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 (CFR MA) 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 (CFR AR). 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. CFR MA 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 CFR AR to be 0.025%, 16-fold lower than CFR MA. 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.
Bibliographical noteFunding Information:
Financial support. International Network for Strategic Initiatives in Global HIV Trials is funded by the National Institutes of Health (grant UOI-AI068641, SAIC-Frederick HHSN261200800001E). This study was funded through subcontracts (13XS134 and 16Q152) under Leidos Biomedical Corporation’s prime contract (HHSN261200800001E and HHSN261201500003I) with the National Cancer Institute and the National Institute of Allergy and Infectious Diseases. The authors also acknowledge grant support from Danish National Research Foundation (grant 126) and the European Research Commission Horizon 2020 Research and Innovation Framework Program Marie Curie (grant 659437).
© Published by Oxford University Press for the Infectious Diseases Society of America 2018.
- case fatality ratio
- clinical research
- pandemic influenza
- pandemic preparedness