Scientists eradicated smallpox, caused by the variola virus, in the 1980s using a similar virus that caused pox in horses, cows, and rodents. Unfortunately, that similar virus—vaccinia—could very well have started its own series of pox outbreaks just a few years later in India, Pakistan, and Brazil. Since the first cases appeared in dairy cattle (and the humans that milked them) in 1999 in Brazil, the numbers have been increasing steadily. To date, the country has now had to manage three vaccinia pox outbreaks in equids.

A breeding center in southern Brazil reported the country’s first official pox outbreak in horses in 2008, and several farms in southeastern Brazil reported the second such outbreak three years later. Then a handful of donkeys and mules in the northeastern part of the country fell ill in 2014.

But mystery continues to surround these episodes—how the equids got the vaccinia virus (VACV), why humans don’t seem to get it from equids, and why some equids get it in a population and others don’t. Iara Borges, PhD, of the Federal University of Minas Gerais Institute of Biological Sciences, in Belo Horizonte, Brazil, and colleagues have committed themselves to finding answers.

“Studying the outbreaks of VACV in horses and, even better, studying and monitoring the circulation of VACV in equids, is important to help understand why outbreaks popped up in Brazil recently and, therefore, speculate over possible risks associated, such as an epidemic,” she said. “It’s been circulating in Brazil since at least the first reported outbreak in dairy cattle in 1999. So we want to know, why these outbreaks now? Are they related to the virulence of different strains? Are they related to the immune status of the affected population? Are they related to another simultaneous pathogenic infection? Can outbreaks be prevented, and if so, how?”

To try to address those questions, Borges and colleagues retroactively examined blood samples taken from more than 600 equids at three time periods—including a two-year period starting five years before the first official outbreak. The equids lived in seven different regions of the state of Minas Gerais.

The scientists found that slightly more than 20% of the tested equids were positive for antibodies against any “orthopox” virus, even though most animals were selected for testing randomly or for reasons other than pox research, Borges said. In fact, many of these animals apparently never showed clinical signs of infection, their owners reported.

What’s more, a significant number of animals from the early blood samplings had positive results—meaning VACV was probably circulating among Brazilian equids for years before an actual outbreak and without anyone being aware of it.

“Our research indicates that horses had been infected with an orthopoxvirus, and since VACV is the only orthopoxvirus ever detected in Brazil, we assume this immune response derived from horses’ prior contact with this specific virus,” she said.

Interestingly, Borges added, this wasn’t surprising news to her research team. They’d long suspected “silent” VACV infections in horses in large part because of the role horses played in eradicating smallpox.

“The relationship among equids and VACV had been hypothesized to be older than the first outbreak reported, not only due to the similarities between VACV and horsepox virus,” she said, “but also because horses had been used to multiply VACV during the World Health Organization’s Smallpox Eradication Campaign in different countries around the world.”

In other words, during the smallpox eradication effort, scientists had used horses to produce the VACV-based vaccine they used to immunize humans and destroy smallpox.

Vaccinia could appear in horses in other countries, even if the disease never travels out of Brazil, Borges said. “The smallpox eradication campaign took it to wherever it had not yet been,” she said.

In India, Pakistan, and Brazil, these vaccinal strains might have “gone feral”—meaning they reproduced within their hosts and then spread on their own to new hosts. But it’s also possible that the virus was already in natural circulation before the vaccine was developed, Borges said.

It’s difficult to understand how VACV spreads, she added. Like most orthopoxviruses, including the cowpox virus, VACV can travel to various species, affecting each differently. It’s possible that it infects rodents who might carry it silently to horses, cattle, buffalo, monkeys, and humans. Scientists still don’t know whether horses pass it to each other or to humans, Borges said.

While not a fatal disease, vaccinia pox in horses can be uncomfortable and unsightly. Affected animals develop contagious exanthemas (pox lesions) on their muzzles and mouths, which go through several stages: macule, papule, vesicle, pustule, ulcer, and scab. The lesions heal on their own after about 10 days if treated properly, Borges said. “That means the animals must not be submitted to work of any kind, and the lesions must be kept clean, ideally with iodine (2-3% solution) for topical use,” she said.

“Humans must manipulate these lesions only with disposable gloves, and lesions must never be debrided,” Borges continued. “Infected animals must be isolated from healthy ones (all animals, not just equids), and feeding/water recipients or horse equipment must not be shared with others.”

In the meantime, officials and caretakers can reduce the risk of spread through good biosecurity across borders, said Borges. “A clinically infected horse with exanthemas must not receive permission to travel, even if the professional responsible for the exam does not recognize the lesion,” she said. “Unfortunately, however, there remains the possibility that the virus could be shed by subclinical horses.”

The study, “Serological Evidence of Orthopoxvirus Circulation Among Equids, Southeast Brazil,” was published in Frontiers in Microbiology.