Not long ago, a colleague shared a tragic story about a man with a failing heart. The good news? He received a transplant and did well. But soon after, things went terribly wrong.
After returning home from the hospital, he suffered encephalitis and descended into a coma. Months later, despite full supportive care, he died.
His nemesis was West Nile virus (WNV), which is now our country’s leading mosquito-borne threat. In up to 1% of infected people (primarily those who are older, chronically ill, or immunosuppressed), it can either kill or cause neurologic damage ranging from acute encephalitis to long-term cognitive loss, paralysis, even Parkinsonian tremors. Ironically, WNV’s woes in nearly everyone else are so mild or non-specific that most are never diagnosed.
Now for some curious history. Only 24 years have passed since WNV first felled crows and other birds in New York City, at the same time entering humans via bites of Culex mosquitoes that had previously fed on infected avians. Four years later, the virus arrived in California. Its initial trans-continental spread made headlines, but that hasn’t always been true of its recent squalls.
So, here’s my question for today. Both as medical professionals and everyday citizens, have we become too complacent about WNV?
I fear the answer is yes — especially in mounting defenses and alerting high-risk people as it continues to harm.
Predicting WNV Outbreaks
Apart from its erratic effects on humans, forecasting WNV-outbreaks remains a challenge. As Scott Weaver, PhD, a leading medical entomologist and virologist at the University of Texas Medical Branch in Galveston recently told me: the virus is “very widespread, still zoonotic…[and although] it’s transmitted more efficiently by Culex mosquitoes when it’s hot, it does well both in drought and rainy conditions.”
Weaver was keeping things simple. If Weaver or other experts were creating a model, they would likely weigh further factors including: different reservoir birds and their immunity to WNV; local Culex vectors and their preferred hosts, such as birds versus equids (also affected) versus people; fluctuations in weather and climate change; and other variables like standing water and wind.
This raises a timely question: Can artificial intelligence (AI) help predict outbreaks? That’s the belief of Swiss and German researchers who recently used a high-performance AI framework to “disentangle the contribution of eco-climatic drivers of WNV-outbreaks across Europe,” which, from 2017 to 2018, saw a 7-fold rise in cases.
But even AI might not anticipate unique drivers like California’s 2007 housing crisis. According to an analysis published in Emerging Infectious Diseases, delinquent mortgage payments leading to abandoned homes and swimming pools facilitated the breeding of highly-competent Culex vectors which, in turn, fueled that year’s 276% uptick in cases in the Bakersfield, Kern County area.
In the U.S.’s largest-ever WNV outbreak to date — a 2021-2022 event in Arizona that resulted in close to 1,700 cases (two-thirds neuroinvasive) and 121 WNV-related deaths — a wetter-than-average “monsoonal season” likely played an out-sized role along with non-immune birds.
Some final, big-picture facts: Human infections in the U.S. mainly occur between July and October; and although major outbreaks have hit cities like Los Angeles, Chicago, and Dallas-Fort Worth, the highest rates of disease are actually seen in the Dakotas, Wyoming, and Colorado.
How To Slay a Mosquito
Let’s face it. Few of us fully adhere to personal anti-mosquito measures, such as faithfully applying repellent, wearing protective clothing, or remaining indoors during high-risk times. Nor do public health authorities typically add community-based measures such as truck-mounted or aerial spraying of insecticide until after a significant outbreak of any mosquito-borne virus has already struck.
In an essay in the New England Journal of Medicine specifically focused on West Nile virus, CDC experts recently acknowledged two under-utilized strategies: early-season adult mosquito control and preemptive larvicides (insecticides that kill the aquatic mosquito larvae).
Thank God for “Don’s Drop Dead,” the pest control company that regularly services my own backyard. Last month, they placed two 1-gallon traps containing a fungus-based pesticide plus pyriproxyfen, an agent that persists for months, sterilizes adult female mosquitoes, gets transferred by those same females to other aquatic habitats, and then — even at very low doses — kills mosquito larvae.
What About a WNV Vaccine?
The last year has brought exciting news about prospective vaccines for chikungunya and dengue, two hugely important, global Aedes mosquito-borne viruses that occasionally breach our shores in places like Texas and Florida. (Although Takeda, the latest dengue vaccine manufacturer, recently withdrew its application for FDA approval, in the future the company will likely re-submit its product for possible use by U.S. travelers and residents of Puerto Rico; in the meantime, Takeda’s TAK-003 vaccine has already been licensed in several other endemic and non-endemic countries.)
On the other hand, neither dengue nor chikungunya have WNV’s unique potential to kill or maim older or immunosuppressed people and others with diabetes, chronic kidney disease, or a history of cancer right here at home. Even people taking certain monoclonal antibodies for anything from inflammatory bowel disease to rheumatoid arthritis to psoriasis have reason to fear mosquitoes. In fact, just last month, a paper underscored the much-enhanced risk of deadly, neuroinvasive disease in WNV-infected patients receiving rituximab (Rituxan), a B-cell depleting monoclonal antibody.
A WNV vaccine would be a terrific tool to protect these vulnerable individuals and others. Veterinary vaccines are already licensed, and several candidate vaccines for humans have shown real promise in Phase I and II trials. But major obstacles still exist, not the least of which is WNV’s unpredictable outbreaks, which could easily foil efforts to collect useful data from far larger (and more expensive) Phase III trials.
Bottom line: although experts have stated that current strategies will not reduce WNV’s ongoing burden of disease, when it comes to adding a vaccine to our armamentarium, the situation may have to get a whole lot worse before it gets better.
Pressing Priorities
What should we do now that WNV season is once again nigh? We must better educate high-risk individuals; encourage anti-mosquito measures; make sure that state and local vector-borne agencies capture the best possible data about emerging hot-spots; and keep a weather eye for dead birds, especially crows, blue jays, and ravens that often herald local WNV outbreaks.
In addition, did you know that the U.S. desperately needs more medical entomologists? Decades ago, “almost every big land grant university in the country had a graduate program in medical entomology,” Weaver told me. “Now, at least half of them have disappeared, maybe more.”
One thing is clear. Mosquitoes bearing pathogens aren’t disappearing anytime soon.
Claire Panosian Dunavan, MD, is a professor of medicine and infectious diseases at the David Geffen School of Medicine at UCLA and a past-president of the American Society of Tropical Medicine and Hygiene. You can read more of her writing in the “Of Parasites and Plagues” column.
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