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 ser...

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Main Authors: Joseph T Wu, Kathy Leung, Ranawaka A P M Perera, Daniel K W Chu, Cheuk Kwong Lee, Ivan F N Hung, Che Kit Lin, Su-Vui Lo, Yu-Lung Lau, Gabriel M Leung, Benjamin J Cowling, J S Malik Peiris
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-04-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004054&type=printable
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author Joseph T Wu
Kathy Leung
Ranawaka A P M Perera
Daniel K W Chu
Cheuk Kwong Lee
Ivan F N Hung
Che Kit Lin
Su-Vui Lo
Yu-Lung Lau
Gabriel M Leung
Benjamin J Cowling
J S Malik Peiris
author_facet Joseph T Wu
Kathy Leung
Ranawaka A P M Perera
Daniel K W Chu
Cheuk Kwong Lee
Ivan F N Hung
Che Kit Lin
Su-Vui Lo
Yu-Lung Lau
Gabriel M Leung
Benjamin J Cowling
J S Malik Peiris
author_sort Joseph T Wu
collection DOAJ
description 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.
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spelling doaj-art-e576c461398d4ce9aac058d0cded5b5d2025-08-20T03:46:43ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-04-01104e100405410.1371/journal.ppat.1004054Inferring influenza infection attack rate from seroprevalence data.Joseph T WuKathy LeungRanawaka A P M PereraDaniel K W ChuCheuk Kwong LeeIvan F N HungChe Kit LinSu-Vui LoYu-Lung LauGabriel M LeungBenjamin J CowlingJ S Malik PeirisSeroprevalence 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004054&type=printable
spellingShingle Joseph T Wu
Kathy Leung
Ranawaka A P M Perera
Daniel K W Chu
Cheuk Kwong Lee
Ivan F N Hung
Che Kit Lin
Su-Vui Lo
Yu-Lung Lau
Gabriel M Leung
Benjamin J Cowling
J S Malik Peiris
Inferring influenza infection attack rate from seroprevalence data.
PLoS Pathogens
title Inferring influenza infection attack rate from seroprevalence data.
title_full Inferring influenza infection attack rate from seroprevalence data.
title_fullStr Inferring influenza infection attack rate from seroprevalence data.
title_full_unstemmed Inferring influenza infection attack rate from seroprevalence data.
title_short Inferring influenza infection attack rate from seroprevalence data.
title_sort inferring influenza infection attack rate from seroprevalence data
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004054&type=printable
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