Inferring influenza infection attack rate from seroprevalence data.
Seroprevalence survey is the most practical method for accurately estimating infection attack rate (IAR) in an epidemic such as influenza. These studies typically entail selecting an arbitrary titer threshold for seropositivity (e.g. microneutralization [MN] 1∶40) and assuming the probability of seropositivity given infection (infection-seropositivity probability, ISP) is 100% or similar to that among clinical cases. We hypothesize that such conventions are not necessarily robust because different thresholds may result in different IAR estimates and serologic responses of clinical cases may not be representative. To illustrate our hypothesis, we used an age-structured transmission model to fully characterize the transmission dynamics and seroprevalence rises of 2009 influenza pandemic A/H1N1 (pdmH1N1) during its first wave in Hong Kong. We estimated that while 99% of pdmH1N1 infections became MN1∶20 seropositive, only 72%, 62%, 58% and 34% of infections among age 3-12, 13-19, 20-29, 30-59 became MN1∶40 seropositive, which was much lower than the 90%-100% observed among clinical cases. The fitted model was consistent with prevailing consensus on pdmH1N1 transmission characteristics (e.g. initial reproductive number of 1.28 and mean generation time of 2.4 days which were within the consensus range), hence our ISP estimates were consistent with the transmission dynamics and temporal buildup of population-level immunity. IAR estimates in influenza seroprevalence studies are sensitive to seropositivity thresholds and ISP adjustments which in current practice are mostly chosen based on conventions instead of systematic criteria. Our results thus highlighted the need for reexamining conventional practice to develop standards for analyzing influenza serologic data (e.g. real-time assessment of bias in ISP adjustments by evaluating the consistency of IAR across multiple thresholds and with mixture models), especially in the context of pandemics when robustness and comparability of IAR estimates are most needed for informing situational awareness and risk assessment. The same principles are broadly applicable for seroprevalence studies of other infectious disease outbreaks.
Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Joseph T
JT
Wu
Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Kathy
K
Leung
Centre of Influenza Research and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Ranawaka A P M
RA
Perera
Centre of Influenza Research and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Daniel K W
DK
Chu
Hong Kong Red Cross Blood Transfusion Service, Hospital Authority, Hong Kong Special Administrative Region, People's Republic of China.
Cheuk Kwong
CK
Lee
Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Ivan F N
IF
Hung
Hong Kong Red Cross Blood Transfusion Service, Hospital Authority, Hong Kong Special Administrative Region, People's Republic of China.
Che Kit
CK
Lin
Hospital Authority, Hong Kong Special Administrative Region, People's Republic of China; Food and Health Bureau, Government of the Hong Kong Special Administrative Region, Hong Kong Special Administrative Region, People's Republic of China.
Su-Vui
SV
Lo
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Yu-Lung
YL
Lau
Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Gabriel M
GM
Leung
Department of Community Medicine and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Benjamin J
BJ
Cowling
Centre of Influenza Research and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; HKU-Pasteur Research Pole, Centre of Influenza Research and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
J S Malik
JS
Peiris
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D006723:Hong Kong; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D058873:Pandemics; D016036:Seroepidemiologic Studies