Deadly virus transmitted by ticks cured with an experimental drug against influenza, in mice

Only a few cases of newly discovered Bourbon virus have been reported, and two of them have resulted in death, in part because no specific treatment is available for tick-borne disease. Researchers at the University of Washington School of Medicine in St. Louis have identified an experimental antiviral drug that cures mice infected with the potentially lethal virus. The drug, favipiravir, is approved in Japan but not in the United States for the treatment of influenza, a related virus.

"Without the flu, 100% of the infected mice died and, with the treatment, 100% survived," said Jacco Boon, Ph.D., assistant professor of medicine and lead author of the journal. "Until now, the doctors had no way of treating the Bourbon virus, we found something that works, at least in the mouse, and this suggests that the antiviral flu is a good place to start looking for a treatment for Bourbon. "

The results are published June 13 in the journal PLOS Pathogens.

The Bourbon virus was first identified in 2014 in a previously healthy middle-aged man in Kansas. The man arrived at the hospital with flu-like symptoms and a history of tick bites. Thinking that he was suffering from ehrlichiosis, a tick-borne bacterial infection that causes similar symptoms and often affects Midwesterners, doctors have prescribed him antibiotics. But the man continued to decline and testing for Ehrlichiosis and all other infections that doctors could think of was negative. After his death, 11 days later, a sample of his blood was sent to experts from Centers for Disease Control and Prevention (CDC), specializing in mysterious infections. The CDC researchers identified a new virus and named it Bourbon after the county where the patient had lived.

A second case appeared in the Saint-Louis region in 2017, in a woman who arrived at the Barnes-Jewish hospital in Saint-Louis, complaining of fever, fatigue and body aches. Jennie Kwon, DO, an infectious disease specialist at the University of Washington, assistant professor of medicine, worked with the CDC to identify the Bourbon virus, which has similarities to the influenza virus, as the cause.

"We were able to tell the patient and her family that we had identified the cause of her illness, but the misfortune is that there was no antiviral treatment available," said Kwon, also an epidemiologist at the hospital. from Barnes-Jewish. an author on paper. "The team did its best to provide supportive care, but unfortunately, it did not survive."

The case of this woman has attracted the attention of Boon, a researcher of the influenza virus who works with Kwon and other infectious disease specialists. With the influenza virus being a distant cousin of the Bourbon virus, Boon and his colleagues have been investigating whether any of the drugs approved or under development for the flu could stem the Bourbon virus.

The researchers quickly narrowed the list of potential drugs to one, favipiravir, which inhibits a key protein that the virus needs to multiply. The other drugs available against the flu probably would not work because they target parts of the influenza virus that differ from the Bourbon virus.

As Bourbon virus infections are rare, Boon and his colleagues have not been able to study the drug potential in humans. Instead, they infected the virus with mice, using a mouse strain whose immune system was weakened, healthy mice able to fight the virus. All immunocompromised mice died six to eight days after their injection of the virus.

In a separate experiment, the researchers treated mice infected with the anti-influenza drug or placebo for eight days. When mice received the antiviral at the same time or less than a day after being infected with the virus, all survived without becoming visibly diseased. In contrast, none of the infected mice that received placebo survived. When the researchers administered the antiviral treatment three days after the infection, at a time when the mice already looked sick and had lost weight, all treated mice recovered.

Tick-borne infections are a growing problem in the Midwest, according to the CDC. Although very few people have been diagnosed with the Bourbon virus – a third case, a surviving patient, has been identified in Oklahoma – many others have been exposed to the virus but have not been sick enough to end up in hospital.

"We really have no way of saying how common the Bourbon virus infection is or whether it is deadly," said Boon, an assistant professor of molecular microbiology, pathology and disease. immunology. "The ticks have always been here and we now know that the Bourbon virus is present in this region.There have probably always been people infected with the Bourbon virus and we simply did not know what it was before. "

Since favipiravir is not approved by the FDA, it is not certain that US doctors can obtain it for their patients. The best protection against the Bourbon virus is to avoid tick bites by wearing long sleeves and long pants and an insect repellent, as well as by performing a regular check of ticks after an outdoor activity, said Researchers.