“I worry about cases of West Nile virus increasing over time without having anything to combat them. We are spending an incredible amount to control mosquitoes, for the constant surveillance of infected mosquitoes, and the clinical costs associated with West Nile virus cases. This virus isn’t going to go away.”
- Kristy Murray, DVM, PhD, assistant dean, National School of Tropical Medicine, Baylor College of Medicine
“Names are not always what they seem.”
- Mark Twain
West Nile virus (WNV) is an arbovirus that threatens not only humans but other animals as well, including horses and many species of birds. And don’t let this virus’s name lull you into thinking Americans need not be concerned about WNV. To the contrary, it is the leading cause of mosquito-borne disease and mortality in the continental U.S. In this Germ Gems post, I explain what WNV is and why it should be on our radar screen.
History and geography of WNV infections. The term “arbovirus” refers to a large group of RNA viruses that are carried by vectors, such as mosquitoes, ticks, and other arthropods. Scientists recognize 500 arboviruses worldwide, 150 of which are known to cause human disease. WNV is one of the latter—a mosquito-borne arbovirus that causes human disease. (In previous Germ Gems posts, I’ve mentioned other diseases caused by mosquito-borne arboviruses, e.g., dengue virus, Chikungunya virus, Zika virus, and Powassan virus.)
As its name suggests, WNV was discovered in the West Nile region of Uganda, in 1937. Over the next several decades, outbreaks of WNV infections occurred in Africa, Israel, several European countries, and Russia. But until the late 1990s, WNV disease was considered a relatively minor problem for humans in the U.S.
In the summer of 1999, Tracey McNamara, chief pathologist at the Bronx Zoo, first identified WNV in NYC. She was struck by the number of dead birds on the zoo grounds, including crows and flamingoes. At about the same time, doctors reported several fatal cases of encephalitis in patients in the neighboring borough of Queens. McNamara is credited with making the mental connection between the bird and human infections caused by WNV.
Scientists don’t know exactly how WNV made its way to America. The most likely explanation is that it got here via an infected migratory bird, or a stowaway mosquito on a flight from another country. But regardless of how it arrived within our borders, within a couple of years it spread to all of the lower 48 states and became the most common mosquito-borne pathogen in the U.S. killing a large number of birds as well as humans and other animals.
From 1999, when the virus made its debut in the U.S., to the year 2022, nearly 57,000 cases—about half of them neuroinvasive—and almost 2,800 deaths resulting from WNV were reported to the Centers for Disease Control and Prevention (CDC). But because WNV often isn’t on the radar screen of clinicians, the CDC estimates that millions of cases have occurred in the U.S. And given the impact of our warming planet on the expanded breeding terrain and season of mosquitoes, it’s anticipated that the incidence of WNV infections is going to climb.
The number of human WNV infections varies from year to year. In 2012, one of the worst years for WNV infections, 286 people died, with the state of Texas hit the hardest. In 2021, the biggest WNV outbreak in U.S. history occurred in Arizona, with three counties reporting more than 50% of all reported WNV cases nationwide. (Nationwide there were 2,911 cases of WNV that year.)
The promiscuity of the WNV. Some arboviruses are quite picky in terms of the mosquitoes they infect, such as the strict affinity of dengue virus, Zika virus, and Chikungunya virus for Aedes aegypti and Aedes albopictus mosquitoes. WNV is not so finicky; it is harbored by at least 65 different mosquito species (including a number of Aedes species, as well as Anopholes mosquitoes, the insects that carry the parasite that causes malaria). Mosquitos belonging to the genus Culex, however, are the main carriers of WNV.
WNV’s promiscuity extends to a broad range of animal victims, particularly birds. The virus has been found in more than 250 different bird species. Some birds of the order Passeriformes, such as sparrows, are reservoirs for the virus. This means that when a sparrow is bitten by an infected mosquito, WNV doesn’t kill it. Instead, the virus grows steadily—and, for the sparrow, harmlessly—inside the bird. The virus can then be readily picked up and transmitted via mosquitoes to other creatures, including humans.
Birds belonging to the Corvidae family, such as crows, ravens, and blue jays are dead-end hosts which means that WNV doesn’t just grow inside them—it kills them. As a result, since 1999, some areas of the U.S. have witnessed a devastating loss of many common backyard birds, including the American robin, the house wren, the chickadee, and the tufted titmouse.
Humans and horses are also dead-end hosts for the virus along with at least 24 other mammal species. (Although dogs and cats can be experimentally infected by mosquitoes harboring WNV, to date there’s no evidence of natural infection of these mammals.) And while it’s hard to imagine how mosquitos can penetrate their thick hides, even reptiles such as Eastern garter snakes and alligators aren’t spared from the deadly WNV.
The nature of human infection by WNV. According to the CDC, about 20% of people who are infected with WNV develop a fever and flu-like illness, with fatigue and weakness sometimes persisting for months. Less than 1% of infected people develop neuroinvasive disease, usually encephalitis (infection/inflammation of the brain parenchyma) or meningitis (infection/inflammation of the covering of the brain). Occasionally, acute flaccid paralysis resembling poliomyelitis or tremors and muscle rigidity, as seen in Parkinson’s disease, occur.
Who’s at greatest risk? People over the age of 70 have the greatest risk of a WNV-related neurological disease, probably because the body’s immune defenses wane with age (a process called immunosenescence). This idea is supported by the increased risk of WNV neurological disease for people who have a compromised immune system, such as organ transplant recipients.
Originally, the estimated fatality rate of 4% was attributed mainly to those with encephalitis who were over 70 years-of-age. But recent studies revealed that the fatality rate may be much higher because WNV infection leaves people who initially recovered more vulnerable to other infectious diseases and health problems. For example, researchers at Baylor University recently reported that nearly half of their patients who recovered from WNV eventually developed worsening neurological problems during the next decade.
Treatment and prevention. As with all the mosquito-borne viral infections in humans, there is no specific antiviral therapy for WNV infection. And a vaccine to prevent WNV in humans doesn’t yet exist. (A vaccine using killed WNV is available for horses, and some zoos give this vaccine to their birds. But, the effectiveness of this vaccine in these animal groups is unknown.)
Right now all that anyone can do to ward off the WNV is to use measures to control mosquito breeding and to take precautions to prevent mosquito bites. While these measures may be insufficient, that’s all we have. Therefore, if you’re in the over 70 years-of-age high risk group for developing encephalitis, do remember to wear long-sleeve shirts and pants and to generously applying DEET-containing mosquito spray—this could save your life.
Vaccines on the horizon? Dr. Carolyn Gould and her CDC colleagues published an article in the April 23, 2023 New England Journal of Medicine, “Combatting West Nile Virus Disease—Time to Revisit Vaccination” calling for vaccine development. According to a subsequent article in Healio’s Infectious Disease News on August 31, 2023, “Experts revive interest in vaccines for West Nile virus amid ongoing threat,” several vaccine candidates look promising.
The challenges ahead for developing a vaccine are formidable. But the science is there. This is best demonstrated by the incredibly successful development of the COVID-19 mRNA vaccines. Perhaps once the general public is made aware of the serious toll WNV has on both humans and other animals, the funds will follow to establish public-private partnerships for the development of a WNV vaccine. I certainly hope so.
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