Open Collections

McLaughlin, Angela

University of British Columbia

Viral genomes sampled through epidemics illuminate transmission dynamics and evolution, facilitated by bioinformatics, phylogenetics, and genomic epidemiology tools to reconstruct evolutionary trees. Robust inference of large phylogenetic trees depicting viruses’ shared ancestry remains challenging due to computational burden, data biases, model selection, and appropriate use and interpretation of tree-derived metrics. I applied phylogenetics to reconstruct the epidemiological dynamics and evolution of human viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus 1 (HIV-1), in Canada to evaluate the effectiveness of public health interventions in reducing human disease burden. For SARS-CoV-2, I developed a phylogeographic pipeline that reduced sampling bias to reconstruct the timing, origin, destination, and spread of SARS-CoV-2 introductions ancestral to samples in Canada during the first two waves and since the predomination of variants of concern (VOCs) up to early Omicron BA.1 and BA.2. These analyses support that increased stringency of non-pharmaceutical interventions (NPIs) including travel restrictions effectively reduced viral importation rates into Canada and in particular contexts, also case burden. For HIV-1 in British Columbia, we compared growth and drug resistance among phylogenetic clusters, which represent individuals linked through recent outbreaks, to evaluate how effectively and heterogeneously pre-exposure prophylaxis (PrEP) has reduced the effective reproductive number (Re). Newly diagnosed PrEP users were more likely than non-PrEP users to join clusters and were at increased risk of carrying baseline M184IV mutation, conferring drug resistance to nucleoside reverse transcriptase inhibitor (NRTI) drugs commonly prescribed in combined antiretroviral therapies. Widespread PrEP availability since 2018 in BC has been successful, with an associated reduction of Re in the gay, bisexual, and other men who have sex with men (GBM) community, but several GBM-predominant clusters had no reduction in Re since PrEP, highlighting groups who could benefit from prioritized treatment and prevention resources. This body of work contributes novel applications of phylogenetics to reconstruct viral epidemics, including subsampling, bootstrapping, and counterfactual stochastic modeling, which were interpreted within the context of interventions, informing infectious disease dynamics and policy.

Text

2024-08-28

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89061

Bioinformatics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/