Microbial forensics to the fore in unravelling disease outbreak among Icelandic horses

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Streptococcus zooepidemicus
Streptococcus zooepidemicus.

Iceland’s scientific investigation into a mysterious respiratory illness that affected its horses shows the power of genomics to unravel the cause of a significant biosecurity threat, an expert says.

Dr Mark Davies, a University of Melbourne specialist in bacterial genomics, praised the microbial forensic work undertaken to get to the bottom of the 2010 outbreak.

Iceland is free of all major horses diseases thanks to a ban on importing horses into the country that has applied since 1882.

The country’s 77,000 iconic Icelandic horses have enjoying a relatively disease-free environment for the last 1000 years, which makes them particularly susceptible to any new bacteria or viruses that cross the border.

Strict biosecurity regulations are in place to protect them. However, in 2010, a mysterious respiratory infection swept through the horse population, spreading across the country within weeks. It also affected dogs and cats, and some people fell ill.

Horse transportation was brought to a halt in a bid to contain the spread of the infectious agent.

Davies said Sigríður Björnsdóttir and his colleagues employed the power and resolution of “genomic epidemiology” – the combination of whole genomic sequencing and epidemiological approaches – to examine the source and spread of the outbreak.

Intriguingly, the outbreak was not viral in origin, but linked to a bacterial Streptococcus equi subsp. zooepidemicus infection.

A national sampling strategy coupled with population genomics revealed that the outbreak was most likely driven by a S. equi subsp. zooepidemicus sequence type 209 (ST209) infection that spread nationally from a single source.

The research showed the power of genomics applied on a national scale to unravel the cause of a significant biosecurity threat, Davies wrote in a commentary in mBio, the journal published by the American Society for Microbiology.

An Icelandic pony showing a nasal discharge.
An Icelandic pony showing a nasal discharge.

Davies noted that additional biosecurity measures were implemented by health authorities in Iceland as soon as the outbreak was detected.

“Yet by the time the alarm was raised, disease symptoms, recorded through electronic questionnaires sent to hundreds of equine breeding farms and professional training centers, were already widespread.”

Such rapid spread of a respiratory infection across a large area is typical of a viral agent. However, gene-based testing failed to identify a likely viral cause.

Björnsdóttir, from the MAST Icelandic Food and Veterinary Authority, and his fellow researchers analyzed nasal swabs from 100 horses at 31 different geographical sites, which led to the identification of the bacterium Streptococcus equi subsp. zooepidemicus as a common link.

It is usually a harmless organism found in the upper airways of horses, but is an opportunistic pathogen in a wide variety of mammals, including horses, and is capable of infecting people.

“This is not the first time S. zooepidemicus has been linked to a veterinary outbreak,” Davies notes.

“Equine outbreaks of S. equi subsp. zooepidemicus have previously been documented within New Caledonia and Scandinavia, and also within other hosts, such as dogs and pigs, but not at the national scale as documented by Björnsdóttir and colleagues in Iceland.”

Advancements in genome sequencing made it a valuable tool in determining outbreak sources and transmission pathways when quality sampling and epidemiological data were integrated in the study design, he said.

Davies praised the work of Björnsdóttir and his colleagues, saying it was a prime example of informed study design examining the genetic relationship of samples from cases, as well as historical, non-equine, and contemporary S. equi subsp. zooepidemicus isolates for context.

“The well-designed study, including the large sample number and several control sequences, coupled with high-resolution population genomics, allowed the team to draw their epidemiological conclusions.”

Key findings from this study identified that S. zooepidemicus sequence type 209 (ST209) was present in half of the disease isolates from most of the infected farms. Three other S. zooepidemicus sequence types were also variably present within some clinical samples, which the authors suggest may represent resident endemic strains.

A blue-eyed Icelandic horse. Photo: Anjali Kiggal CC BY-SA 4.0 via Wikimedia Commons
A blue-eyed Icelandic horse. Photo: Anjali Kiggal CC BY-SA 4.0 via Wikimedia Commons

It appears, Davies says, that both endemic (non-ST209) and outbreak pandemic (ST209) strains were circulating within the population at the same time, leading to challenges in drawing conclusions as to what causes led to the outbreak of disease.

One objective from a public health perspective is to identify the possible point source of the outbreak. Modeling by the researchers points to the ST209 progenitor being introduced around 2008 – a single introduction of the “new” genotype within a proposed immunologically naive population.

“Furthermore, through integrating population structure with GPS (Global Positioning System) coordinates of the isolates from infected animals, the authors were able to propose an outbreak transmission pathway.”

It led the authors to suggest an equine water treadmill at a single location as a potential point source, yet no isolates were identified from the environmental source in question in order to confirm the link.

Davies notes that the outbreak itself did not lead to a reported surge in human cases, “but the role of a human (or other) reservoir is possible with this outbreak.”

He says no matter how strict the biosecurity regulations around the importation of “foreign” animals, carriage by an intermediate host is near impossible to safeguard against.

This reiterates the need for high sanitary standards within animal practices, he says.

“Whether S. zooepidemicus ST209 is a globally disseminated clone and what genetic factors within the genome of ST209 isolates may account for the severity of disease remain unknown,” he writes.

“The authors of this research speculate that the infected equine population lacked protective immunity to the outbreak strain, and this remains an interesting hypothesis. What drives an opportunistic commensal [generally harmless] pathogen to cause disease is likely to be an intricate balance between host immune status, the genetics of the microorganism itself, and the environment.

“A community-wide shift in any of these elements could be enough to kick a commensal into gear. Elucidating these factors is key to understanding the drivers of outbreaks that in turn can be used in pathogen surveillance and diagnostics.

“Collectively,” he concludes, “the work by Björnsdóttir and colleagues highlights the power and utility of genomic epidemiology to investigate microbial forensics within a nationwide veterinary outbreak.

“Challenges remain in linking disease outbreaks with commensal-associated pathogens, yet this study highlights the value of a national reporting system and the benefit of an informed sampling strategy in identifying patterns of pathogen emergence and dissemination.

“Management of infectious diseases at both the national and international levels relies on coordination and knowledge sharing across animal and human health agencies under the auspices of a ‘one-health’ approach to address the intertwined relationship between veterinary, human, and zoonotic disease.”

Davies MR. 2017. Straight from the horse’s “mouth”: genomic epidemiology of an Icelandic equine epidemic. mBio 8:e01613-17. https://doi.org/10.1128/mBio.01613-17.

The commentary, published under a Creative Commons License, can he read here

Horsetalk’s report on the findings of Björnsdóttir and his colleagues can be found here

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