Population Genomics of Francisella tularensis subsp. holarctica and its Implication on the Eco-Epidemiology of Tularemia in Switzerland

Abstract

Whole genome sequencing (WGS) methods provide new possibilities in the field of molecular epidemiology. This is particularly true for monomorphic organisms where the discriminatory power of traditional methods (e.g., restriction enzyme length polymorphism typing, multi locus sequence typing etc.) is inadequate to elucidate complex disease transmission patterns, as well as resolving the phylogeny at high resolution on a micro-geographic scale. In this study, we present insights into the population structure of Francisella tularensis subsp. holarctica, the causative agent of tularemia in Switzerland. A total of 59 Fth isolates were obtained from castor bean ticks (Ixodes ricinus), animals and humans and a high resolution phylogeny was inferred using WGS methods. The majority of the Fth population in Switzerland belongs to the west European B.11 clade and shows an extraordinary genetic diversity underlining the old evolutionary history of the pathogen in the alpine region. Moreover, a new B.11 subclade was identified which was not described so far. The combined analysis of the epidemiological data of human tularemia cases with the whole genome sequences of the 59 isolates provide evidence that ticks play a pivotal role in transmitting Fth to humans and other vertebrates in Switzerland. This is further underlined by the correlation of disease risk estimates with climatic and ecological factors influencing the survival of ticks.

Phylogeography and Genetic Diversity of Francisella tularensis subsp. holarctica in France (1947–2018)

“…flies and mosquitoes) also play an important role but, at least in France, this role in tularemia transmission has been poorly studied. A recent study in Switzerland, where ticks were found to be the main cause of infection in humans (Lyko and Chuard, 2013), suggested that strains of clade B.45 were better adapted than other clades to arthropods vectors, as clade B.46 and the newly identified B.11 subclades were isolated only in humans and mammals (Wittwer et al, 2018). However, in France, tick bites represent only around 10% of tularemia cases (Maurin et al, 2011) andMichelet et al (2014) suggested that the risk of acquiring tularemia from ticks -Ixodes ricinus at least -was negligible.…”

“…Clade B.6 is found in Western Europe and North America, whereas clade B.12 has been isolated mainly in Eastern Europe, and groups together erythromycin-resistant strains (Vogler et al, 2009). In Germany, Switzerland, Sweden, Norway and Finland, both of these major clades have been detected (Karlsson et al, 2013;Müller et al, 2013;Origgi et al, 2014;Afset et al, 2015;Sissonen et al, 2015;Wittwer et al, 2018). Clade B.16 correlates with biovar japonica, isolated in Japan and recently in Turkey (Ulu-Kilic et al, 2013), China (Wang et al, 2014), and Australia (Eden et al, 2017).…”

Case of the month: What’s your diagnosis?

“…Catalase and oxidase reaction tested negative. ural reservoir and ticks as vectors 10 . The species F. tularensis comprises two subspecies, namely tularensis (Type A strain) and holarctica (Type B strain) 5 .…”

“…The incidence of tularemia in humans in Switzerland increased significantly from seven cases in 2004 to 131 cases in 2017 according to the annual case numbers of the Swiss Federal Office for Public Health and is now considered a reemerging disease with an increasing veterinary public health relevance 4,10 . An epidemiological study of 276 human tularemia cases in Switzerland investigated causative risk factors for disease occurrence.…”

“…An epidemiological study of 276 human tularemia cases in Switzerland investigated causative risk factors for disease occurrence. 57% of the patients reported insect or arthropod bites (33% tick-bite, 24% insects) and 22% had contact with wild animals prior to contracting tularemia 2,10 . Recent studies in Northern Europe and Austria evaluated whether companion animals serve as a source of infection for humans, after contact to tularemia positive wild animals or contaminated environment.…”