Is West Nile Virus now a neglected tropical disease?

A micrograph of the West Nile Virus, appearing in yellow.
A micrograph of the West Nile Virus, appearing in yellow. Image: Cynthia Goldsmith, P.E. Rollin, USCDCP, public domain

Scientists have characterized West Nile Virus, which can infect horses and humans, as a neglected tropical disease, noting that funding and research have declined in recent years.

This, they said, was despite the significant cost of the disease in terms of illness and deaths each year.

West Nile virus was first discovered in Uganda in 1937, and for more than 60 years circulated in animals in a mosquito-borne transmission cycle throughout Africa, the Middle East, Russia, and Europe. Infections were typically subclinical or caused a mild fever.

In the mid-1990s, a new strain emerged that resulted in a high proportion of neurological infections, with outbreaks occurring in animals in Romania, other parts of Europe, Russia, and Israel.

In late August of 1999, two cases of encephalitis — brain inflammation — were reported to the New York City Department of Health and Mental Hygiene by an infectious disease physician, Dr Deborah Asnis, prompting an investigation.

Similar cases were also quickly identified at neighboring hospitals, with West Nile Virus subsequently identified. The virus quickly went on to spread throughout North America, despite initial uncertainty over the virus’s ability to overwinter and disperse to new areas.

By 2012, all 48 continental states and the District of Columbia had reported a locally acquired human case.

Researchers Shannon Ronca, Jeanne Ruff and Kristy Murray, all with the Baylor College of Medicine and Texas Children’s Hospital in Houston, undertook a 20-year historical review of West Nile virus since its initial emergence in North America.

Since its introduction to the continent, it has become endemic, with sporadic outbreaks among animals.

Concerns about the economic impact of the infection in horses led to the licensing of an equine vaccine in the early 2000s, but few advances regarding human vaccines or treatments have since been made.

“There is a high level of virus transmission in hot/humid, subtropical climates, and high morbidity that may disproportionately affect vulnerable populations including the homeless, elderly, and those with underlying health conditions,” the trio wrote in the journal, PLOS Neglected Tropical Diseases.

“Although West Nile Virus continues to cause significant morbidity and mortality at great cost, funding and research have declined in recent years.

“These factors,” they said, “combined with neglect by policymakers and amenability of control measures, indicate that West Nile Virus has become a neglected tropical disease.”

Over the 20-year existence of the virus in the US (between 1999 and 2019), a total of 51,702 cases of West Nile virus in humans have been reported to the Centers for Disease Control’s ArboNET, including 25,227 with neuroinvasive disease, and 2376 deaths. It is likely that there have been nearly 7 million infections in the US to date, the review team said.

“Understanding the true burden of West Nile Virus is critical,” they said. “Certain populations are especially vulnerable to infection, including the homeless and others affected by socioeconomic determinants, and severe disease, including the elderly and those with underlying medical conditions.”

The authors said West Nile Virus exacts a costly toll each year in terms of illness and death, as well as the medical and economic burden. “Yet vaccine and therapeutic developments have progressed slowly in the 20 years since West Nile Virus first arrived in the US.

“Although an equine vaccine was approved shortly thereafter and has shown great success in almost eliminating equine cases and reducing risk of death by more than 40%, no human vaccine trials have proceeded past Phase II.”

Similarly, few clinical trials have tested therapeutic agents, and treatment is limited to supportive care.

“West Nile Virus may no longer be considered a novel or emerging pathogen in the US,” they said, “but its clinical and public health significance has not diminished.”

The disease, they said, has been inadequately addressed by clinicians, researchers, and policymakers. Future priorities should include research and product development for vaccines and therapeutics.

Ronca SE, Ruff JC, Murray KO (2021) A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease? PLoS Negl Trop Dis 15(5): e0009190.

The review, published under a Creative Commons License, can be read here

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