Horses were probably a major reservoir for influenza A viruses before the 20th century, and transmission between horses and humans may have occurred frequently, according to scientists.
Influenza A viruses are behind seasonal epidemics in people. The ability of influenza A viruses to rapidly cross between species and circulate in a variety of birds and mammals creates a breeding ground for zoonotic strains with pandemic potential.
Since the beginning of the 20th century, spillover events have given rise to multiple, well‐documented pandemic strains of the virus.
Susanne Kessler and her fellow researchers, in a just-published review, looked at the evidence around influenza A viruses and their tendency to jump between species, known as zoonotic transmission.
The review team, writing in the journal Viruses, said infections of humans with influenza A viruses from animal reservoirs can result in severe disease in individuals and, in rare cases, lead to pandemics.
“This is exemplified by numerous cases of human infection with avian influenza viruses and the 2009 swine influenza pandemic,” they said.
“In fact, zoonotic transmissions are strongly facilitated by man-made reservoirs that were created through the intensification and industrialization of livestock farming.”
This can be seen in the repeated introduction of influenza A viruses from natural reservoirs of aquatic wild bird populations into swine and poultry, and the emergence of partially or fully‐adapted human pathogenic viruses.
“On the other side, human-adapted influenza A viruses have been (and still are) introduced into livestock by reverse zoonotic transmission.
“This link to man-made reservoirs was also observed before the 20th century, when horses seemed to have been an important reservoir for influenza A viruses but lost relevance when the populations declined due to increasing industrialization,” they said.
Horses are a reservoir for two mammalian‐adapted influenza A lineages, the historic H7N7 and contemporary H3N8 subtypes. H7N7 constitutes the equine-1 lineage and H3N8 is the equine-2 lineage.
In 1956, a strain of the H7N7 subtype was isolated from a horse in Prague following an epizootic outbreak in former Czechoslovakia. The virus spread through the US in the 1960s, causing only relatively mild disease.
In 1963, after a flu outbreak in racehorses in Florida that affected 60-70% of the animals, an H3N8 virus was identified and designated as the equine 2‐lineage.
However, molecular analysis revealed that the H7N7 lineage had already emerged in the middle of the 19th century, coinciding with the 1872-73 horse epizootic outbreak. Similarly, the H3N8 equine lineage was found to have emerged during the 1800s.
Scientists in a 2010 review suggested that horses were probably a major reservoir for influenza A virus before the 20th century and transmission between horses and humans may have occurred frequently.
One major event, thought to be a form of influenza due to the symptoms and disease progression, was the same as the aforementioned 1872-73 horse epizootic event, which spread through the US along the rail lines where horses were transported.
The outbreak caused an extraordinary number of horse deaths and illness, paralyzing the US, as travel and transport by horses had to be stopped.
“During this time, cases of influenza in humans were often linked to exposure to horses,” the review team noted.
A horse‐derived H3N8 virus is thought to have caused the 1889-1890 human pandemic. Studies in 1965 found antibodies that were reactive to the equine H3N8 subtype in elderly people, and more than 80% of the tested people born before 1891 had specific antibodies.
“Importantly, this was before the first documented introduction of an H3 virus into the human or swine population in 1968, fueling the assumption that an H3 virus circulated around 1890.”
The last widespread influenza epizootic in horses was in 1915/16. Notably, the world horse population peaked between 1910 and 1920 with 110 million horses, and declined to about 60 million today.
In the US, the horse population peaked at about 25 million horses in 1914 and then declined until 1964 (at around 1.5 million horses) and finally increased again to about 10 million horses today. In contrast, the European horse population has declined consistently.
“While the H7N7 strain probably became extinct in the 1970s, the H3N8 strain still evolves globally in horse populations. As yet, no infections of humans have been reported.
“However, several more recent studies have found antibodies against equine H3N8, mainly in people with exposure to horses. Nevertheless, the antibody titers were very low and a cross‐reactivity to human seasonal H3N2 viruses cannot be excluded.”
The review team noted that experimental infection of volunteers in the 1960s showed a general susceptibility to equine influenza A viruses, with symptom-free or mild disease progression in two-thirds of the study participants.
In addition, the H3N8 equine viruses have jumped from equine to canine populations on at least two occasions, in Britain in 2002 and in the US since 1999.
“While only limited dog-dog spread was reported from a few kennels in the United Kingdom, the US canine cases developed into regional epidemics with cases being detected until at least 2016.”
Today, the overlap between humans and horses is limited to leisure activities and sport. “Despite being an important reservoir in pre‐industrial times, in a globalized and highly modernized world the importance of equine species as an influenza A virus reservoir has therefore decreased because of a declining population.
“Other animals, such as swine, whose numbers have steadily increased, have gained in importance.”
The authors said although influenza A viruses circulate in a variety of different animal species, livestock animals are becoming especially important as a reservoir for zoonotic flu transmission.
“The increased demand for animal products has driven the intensification of livestock farming and led to the introduction, adaptation, spread, and often endemic entrenchment of influenza A virus in these farmed animals.
“Consequently, the reported number of zoonotic infections increased in parallel to the extension and intensification of livestock rearing.”
Nowadays, poultry and swine are reservoirs of particular concern.
In particular, swine have been shown to be a potent “mixing vessel” for influenza A viruses of different species origins, and strains that are introduced by humans.
“Thus, a zoonotic event that results in sustained human-human transmission, such as the one that caused the 2009 pandemic, is not unlikely.
“Overall,” they continued, “intensified livestock farming has created an important interface between humans and animals and made zoonotic events that bear the risk of emergence of a human‐transmissible virus more likely.”
To reduce zoonotic events, it is important to control the spread of flu viruses within these animal reservoirs, for example, with efficient vaccination strategies. It is also critical to monitor the different man-made animal reservoirs to evaluate the emergence of new flu strains with pandemic potential, they said.
The review team comprised Kessler, Martin Schwemmle, and Kevin Ciminski, all with the University of Freiburg in Germany; and Timm Harder, with the Friedrich-Loeffler-Institute, part of the Institute of Diagnostic Virology, also in Germany.
Kessler, S.; Harder, T.C.; Schwemmle, M.; Ciminski, K. Influenza A Viruses and Zoonotic Events—Are We Creating Our Own Reservoirs? Viruses 2021, 13, 2250. https://doi.org/10.3390/v13112250