer NH, Faetkenheuer G, Klinker H, Plettenberg A, Rockstroh J, Stephan C, Antoniadou A, Koratzanis G, Koulouris N, Polixronopoulos V, Sambatakou H, Vasilopoulos N, Caplinskas S, La Rosa A, Mendo F, Salazar R, Valencia J, Bakowska E, Horban A, Knysz B, Antunes F, Doroana M, Padayatchi N, Dalmau D, Fernandez-Cruz E, Gatell JM, Sanz JS, Soriano V, Chetchotisakd P, Ruxrungtham K, Suwanpimolkul G, Leen CLS, Cohen C, Cohn DL, DeHovitz JA, El-Sadr W, Glesby M, Gordin FM, Hodder S, Markowitz N, Novak RM, Schooley R, Simon GL, Tedaldi EM, Temesgen Z, Timpone J, Uslan DZ, Wade BH, Barcan L, Corral JA, David DO, Laplume HE, Lasala MB, Lopardo GD, Losso MH, Warley E, Dwyer DE, Elliott J, Konecny P, McBride J, Pett SL, Burgmann H, Clumeck N, De Wit S, Jorens P, Kabeya K, Wolff MJ, Wu TC, Gerstoft J, Mathiesen L, Nielsen H, Østergaard L, Pedersen SS, Bergmann F, Bogner JR, Brockmeyer NH, Faetkenheuer G, Klinker H, Rockstroh J, Stephan C, Antoniadou A, Koratzanis G, Koulouris N, Polixronopoulos V, Sambatakou H, Vasilopoulos N, Maagaard A, Mendo F, Salazar R, Bakowska E, Horban A, Padayatchi N, Dalmau D, Estrada V, Fernandez-Cruz E, Freud HK, Blazquez Garrido RM, Gatell JM, Moreno JS, Pano-Pardo JR, Sanz JS, Soriano V, Chetchotisakd P, Ruxrungtham K, Suwanpimolkul G, Angus BJ, Chadwick DR, Dockrell D, Leen CLS, Newport M, Wilkins E, Iii HA, Baker JV, Cohn DL, DeHovitz JA, El-Sadr W, Freiberg MS, Gordin FM, Gulick R, Gurka D, Hodder S, Markowitz N, Novak RM, Paez A, Patil N, Reboli A, Sands M, Schooley R, Simon GL, Temesgen Z, Timpone J, Uslan DZ, Wade BH.

Author information

1
Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark.
2
Department of Science and Environment, Roskilde University, Denmark.
3
National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
4
Sage Analytica, Bethesda, Maryland.
5
Division of Biostatistics, University of Minnesota, Minneapolis.
6
University College, London, United Kingdom.
7
Medical Research Council Clinical Trials Unit and Clinical Research Group, University College, London, United Kingdom.
8
The Kirby Institute, University of New South Wales, Australia.
9
Centre for Infectious Diseases and Microbiology Laboratory Services, Institute for Clinical Pathology and Medical Research, Westmead Hospital and University of Sydney, Australia.
10
Minnesota Department of Health, St. Paul.
11
Hospital J.M. Ramos Mejía, Buenos Aires, Argentina.
12
Weill Cornell Medical College, New York, New York.
13
Testumed Vereniging zonder winstoogmerk, Tessenderlo, Belgium.

Abstract

Background:

Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response.

Methods:

We estimated the CFR of medically attended influenza (CFRMA) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009-2011) and post-pandemic (2012-2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFRAR).

Results:

During the pandemic period, 5.0% (3.1%-6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%-12.6%) died. CFRMA for pH1N1 was 0.4% (0.2%-0.6%) in the pandemic period 2009-2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012-2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFRAR to be 0.025%, 16-fold lower than CFRMA.

Conclusions:

Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity.

Clinical Trials Registration:

NCT01056354 and NCT010561.

PMID:
29746631
PMCID:
PMC6248856
[Available on 2019-08-01]
DOI:
10.1093/cid/ciy088

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