Globetrotting strangles: the unbridled national and international transmission of Streptococcus equi between horses

Abstract

The equine disease strangles, which is characterized by the formation of abscesses in the lymph nodes of the head and neck, is one of the most frequently diagnosed infectious diseases of horses around the world. The causal agent, Streptococcus equi subspecies equi, establishes a persistent infection in approximately 10 % of animals that recover from the acute disease. Such 'carrier' animals appear healthy and are rarely identified during routine veterinary examinations pre-purchase or transit, but can transmit S. equi to naïve animals initiating new episodes of disease. Here, we report the analysis and visualization of phylogenomic and epidemiological data for 670 isolates of S. equi recovered from 19 different countries using a new core-genome multilocus sequence typing (cgMLST) web bioresource. Genetic relationships among all 670 S. equi isolates were determined at high resolution, revealing national and international transmission events that drive this endemic disease in horse populations throughout the world. Our data argue for the recognition of the international importance of strangles by the Office International des Épizooties to highlight the health, welfare and economic cost of this disease. The Pathogenwatch cgMLST web bioresource described herein is available for tailored genomic analysis of populations of S. equi and its close relative S. equi subspecies zooepidemicus that are recovered from horses and other animals, including humans, throughout the world. This article contains data hosted by Microreact.

Keywords: Streptococcus equi; genome diversity; pandemic; strangles; transmission.

Fig. 1.

A global picture of S. equi diversity visualized in Microreact. Coloured circles indicate the country from which the isolates originated, as illustrated in the key. (a) World map depicting the country of origin of the 670  S . equi isolates. (b) Midpoint-rooted phylogenetic reconstruction of the S. equi population. The dendrogram was reconstructed from pairwise cgMLST scores using the ape package [25]. The resulting tree was midpoint rooted using the phangorn package [26]. The scale bar relates to horizontal branch lengths and indicates the number of cgSNPs that are proposed to have occurred on the vertical branches. The six genetically distinct BAPS clusters and six multilocus STs are indicated on the coloured metadata bars and associated key. (c) Timeline of the collection from 1955 to 2017.

Fig. 2.

BAPS-1 illustrates international transmission events between the USA, UAE, Israel, Japan, Canada and the UK. Midpoint-rooted phylogenetic reconstruction of the S. equi population visualized in Microreact. The dendrogram was reconstructed from pairwise cgMLST scores using the ape package [25]. The resulting tree was midpoint rooted using the phangorn package [26]. The scale bars relate to horizontal branch lengths and indicate the number of cgSNPs that are proposed to have occurred on the horizontal branches. Coloured circles indicate the country from which the isolates originated, as indicated in the key. (a) The phylogenetic relationships of the 106 isolates in the BAPS-1 subtree. Three sub-groups are numbered. (b) Pinnacle IN vaccine strains in sub-group 1 and clinical isolates from New Zealand and Montana (USA). (c) Sub-group 2 contains isolate Jpn0092, and isolates from outbreaks in the USA and Israel. (d) Sub-group 3 contains isolates from outbreaks in the USA and Japan. Isolate names and year of isolation are shown. N/A, not applicable.

Fig. 3.

BAPS-2 is the dominant European cluster, with evidence of transmission between horses in the UAE. Midpoint-rooted phylogenetic reconstruction of the S. equi population visualized in Microreact. The dendrogram was reconstructed from pairwise cgMLST scores using the ape package [25]. The resulting tree was midpoint rooted using the phangorn package [26]. The scale bars relate to horizontal branch lengths and indicate the number of cgSNPs that are proposed to have occurred on the horizontal branches. Coloured circles indicate the country from which the isolates originated, as indicated in the key. (a) The phylogenetic relationships of the 325 isolates in the BAPS-2 cluster. (b) Phylogenetic relationships of isolates in one sub-group, which were recovered from three outbreaks of strangles in the UAE between January and June 2014, and cases in Poland, the UK and the Netherlands during 2017, April 2014 and 2013, respectively. The identity and year of the outbreaks from which the isolates were recovered is indicated on the right. nd, Not determined.

Fig. 4.

BAPS-3 is an Oceania cluster, exchanged with horses in the UAE. Midpoint-rooted phylogenetic reconstruction of the S. equi population visualized in Microreact. The dendrogram was reconstructed from pairwise cgMLST scores using the ape package [25]. The resulting tree was midpoint rooted using the phangorn package [26]. The scale bar relates to horizontal branch lengths and indicates the number of cgSNPs that are proposed to have occurred on the horizontal branches. Coloured circles indicate the country from which the isolates originated, as indicated in the key. The khaki arrow highlights the two isolates recovered from the UAE. Isolate names and year of isolation are shown.

Fig. 5.

BAPS-4 illustrates the international transmission of S. equi between Argentina, the UAE and the UK. Midpoint-rooted phylogenetic reconstruction of the S. equi population visualized in Microreact. The dendrogram was reconstructed from pairwise cgMLST scores using the ape package [25]. The resulting tree was midpoint rooted using the phangorn package [26]. The scale bar relates to horizontal branch lengths and indicates the number of cgSNPs that are proposed to have occurred on the horizontal branches. Coloured circles indicate the country from which the isolates originated, as indicated in the key. Isolate names and year of isolation are shown. nd, Not determined.

Fig. 6.

BAPS-5 is a European cluster that illustrates distant and recent introductions of S. equi . Midpoint-rooted phylogenetic reconstruction of the S. equi population visualized in Microreact. The dendrogram was reconstructed from pairwise cgMLST scores using the ape package [25]. The resulting tree was midpoint rooted using the phangorn package [26]. The scale bars relate to horizontal branch lengths and indicate the number of cgSNPs that are proposed to have occurred on the horizontal branches. Coloured circles indicate the country from which the isolates originated, as indicated in the key. (a) The phylogenetic relationships of the 126 isolates in the BAPS-5 subtree. (b) The Equilis StrepE subtree. (c) An example of a diverse outbreak strain from Germany and a closely related outbreak strain from the Netherlands. Isolate names and year of isolation are shown.

Fig. 7.

BAPS-6 contains geographically restricted sub-groups in the USA, UK, Saudi Arabia and UAE. Midpoint-rooted phylogenetic reconstruction of the S. equi population visualized in Microreact. The dendrogram was reconstructed from pairwise cgMLST scores using the ape package [25]. The resulting tree was midpoint rooted using the phangorn package [26]. The scale bar relates to horizontal branch lengths and indicates the number of cgSNPs that are proposed to have occurred on the branches. Coloured circles indicate the country from which the isolates originated, as indicated in the key. Isolate name and year of isolation are shown.