Date of Award

January 2022

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Nathan Grubaugh

Abstract

ABSTRACT West Nile virus (WNV) inhabits a unique position in the infectious disease landscape. It is both the most widespread arbovirus in the world, and yet is one of the least known. WNV is spread by mosquitoes and has high morbidity and mortality in birds, humans are dead-end hosts of the virus but can develop a serious neuroinvasive form of the disease (WNND). The incidence of such cases is on the rise around the world. To explore WNV, we created a comprehensive phylogenetic analysis with all available WNV genomes in genbank database using Nextstrain to identify use cases for increasing WNV genomic sequencing by investigating the following phenomena: lineage specific substitution rates, mutations of interest, and the introduction and spread of WNV into Europe. The substitution rates were 2.89e-4 and 2.62e-4 for European lineages 1a and 2 respectively. Implying that lineage 1a historically has had a greater effective population size than lineage 2. The fact that lineage 1a in Europe historically had fewer confirmed cases while in circulation compared to lineage 2 indicates one of three things; cases were more likely to be missed prior to lineage 2, lineage 1a infects a greater number of bird species, or lineage 2 is more likely to lead to human cases. An investigation of mutation Env:159V from the strain NY99 that was introduced and subsequently spread across the Americas was also identified in Israel 1998 and two years later in Hungary, yet this clade never maintained transmission outside the Americas. Our findings highlight the importance of increasing whole genome sequencing to identify mutations of interest. Lineage 1a and 2 each have one introduction responsible for the majority of sequences and these introductions are characterized by slow spread over the course of many years. While limited by sparse sampling, this indicates that novel introductions that lead to sustained transmission are rare events and spread slowly, taking many years upon introduction to lead to human cases or surveillance is failing to identify cases early. In both scenarios improving surveillance can help public health identify and employ timely prevention measures.

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