Dataset Information

Application of an Individual-Based Transmission Hazard Model for Estimation of Influenza Vaccine Effectiveness in a Household Cohort.

ABSTRACT: Household cohort studies are an important design for the study of respiratory virus transmission. Inferences from these studies can be improved through the use of mechanistic models to account for household structure and risk as an alternative to traditional regression models. We adapted a previously described individual-based transmission hazard (TH) model and assessed its utility for analyzing data from a household cohort maintained in part for study of influenza vaccine effectiveness (VE). Households with ?4 individuals, including ?2 children <18 years of age, were enrolled and followed during the 2010-2011 influenza season. VE was estimated in both TH and Cox proportional hazards (PH) models. For each individual, TH models estimated hazards of infection from the community and each infected household contact. Influenza A(H3N2) infection was laboratory-confirmed in 58 (4%) subjects. VE estimates from both models were similarly low overall (Cox PH: 20%, 95% confidence interval: -57, 59; TH: 27%, 95% credible interval: -23, 58) and highest for children <9 years of age (Cox PH: 40%, 95% confidence interval: -49, 76; TH: 52%, 95% credible interval: 7, 75). VE estimates were robust to model choice, although the ability of the TH model to accurately describe transmission of influenza presents continued opportunity for analyses.

SUBMITTER: Petrie JG

PROVIDER: S-EPMC5860432 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Application of an Individual-Based Transmission Hazard Model for Estimation of Influenza Vaccine Effectiveness in a Household Cohort.

Petrie Joshua G JG Eisenberg Marisa C MC Ng Sophia S Malosh Ryan E RE Lee Kyu Han KH Ohmit Suzanne E SE Monto Arnold S AS

American journal of epidemiology 20171201 12

Household cohort studies are an important design for the study of respiratory virus transmission. Inferences from these studies can be improved through the use of mechanistic models to account for household structure and risk as an alternative to traditional regression models. We adapted a previously described individual-based transmission hazard (TH) model and assessed its utility for analyzing data from a household cohort maintained in part for study of influenza vaccine effectiveness (VE). Ho ...[more]

PMID: 28605429

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Project description:BackgroundThe ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated the effectiveness of Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford AstraZeneca adenovirus vector vaccine (ChAdOx1) vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England.MethodsHouseholds were recruited based on adult purported index cases testing positive after reverse transcription-quantitative (RT-q)PCR testing of oral-nasal swabs. Purported index cases and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment and a subset of the PCR-positive swabs underwent genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant.ResultsBetween 2 February 2021 and 10 September 2021, 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained, of whom 113 (41%) became PCR positive. Delta lineages had 1.53 times the risk (95% Credible Interval: 1.04 - 2.20) of transmission than Alpha; contacts older than 18 years old were 1.48 (1.20 - 1.91) and 1.02 (0.93 - 1.16) times more likely to acquire an Alpha or Delta infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 36% (-1%, 66%) and 49% (18%, 73%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 69% (9%, 95%) vs. 18% (-11%, 59%), respectively, for BNT162b2 and 24% (-41%, 72%) vs. 9% (-15%, 42%), respectively, for ChAdOx1.ConclusionsBNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting, although their protection against infection within this setting is low.

Project description:The bottleneck governing infectious disease transmission describes the size of the pathogen population transferred from the donor to the recipient host. Accurate quantification of the bottleneck size is particularly important for rapidly evolving pathogens such as influenza virus, as narrow bottlenecks reduce the amount of transferred viral genetic diversity and, thus, may decrease the rate of viral adaptation. Previous studies have estimated bottleneck sizes governing viral transmission by using statistical analyses of variants identified in pathogen sequencing data. These analyses, however, did not account for variant calling thresholds and stochastic viral replication dynamics within recipient hosts. Because these factors can skew bottleneck size estimates, we introduce a new method for inferring bottleneck sizes that accounts for these factors. Through the use of a simulated data set, we first show that our method, based on beta-binomial sampling, accurately recovers transmission bottleneck sizes, whereas other methods fail to do so. We then apply our method to a data set of influenza A virus (IAV) infections for which viral deep-sequencing data from transmission pairs are available. We find that the IAV transmission bottleneck size estimates in this study are highly variable across transmission pairs, while the mean bottleneck size of 196 virions is consistent with a previous estimate for this data set. Furthermore, regression analysis shows a positive association between estimated bottleneck size and donor infection severity, as measured by temperature. These results support findings from experimental transmission studies showing that bottleneck sizes across transmission events can be variable and influenced in part by epidemiological factors.IMPORTANCE The transmission bottleneck size describes the size of the pathogen population transferred from the donor to the recipient host and may affect the rate of pathogen adaptation within host populations. Recent advances in sequencing technology have enabled bottleneck size estimation from pathogen genetic data, although there is not yet a consistency in the statistical methods used. Here, we introduce a new approach to infer the bottleneck size that accounts for variant identification protocols and noise during pathogen replication. We show that failing to account for these factors leads to an underestimation of bottleneck sizes. We apply this method to an existing data set of human influenza virus infections, showing that transmission is governed by a loose, but highly variable, transmission bottleneck whose size is positively associated with the severity of infection of the donor. Beyond advancing our understanding of influenza virus transmission, we hope that this work will provide a standardized statistical approach for bottleneck size estimation for viral pathogens.

Dataset Information

Application of an Individual-Based Transmission Hazard Model for Estimation of Influenza Vaccine Effectiveness in a Household Cohort.

Publications

Application of an Individual-Based Transmission Hazard Model for Estimation of Influenza Vaccine Effectiveness in a Household Cohort.

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