Bayesian inference of transmission chains using timing of symptoms, pathogen genomes and contact data
Author(s)
Campbell, Finlay
Cori, Anne
Ferguson, Neil
Jombart, Thibaut
Type
Journal Article
Abstract
There exists significant interest in developing statistical and computational tools for inferring ‘who infected whom’ in an infectious disease outbreak from densely sampled case data, with most recent studies focusing on the analysis of whole genome sequence data. However, genomic data can be poorly informative of transmission events if mutations accumulate too slowly to resolve individual transmission pairs or if there exist multiple pathogens lineages within-host, and there has been little focus on incorporating other types of outbreak data. We present here a methodology that uses contact data for the inference of transmission trees in a statistically rigorous manner, alongside genomic data and temporal data. Contact data is frequently collected in outbreaks of pathogens spread by close contact, including Ebola virus (EBOV), severe acute respiratory syndrome coronavirus (SARS-CoV) and Mycobacterium tuberculosis (TB), and routinely used to reconstruct transmission chains. As an improvement over previous, ad-hoc approaches, we developed a probabilistic model that relates a set of contact data to an underlying transmission tree and integrated this in the outbreaker2 inference framework. By analyzing simulated outbreaks under various contact tracing scenarios, we demonstrate that contact data significantly improves our ability to reconstruct transmission trees, even under realistic limitations on the coverage of the contact tracing effort and the amount of non-infectious mixing between cases. Indeed, contact data is equally or more informative than fully sampled whole genome sequence data in certain scenarios. We then use our method to analyze the early stages of the 2003 SARS outbreak in Singapore and describe the range of transmission scenarios consistent with contact data and genetic sequence in a probabilistic manner for the first time. This simple yet flexible model can easily be incorporated into existing tools for outbreak reconstruction and should permit a better integration of genomic and epidemiological data for inferring transmission chains.
Date Issued
2019-03-29
Date Acceptance
2019-03-04
Citation
PLoS Computational Biology, 2019, 15 (3)
ISSN
1553-734X
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Computational Biology
Volume
15
Issue
3
Copyright Statement
© 2019 Campbell et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Sponsor
National Institute for Health Research
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000463877900067&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
HPRU-2012-10080
MR/R015600/1
MR/K010174/1B
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Mathematical & Computational Biology
Biochemistry & Molecular Biology
ACUTE RESPIRATORY SYNDROME
EBOLA-VIRUS DISEASE
SARS CORONAVIRUS
NOSOCOMIAL OUTBREAK
EPIDEMIC
DYNAMICS
TREES
RISK
DIVERSITY
ORIGINS
Publication Status
Published
Article Number
e1006930
Date Publish Online
2019-03-29