On May 31,2017, 58-year-old Tamela Wilson checked into Barnes-Jewish Hospital, in St. Louis, with a fever, fatigue, and a strange red rash. She’d been undergoing chemotherapy to treat a relapsing lymphoma, but this exhaustion wasn’t just the cancer or the drugs. She told the doctors she worked at nearby Meramec State Park, tending to its miles of trails through forested river bluffs. And that while there, a week before her symptoms started, she found twoticksburrowed into her body.
Wilson’s doctors tested her blood for Missouri’scommon tick diseases. On day three, when the results came back negative, they sent a vial to Fort Collins, Colorado, to the Centers of Disease Control and Prevention’s Division of Vector-Borne Diseases, for a more extensive analysis. On day 10, they got their answer: Bourbon virus. Thirteen days later she was dead.
At the time, Wilson was one of only a handful of people in the world to ever be diagnosed with a Bourbon virus infection, and the second to succumb to the mysterious microbe since it was discovered in 2014. Two years later, the strain of virus that once coursed through Wilson’s veins lives on in freezers and petri dishes a few buildings over from where she died, as researchers race to find possible treatments for the next time.
Scientists know almost nothing about how Bourbon virus behaves or how it got here or where it will show up next. But they have learned enough to know they haven’t seen the last of it.
What they fear most is that the virus could be silently spreading through human populations, only getting noticed when it causes severe symptoms in an unlucky few. That’s what’s started to happen with anothernew tick-borne virusin Missouri. If Bourbon virus were to establish itself there in humans too, the chances go up that more cases, like Wilson’s, will turn deadly. And until someone conducts the necessary studies, there’s no telling how far the virus has spread or how many people might potentially be in danger.
Under a microscope, Bourbon virus is a shape-shifter, sometimes long and filamentous, sometimes a sphere studded with spiky proteins, encapsulating a string of segmented genetic code. It’s the only human pathogen of the genusThogotovirusto make it to the New World. Its nearest evolutionary relatives are viruses found in the bodies of sheep-sucking ticks in Kyrgyzstan and camel-chewing ticks in India, both of which attack neurons and cause brain inflammation when transmitted to humans. Bourbon virus appears to have developed a taste for other types of human cells during its travels; in the few documented cases that have appeared in the US, patients have experienced massive declines in their white blood cell populations.
Like its closest cousins, Bourbon virus seems to spend at least some of its time in ticks. The patient the virus was first isolated from—a 68-year-old man named John Seested in Bourbon County, Kansas—had a history of tick bites. The summer after its discovery there, CDC researchers found the virus in the bodies of several ticks collected elsewhere in Bourbon County. The species they found carrying the virus was the Lone Star tick, whose bite is more notorious for making peopleallergic to red meat. It’s also been shown to replicate inside tick cell lines in the lab.
But the CDC has yet to formally declare Bourbon virus a tick-borne disease, which would require states to report any cases to the federal agency. To definitively link Bourbon virus with its suspected vector, the agency needs more data—specifically on how well Lone Star ticks acquire, maintain and transmit the pathogen in a lab. Aaron Brault, a microbiologist with CDC’s Division of Vector-Borne Diseases, says those studies are currently in progress. He says it’s now a “strong probability rather than simply a possibility” that the virus is transmitted to humans through ticks.
Jocco Boon, a virologist at Washington University whose lab is located on the same block as Barnes-Jewish, the university teaching hospital, had lots of other questions. “But the first thing I wanted to know was ‘could this virus be treated?’” he says. Wilson’s infectious disease doctors reached out to their colleague because Boon studies a distantly related cousin to Bourbon virus—influenza. And he had a hunch that an experimental drug that curbs influenza’s ability to replicate might work on this enigmatic emerging virus too.
Within a month of her death, Boon’s team had cultured Wilson’s strain and used it to infect human cells in petri dishes. They watched as the virus torpedoed through the stained cells, hollowing out clear craters on the plate’s purple surface. But when they added a drug called favipiravir to infected cells, they survived. And the amount of Bourbon virus circulating in the culture plummeted nearly a million-fold.
Favipiravir is shaped like a nucleotide, thebackbone building blockof DNA and RNA. Viruses steal a cell’s nucleotides to make more copies of itself, using a special enzyme as their engine of self-replication. When that enzyme grabs favipiravir instead of a nucleotide, the virus’s multiplication machinery gets gummed up and grinds to a halt. The drug is available as a flu treatment in Japan, where it was developed, but has not yet been approved in the US. Boon’s team found that the drug also had a protective effect in mice with compromised immune systems, leading to a 100 percent survival rate. Compromised mice that didn’t get the drug all died within a week of infection (normal mice are not susceptible to Bourbon virus). It’s not proof that the drug works in humans, but the data,published last month, is the first to suggest Bourbon virus has a chemical vulnerability that doctors could try to exploit in the future.
Boon had planned to devote his life’s work to influenza. But since Bourbon virus struck in his backyard, his lab is now central to unraveling the pathogen’s many riddles. In addition to Wilson’s strain he’s since acquired other clinical samples, including from patient zero. Seested and Wilson are the only known fatalities to date, and though they came in with similar symptoms, they deteriorated in strikingly distinct ways at the end. Understanding how the virus varies genetically may help explain who it infects, and even track its origins beyond its abrupt arrival in Seested’s body in 2014.
To get at his biggest questions, Boon is now trying to set up studies to test the blood of lots of people in Missouri and Kansas forantibodiesto Bourbon virus and assess how many of them have ever been exposed to it. That will reveal whether the disease is rare and typically deadly, or if it’s actually more common and mostly innocuous with lethal outcomes being the outliers. According to the CDC, there have been no reports of the virus anywhere outside the US. “You don’t have to go to the Congo to find emerging viruses,” says Boon.
Since 2004, seven diseases believed to pass from ticks to humans surfaced for the first time on US soil, including Bourbon virus. According to a2018 CDC report, the pace of emergence of new, obscure, and dangerous vector-borne pathogensappears to be increasing. Some scientists counter that this alarming trend may just reflect advances inDNA-based diagnosticsthat can pick out previously unknown viruses and bacteria that have actually been sickening people (and confounding doctors) for a while. But asclimate change, suburban sprawl, and increased international travel are putting more ticks and the pathogens they carryin the paths of humans, what’s becoming more urgently apparent is how the US’s tick monitoring systems are not keeping pace.
“It’s really a patchwork in terms of the effort that different areas are putting into surveillance,” says Becky Eisen, a tick biologist with CDC’s Division of Vector-Borne diseases. The federal public health agency maintains national maps of the ranges of different tick species, but they’re extrapolated from scattered data collected in large part by academic researchers. Only a few states, mostly in the Northeast, have dedicated tick surveillance and control programs. That leaves large parts of the country in adata blackout.
To help address that problem the CDC is funding an effort to identify the most urgent gaps in surveillance. It has also begun publishingguidance documentsfor public health departments on how to collect ticks and test them for diseases, to encourage more consistent data collection across different states and counties.
In an ideal world, says Eisen, every county in the US would send a few well-protected people out into fields and forests every spring and summer, setting traps or dragging a white flannel sheet between them to collect all the ticks making their homes in the grasses and underbrush. Their precise numbers, locations, and species would be recorded so that later on when they get ground up and tested, that DNA would paint a national picture of risk for exposure to every tick-borne pathogen in America. But she recognizes that would be incredibly labor-intensive, and with only so many public funding dollars to go around each year, there are always competing priorities.“But from a research perspective, that’s the kind of repeatable, consistent data we’d really want,” says Eisen. “That would be the dream.”
For now though, she’ll take what she can get. The CDC recently changed the way it funds state health departments, allowing local agencies more flexibility to put the money toward tick-tracking projects if they so choose. It still might not be enough. In Missouri, for example, the state has started to spend more of its allotted CDC funds on combating tick-borne disease—$76,471 in 2018 compared to $22,624 in 2017. But according to a Missouri health department spokesperson, the state focuses its efforts not on surveillance but on education and awareness campaigns. Sending people out into fields is expensive, and not always satisfying. In the months after Wilson’s death, as Boon’s lab was working to grow more copies of the virus, Missouri’s department of health sent teams of researchers into Meramec State Park to look for copies in the wild. After collecting and testing more than 7,000 ticks, no trace of Bourbon virus was found.
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