Jennifer Tank didn’t think much of the mosquito bite. The mosquitoes had been bad near her home in Avondale in the summer of 2016, but she was used to them.
Then she started to feel like she had the flu. Next came the body aches, stomach issues and a blotchy red rash that stretched over her arms, chest and back.
A few days later, a doctor decided to run a test for West Nile virus. She tested positive.
Tank developed meningitis, then encephalitis. She lived in a fog. She forgot how to use words. Barely able to walk, she slept as much as 20 hours a day.
She had to call an ambulance three times that summer. But there is no cure for West Nile.
“There was nothing (the doctors) could ever do for me,” she said. “‘Go home and wait to die’ is what it always felt like.”
West Nile virus has reached record numbers in Arizona this year — 550 confirmed and probable cases so far, after a heavy monsoon that allowed the mosquitoes that spread the disease to proliferate. Much like COVID-19, some people can become infected with West Nile but feel no symptoms, while others experience the disease as a life-altering condition resulting in serious long-term medical problems or disabilities. This year, over half of recorded cases have been symptomatic.
But unlike COVID-19, there is no human vaccine for West Nile virus. That’s despite the fact that West Nile has been present in the U.S. since 1999 and in Arizona for 18 years, while COVID-19 has only been around for two. With development on a West Nile vaccine for humans making slow progress and no ongoing clinical trials for West Nile-specific therapies, environmental agencies and researchers have turned to virus surveillance and vector control to keep the disease at bay.
That means setting mosquito traps, treating high-risk areas with chemicals, and using genetic tracking techniques to better understand the life cycle of the virus. But even though researchers have a variety of technologies in their arsenal, controlling West Nile virus is not easy. That worries survivors like Tank, who follow the numbers with concern.
Already this year, as of mid-October, 27 people have died in Arizona, more fatalities than any other year on record.
“Why is (over 20 fatalities) not enough people to make a vaccine or get a treatment?” Tank asked. “It’s so frustrating.”
West Nile virus in Maricopa County:What you need to know about the illness
Monitoring West Nile virus
When Antonio Laguna notices standing water, whether it’s in a plastic children’s toy or on a park lawn, he checks for mosquito larvae. It’s become a habit.
He’s gotten good at spotting them. Laguna has worked for five years as a vector specialist for the Maricopa County Environmental Services Department.
Every week, he sets mosquito traps by filling containers with dry ice, which emits carbon dioxide that attracts the insects. The dry ice “acts kind of like a human,” Laguna said. “(Mosquitoes) smell (the dry ice), and they get tricked into the net.”
Once Laguna collects the specimens, he takes them to the Maricopa County Vector Control Division lab, where technicians can sort them by species. Lab techs can then further sort Culex mosquitoes, which carry West Nile, into harmless males and human-biting females.
Laguna and his colleagues hope their vigilance will pay off. If there are any West Nile-positive mosquitoes, 30 or more female Culex mosquitoes, or over 300 mosquitoes of any species in a trap, vector control sprays the area to get rid of them. They also encourage residents to eliminate sources of standing water, with the goal of stopping breeding sites from creating new generations of biting mosquitoes.
The 831 traps the county sets every week are “the most I’ve seen anywhere,” said managing supervisor Jim Will, who has worked in vector control for 32 years. But despite their best efforts, he explained, the work done by the Environmental Services Department does not necessarily translate into fewer West Nile cases in humans.
Because their budget is tight, Will said, vector control has to work with the resources they have. They break the county into three monitoring districts, each of which has nine or ten inspectors and a supervisor. More funding would allow the agency to make districts smaller and hire additional staff. Right now, every specialist is in charge of an average of about 30 mosquito traps, and must move each trap somewhere within its designated one-square-mile area according to resident complaints and their knowledge of the region.
Proactively eliminating all West Nile-carrying mosquitoes might not be possible, but a larger staff would mean each investigator could spend more time in their designated location. It would also create more bandwidth to respond to the flood of resident complaints that accompany heavy monsoon storms.
Mosquitoes are only half the story. The virus was first discovered in the West Nile region of Uganda in 1937 and identified in crows in Egypt in 1953. Mosquitoes that bite infected birds spread the disease to uninfected birds, and some birds die, but others mount an immune response. Those surviving birds pass the virus on to other mosquitoes, which occasionally infect humans and other animals as an unfortunate byproduct. That’s where researchers like Crystal Hepp come in.
Hepp is the assistant director of the Pathogen and Microbiome Institute at Northern Arizona University. She explained that it is critical to understand which bird hosts harbor West Nile in order to better understand how, where and why the virus persists year after year.
Hepp and her team use genetic technology straight out of “Jurassic Park”: By sampling the blood from a mosquito’s last meal, they can determine what species of bird it feasted on, whether or not that bird had West Nile, and if it did, exactly what strain of the virus was present.
This week, Hepp and her team released a tracking website that, much like TGen’s variant tracker for COVID-19, helps her and her team monitor different strains of West Nile virus. In 2019, a joint study produced by Hepp and other researchers from NAU and TGen identified a specific strain of West Nile that had become endemic to Arizona. Now, Hepp is continuing to watch the evolution of that strain to find out whether the viral variant circulating in Maricopa County has become more severe.
“I think that if we’re able to keep the (tracking) dashboard populated over time, it can give people a better understanding of risk in their location,” Hepp said. She also hopes that by developing a fuller understanding of the cycles of the virus, public health officials will be better equipped to intervene and slow down or stop its transmission.
But while Hepp has made significant progress, many of her questions remain unanswered. Do the strains of the virus found in Arizona manifest more neuroinvasive symptoms in humans than other strains do? How does the virus persist through the winter? Which bird hosts should be monitored more closely?
Hepp and her team are starting to develop some ideas. But like many other infectious disease researchers, they need more time to be sure.
From cases to clinical trials
Mark Slifka has been working on a West Nile virus vaccine for over a decade. Since he started out, he’s seen a shift in the way the public understands vaccine development —especially recently, after the COVID-19 pandemic.
“COVID has really changed the landscape in terms of how quickly things can be done,” said Slifka, a vaccine researcher at Oregon Health & Science University. “But I think people may have forgotten that prior to COVID, it usually took between eight to 15 years to get a vaccine from an idea to something actually commercially available.”
The relatively low number of West Nile cases has been a roadblock for development of a vaccine. In Phase III clinical trials, a significant number of individuals has to be infected and enrolled in order for a vaccine or treatment to demonstrate efficacy. Only a proven effective vaccine will be approved for use in humans, explained Deepta Bhattacharya, an associate professor of immunobiology at the University of Arizona.
“That was one of the reasons why the SARS-CoV-2 vaccines were able to be deployed so quickly: at the time Pfizer and Moderna were testing the vaccine, there was a ton of community spread,” Bhattacharya said.
Slifka said that COVID-19 vaccine developers also had the unique advantage of receiving funding, regulatory coordination and manufacturing support from the federal government and drug companies.
“It’s really hard for a small group or a small company to manufacture commercial-scale vaccines,” Slifka said. He added that big pharmaceutical companies, when deciding which diseases merit the development of vaccines, consider whether they will “be able to produce enough vaccine and sell to enough people to actually have a profit for (their) investors.”
One pharmaceutical company, Sanofi Pasteur, began development for a West Nile vaccine that completed Phase II clinical trials in 2009. When asked why they halted development, a representative from the company said the decision was “consistent with our strategy and priorities.”
A total of 9 clinical trials for human West Nile virus vaccines are listed on clinicaltrials.gov, but none has progressed past Phase II. Slifka hopes that will change one day, adding to the tools that are available to combat West Nile and providing more options for elderly, immunocompromised or otherwise at-risk populations.
“You want to hit (West Nile) from multiple angles,” Slifka said. Vector control helps for now, he added, but “if you had a vaccine in your arsenal, you’d definitely want to be using it.”
Horses and humans
Dr. Debbie Chapman has been a veterinarian for 25 years. When West Nile first came to the United States, she had a mobile large animal practice where she treated some of the first horses in Arizona to contract the virus.
Since then, she hadn’t seen too many West Nile cases. Until this year.
So far, three horses have arrived at her clinic with neurological symptoms. One was already unable to walk. Another began stumbling after a few days, despite Chapman’s best efforts to ease its symptoms. The third stayed in a dark stall for a week, unsteady and weak.
Only the third horse survived. Chapman had to put down the other two. She was glad she had even remembered West Nile as a possibility for diagnosis.
“When something’s been gone for 20 years, it’s not really at the forefront of your mind that that could be the problem,” said Chapman, who now works at Desert Cross Veterinary Hospital in Thatcher.
Chapman noted that after West Nile virus first arrived in the U.S., farmers were vigilant about vaccinating their horses. Though there is no vaccine for humans, there has been a vaccine for horses almost as long as West Nile has been in the country, and horse owners quickly incorporated it into routine immunizations for their animals.
Over the past two decades, though, Chapman said she has seen the price of the equine vaccine double. That means more horse owners willing to take a gamble on what they see as a rare disease.
“In a rural ranching community where money is tight for everybody and the cost of the vaccine keeps going up, you think, ‘I don’t want to spend 45 bucks and I have 10 horses, that’s 450 bucks,” Chapman said. “(Ranchers think), ‘what are the chances of (my horses) getting this?’”
But even if some are deterred by the price, horses still represent a significant market for the West Nile vaccine. First released in 2003 by animal health company Zoetis, over two million doses of the equine vaccine are now administered every year.
A spokesperson for Zoetis said their vaccine accounts for about half of those doses, but did not provide details related to the price increase.
With such a large market, researchers like Slifka see potential for animal vaccines to provide the proof of principle that drug companies need to initiate more research on a human vaccine.
“There’s actually a lot we can learn from veterinary medicine. Because there is a vaccine that works for horses, that tells you that there should be a way to make a vaccine that works for humans,” Slifka said.
While many diseases do not affect animals in the same way they affect humans, Slifka says the West Nile virus parallels between horses and humans represent an opportunity for more dialogue among vaccine experts.
“People are realizing that there’s a lot of good science being performed, but they’re in their own silos,” Slifka said. “By building on the cross talk between veterinary science and clinical science, you can get the best of both worlds.”
Community amid challenges
After five years, Tank continues to feel the effects of her diagnosis. She has an enlarged heart, kidney issues and persistent fatigue. She can’t go into the sun without developing a searing skin reaction.
For symptomatic patients, complications like Tank’s aren’t uncommon. This year, 345 of 550 West Nile patients experienced encephalitis or meningitis — swelling of the brain and spinal tissue — as a result of the virus, both conditions that often inflict lasting damage to the brain, kidneys and other vital organs. Tank considers herself lucky, despite the severity of her symptoms. She knows other West Nile survivors who are quadriplegic, paraplegic or have a permanent tracheostomy tube.
And like some other patients with severe West Nile cases, every year, around her “anniversary” of being diagnosed, she experiences what she calls a “flare.” Tank describes it as a flashback of her initial symptoms.
“It’s like I’m getting West Nile virus again every year,” Tank said.
She said she has taken comfort in a nationwide West Nile virus support group for survivors on Facebook, which has about 1,900 members. “There’s a lot of long timers in the group that do give lots of really good advice (even as they) still suffer,” said Tank, who said she has noticed a recent influx of new members from Arizona.
Members share personal experiences and offer suggestions on potential treatments. “This group has become lots and lots of hard work, but I want people to have facts,” said Jane McGahen Myers, an administrator for the group.
While they search for specialists and wait for future West Nile treatments, Tank said she and other survivors rely on one another for encouragement and support that they have not found in the medical or research communities.
“(The online forum is) a blessing,” Tank said. “All of a sudden, when I found that group, I wasn’t alone anymore.”
Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.