“Although USUV appears less threatening than other emerging arboviruses, the association between the virus and neurological disease in humans is worrisome, and the progress of the problem cannot be underestimated.”
- Heba H. Mostafa, M.B.B.Ch, Ph.D., Associate Professor of Pathology, Johns Hopkins School of Medicine
“Methods for predicting the future: 1) read horoscopes, tea leaves, tarot cards, or crystal balls . . . collectively known as "nutty methods;" 2) put well-researched facts into sophisticated computer . . . commonly referred to as "a complete waste of time."
- Scott Adams, American author and cartoonist
Usutu virus (USUV) is a mosquito-borne virus that, like West Nile virus (WNV), is devastating wild bird populations and causing brain infections (encephalitis) in humans. USUV has yet to make its way to the U.S., but it’s on our doorstep. It is the subject of this week’s Germ Gems post.
What is USUV? USUV is an emerging arbovirus. Its name is derived from the Usutu River in Swaziland, in Southern Africa where scientists first isolated the virus in 1959.
USUV is a RNA flavivirus that is maintained in the environment through an enzootic cycle involving mosquitoes and birds. Flaviviruses include some of the most pathogenic viruses for humans including WNV, dengue virus, yellow fever virus, Zika virus as well as Japanese encephalitis virus
USUV is closely related to WNV, another mosquito-borne flavivirus that is transmitted between bird hosts by mosquito vectors. (WNV was the subject of my September 20, 2023 Germ Gems post, “America: Get West Nile Virus on Your Radar Screen.”) Mosquitoes of the Culex genus are the main vectors for both viruses. Both viruses infect bird species; USUV has been shown to infect 58 bird species, whereas WNV infects over 250 species of birds. And, humans are dead-end hosts for both viruses which means we don’t serve as a reservoir of the virus.
WNV circulates mainly in Southern Europe and the U.S. In 2023, the U.S. recorded 2,406 cases of WNV. No human cases of USUV infection have been identified in the U.S. But USUV infection has been reported from mosquitoes, birds, or horses as endemic in 12 European countries.
Central nervous system (CNS) disorders have been reported in USUV-infected birds. In the 46 documented human cases of USUV in Europe, CNS and neuroinvasive infections (encephalitis) were the major clinical manifestation of the infection. (Surveillance of blood samples from European countries suggest, however, that asymptomatic USUV infections occur more frequently than CNS disease.)
Sadly, just like for WNV infections, no antiviral agents exist that combat USUV. But, as I mentioned in my September 2023 Germ Gems post on WNV, a New England Journal of Medicine article in 2023 reported the development of a promising vaccine against WNV. And an upcoming article in Vaccine, “Development of a live-attenuated chimeric vaccine against the emerging Usutu virus,” indicates that Chinese researchers have developed a vaccine against USUV. We will have to wait to see if either of these vaccines come to fruition. In the meantime, the only treatment for both WNV and USUV is supportive care.
Predicting the arrival of USUV or another pandemic virus in the U.S. We are not even a quarter of the way through the 21st century, yet have already witnessed over a dozen pandemics, i.e., epidemics that occur worldwide involving many countries and affecting large populations, caused by emerging viruses. Nobody can accurately predict what pathogen may emerge next to wreak havoc on our species.
For example, prior to 1999, WNV had been circulating in birds and causing serious and sometimes fatal CNS disease in humans elsewhere but had not made its way to the U.S. Then in the summer of 1999, Tracey McNamarra, chief pathologist at the Bronx Zoo, first identified WNV in dead crows and flamingoes on the grounds of the zoo and made the connection to cases of encephalitis in the neighboring borough of the Queens.
How WNV got here is still unknown. It could have come via an infected migratory bird or as a stowaway infected mosquito on a flight from abroad. But what is known is how rapidly WNV spread across the continental U.S. where it became the most common cause of mosquito-borne disease (in humans and birds). And from what I’ve read about USUV, it’s only a matter of time before this virus makes its way to our shores.
We are better prepared now than we were in 1999 to deal with emerging pathogens. Because of COVID-19—an unrelated but much more devasting viral pandemic— an infrastructure is now in place in the U.S. and around the world dedicated to preparing for the next pandemics. (See, for example, the October 2023 Journal of Infectious Diseases Supplement, “Pandemic Preparedness at NIAID: Prototype Pathogen Approach to Accelerate Medical Countermeasures—Vaccines and Monoclonal Antibodies.”) But as far as I know, no one predicted the cause of any of the myriad of pandemics that emerged in the history of our species. Until that can be done, the fact is we can never be fully prepared.
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