Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.

<h4>Background</h4>In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimat...

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Main Authors: Joseph T Wu, Andrew Ho, Edward S K Ma, Cheuk Kwong Lee, Daniel K W Chu, Po-Lai Ho, Ivan F N Hung, Lai Ming Ho, Che Kit Lin, Thomas Tsang, 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) 2011-10-01
Series:PLoS Medicine
Online Access:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001103&type=printable
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author Joseph T Wu
Andrew Ho
Edward S K Ma
Cheuk Kwong Lee
Daniel K W Chu
Po-Lai Ho
Ivan F N Hung
Lai Ming Ho
Che Kit Lin
Thomas Tsang
Su-Vui Lo
Yu-Lung Lau
Gabriel M Leung
Benjamin J Cowling
J S Malik Peiris
author_facet Joseph T Wu
Andrew Ho
Edward S K Ma
Cheuk Kwong Lee
Daniel K W Chu
Po-Lai Ho
Ivan F N Hung
Lai Ming Ho
Che Kit Lin
Thomas Tsang
Su-Vui Lo
Yu-Lung Lau
Gabriel M Leung
Benjamin J Cowling
J S Malik Peiris
author_sort Joseph T Wu
collection DOAJ
description <h4>Background</h4>In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimates of infection attack rate (IAR) and severity.<h4>Methods and findings</h4>We tested 14,766 sera collected during the first wave of the 2009 pandemic in Hong Kong using viral microneutralization. We estimated IAR and infection-hospitalization probability (IHP) from the serial cross-sectional serologic data and hospitalization data. Had our serologic data been available weekly in real time, we would have obtained reliable IHP estimates 1 wk after, 1-2 wk before, and 3 wk after epidemic peak for individuals aged 5-14 y, 15-29 y, and 30-59 y. The ratio of IAR to pre-existing seroprevalence, which decreased with age, was a major determinant for the timeliness of reliable estimates. If we began sero-surveillance 3 wk after community transmission was confirmed, with 150, 350, and 500 specimens per week for individuals aged 5-14 y, 15-19 y, and 20-29 y, respectively, we would have obtained reliable IHP estimates for these age groups 4 wk before the peak. For 30-59 y olds, even 800 specimens per week would not have generated reliable estimates until the peak because the ratio of IAR to pre-existing seroprevalence for this age group was low. The performance of serial cross-sectional sero-surveillance substantially deteriorates if test specificity is not near 100% or pre-existing seroprevalence is not near zero. These potential limitations could be mitigated by choosing a higher titer cutoff for seropositivity. If the epidemic doubling time is longer than 6 d, then serial cross-sectional sero-surveillance with 300 specimens per week would yield reliable estimates when IAR reaches around 6%-10%.<h4>Conclusions</h4>Serial cross-sectional serologic data together with clinical surveillance data can allow reliable real-time estimates of IAR and severity in an emerging pandemic. Sero-surveillance for pandemics should be considered.
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spelling doaj-art-243f6596bfe0419a9b653e2cba4878332025-08-20T03:10:04ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762011-10-01810e100110310.1371/journal.pmed.1001103Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.Joseph T WuAndrew HoEdward S K MaCheuk Kwong LeeDaniel K W ChuPo-Lai HoIvan F N HungLai Ming HoChe Kit LinThomas TsangSu-Vui LoYu-Lung LauGabriel M LeungBenjamin J CowlingJ S Malik Peiris<h4>Background</h4>In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimates of infection attack rate (IAR) and severity.<h4>Methods and findings</h4>We tested 14,766 sera collected during the first wave of the 2009 pandemic in Hong Kong using viral microneutralization. We estimated IAR and infection-hospitalization probability (IHP) from the serial cross-sectional serologic data and hospitalization data. Had our serologic data been available weekly in real time, we would have obtained reliable IHP estimates 1 wk after, 1-2 wk before, and 3 wk after epidemic peak for individuals aged 5-14 y, 15-29 y, and 30-59 y. The ratio of IAR to pre-existing seroprevalence, which decreased with age, was a major determinant for the timeliness of reliable estimates. If we began sero-surveillance 3 wk after community transmission was confirmed, with 150, 350, and 500 specimens per week for individuals aged 5-14 y, 15-19 y, and 20-29 y, respectively, we would have obtained reliable IHP estimates for these age groups 4 wk before the peak. For 30-59 y olds, even 800 specimens per week would not have generated reliable estimates until the peak because the ratio of IAR to pre-existing seroprevalence for this age group was low. The performance of serial cross-sectional sero-surveillance substantially deteriorates if test specificity is not near 100% or pre-existing seroprevalence is not near zero. These potential limitations could be mitigated by choosing a higher titer cutoff for seropositivity. If the epidemic doubling time is longer than 6 d, then serial cross-sectional sero-surveillance with 300 specimens per week would yield reliable estimates when IAR reaches around 6%-10%.<h4>Conclusions</h4>Serial cross-sectional serologic data together with clinical surveillance data can allow reliable real-time estimates of IAR and severity in an emerging pandemic. Sero-surveillance for pandemics should be considered.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001103&type=printable
spellingShingle Joseph T Wu
Andrew Ho
Edward S K Ma
Cheuk Kwong Lee
Daniel K W Chu
Po-Lai Ho
Ivan F N Hung
Lai Ming Ho
Che Kit Lin
Thomas Tsang
Su-Vui Lo
Yu-Lung Lau
Gabriel M Leung
Benjamin J Cowling
J S Malik Peiris
Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.
PLoS Medicine
title Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.
title_full Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.
title_fullStr Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.
title_full_unstemmed Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.
title_short Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.
title_sort estimating infection attack rates and severity in real time during an influenza pandemic analysis of serial cross sectional serologic surveillance data
url https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1001103&type=printable
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