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May 31 2017, Tamela Wilson, age 58, was presented at the Barnes-Jewish Hospital, St. Louis, with fever, fatigue and a strange red rash. She was undergoing chemotherapy to treat recurrent lymphoma, but this was not just cancer or medication. She explained to doctors that she was working in the nearby Meramec National Park, traversing miles of trails crossing wooded cliffs. And during her stay there, a week before the onset of her symptoms, she found two ticks buried in her body.
Wilson's doctors analyzed his blood for diseases common to Missouri ticks. On the third day, when the results became negative, they sent a vial to Fort Collins, Colorado, to the Division of Vector-Controlled Diseases of Centers for Disease Control and Prevention, for further analysis. On the tenth day, they got their answer: Bourbon virus. Thirteen days later, she was dead.
At the time, Wilson was one of the few people in the world ever to have been diagnosed with the Bourbon virus infection and the second to succumb to the mysterious microbe since its discovery in 2014. Two years later, the strain of the Wilson virus, which once ran through Wilson's veins, still lives in freezers and Petri dishes a few buildings away from his death, while researchers run in search of possible treatments for next time .
Scientists know almost nothing about the behavior of the Bourbon virus, how it happened here or where it will manifest itself. But they learned enough to know they did not see the last end.
What they are most afraid of is that the virus can spread silently among human populations, only getting noticed if it causes serious symptoms in some. That's what started to happen with another new virus transmitted by ticks in Missouri. If the Bourbon virus is also needed in humans, there is a good chance that more cases, like Wilson's, become fatal. And as long as nobody has done the necessary studies, we will not know how much the virus has spread or how many people could be potentially at risk.
Under the microscope, the Bourbon virus is a metamorph, sometimes long and filamentous, sometimes a sphere strewn with spiked proteins, encapsulating a segmented genetic code chain. It is the only human pathogen of its kind Thogotovirus to make it to the new world. His closest relatives during the course of the evolution are the viruses found in the bodies of ticks to suck sheep in Kyrgyzstan and chewing ticks in India, both attacking neurons and causing inflammation of the brain when they are infected. they are transmitted to the man. The Bourbon virus seems to have developed a taste for other types of human cells during his travels; In the few documented cases that have emerged in the United States, patients have experienced a massive decline in their white blood cell populations.
Like its closest cousins, the Bourbon virus seems to spend at least part of its time in ticks. The patient whose virus was isolated for the first time – a 68-year-old man, John Seested, in Bourbon County, Kansas – had a history of tick bites. In the summer after its discovery, CDC researchers discovered the virus in the bodies of several ticks collected elsewhere in Bourbon County. The species found to be carrying the virus was the Lone Star tick, whose bite is best known for making people allergic to red meat. It has also been shown to replicate within laboratory tick cell lines.
But the CDC has not yet formally declared the Bourbon virus as a tick-borne disease, which would require states to report any cases to the federal agency. In order to definitively link the Bourbon virus to the vector it suspects, the agency needs more data, in particular on the quality of the acquisition, maintenance and control of the virus by Lone Star ticks in a laboratory. . Aaron Brault, a microbiologist in the CDC's Division of Vector-borne Diseases, says these studies are ongoing. He says that it is now "a high probability rather than simply a possibility" that the virus is transmitted to humans through ticks.
Jocco Boon, a virologist from the University of Washington, whose lab is located in the same block as Barnes-Jewish, the university hospital, asked many other questions. "But the first thing I wanted to know was" Can this virus be treated? "He said. Wilson's infectious disease physicians contacted their colleague because Boon is studying a cousin far removed from the flu virus, Bourbon. And he had the impression that an experimental drug that limits the ability of the flu to replicate could also act on this enigmatic emerging virus.
A month after his death, Boon's team had grown the Wilson strain and used it to infect human cells in Petri dishes. They observed the virus torpedo through the colored cells, digging transparent craters on the violet surface of the plate. But when they added a drug called favipiravir to the infected cells, they survived. And the amount of circulating Bourbon virus in the crop has dropped nearly a million times.
Favipiravir is in the form of a nucleotide, one of the building blocks of DNA and RNA. Viruses steal nucleotides from one cell to make other copies, using a special enzyme as a self-replicating engine. When this enzyme seizes favipiravir instead of a nucleotide, the multiplication machinery of the virus gums up and stops. The drug is available as a flu treatment in Japan, where it has been developed, but has not been approved in the United States yet. Boon's team discovered that the drug also had a protective effect in mice whose immune system was compromised, which allowed a 100% survival rate. Compromised mice that did not receive the drug all died within one week of infection (normal mice are not susceptible to Bourbon virus). This is not proof that the drug works in humans, but the data, released last month, are the first to suggest that the Bourbon virus has a chemical vulnerability that doctors might try to exploit in the future .
Boon had planned to devote his work to the flu. But since the Bourbon virus hit his yard, his lab is essential to solving the many riddles of the pathogen. In addition to the Wilson strain, he has since acquired other clinical specimens, including in the zero patient. Seested and Wilson are the only known fatalities to date, and although they had similar symptoms, they deteriorated sharply in the end. Understanding how the virus varies genetically can help explain who it infects and even trace its origin beyond its sudden arrival in Seested's body in 2014.
To answer his biggest questions, Boon is now trying to set up studies to test the blood of anti-Bourbon virus antibodies in the blood of many people in Missouri and Kansas, as well as to assess the number of people who have already been exposed to it. This will reveal if the disease is rare and usually fatal, or if it is actually more common and especially harmless, with life-threatening consequences being extreme cases. According to the CDC, the virus has never been reported anywhere other than in the United States. "You do not have to go to Congo to catch emerging viruses," says Boon.
Since 2004, seven diseases believed to be transmitted from humans to ticks have appeared on American soil for the first time, including the Bourbon virus. According to a report by the CDC of 2018, the emergence of new, obscure and dangerous vector-borne pathogens seems to be accelerating. Some scientists argue that this alarming trend may well reflect advances in DNA-based diagnostics to detect previously unknown viruses and bacteria that have actually made people sick (and confused doctors) for some time. But as climate change, suburban sprawl and increased international travel put more and more ticks and pathogens into the human path, it is becoming increasingly obvious that US tick surveillance systems are not following suit.
"It's really a patchwork of efforts in different areas of surveillance," says Becky Eisen, a tick biologist with the CDC's Vector-borne Diseases Division. The Federal Public Health Agency has national range maps of different tick species, but these are extrapolated from scattered data collected largely by university researchers. Only a few states, mainly in the north-east of the country, have established surveillance and tick control programs. This leaves large parts of the country in a data crash.
To help solve this problem, the CDC is funding an effort to identify the most urgent surveillance gaps. It has also started publishing guidance documents for public health services on how to collect ticks and test them for disease, to encourage data collection. more consistent in different states and counties.
In an ideal world, says Eisen, every county in the United States would send a few well-protected nationals into the fields and forests every spring and summer, setting traps or trailing a sheet of white flannel between them to collect all the ticks who settled there. grass and brush. Their precise numbers, locations and species would be recorded so that, when analyzed and tested, this DNA will paint a national picture of the risk of exposure to each tick-borne pathogen in America. But she recognizes that it would require a lot of work and that with public budgets every year, there are always competing priorities. "But from a research perspective, it's the kind of repetitive and consistent data that we want," says Eisen. "That would be the dream."
For now, she will take what she can get. The CDC has recently changed the way it funds state health services, giving local agencies greater flexibility to allocate funds to tick monitoring projects if they wish. This might not always be enough. In Missouri, for example, the state has begun to spend a larger portion of the CDC's allocation on tick-borne disease – $ 76,471 in 2018, up from $ 22,624 in 2017. However, according to a spokeswoman for the Missouri Department of Health, the state concentrates surveillance but on education and awareness campaigns. Sending people to the fields is expensive and not always satisfying. In the months following Wilson's death, while Boon's laboratory was working on making copies of the virus, the Missouri Department of Health sent teams of researchers to Meramec National Park to search for copies of the virus. the wild state. After collecting and testing more than 7,000 ticks, no trace of Bourbon virus was found.
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