Feature

Decades later, still no vaccine or treatment for West Nile virus

To mark our 30th anniversary, Infectious Disease News will be examining some of the infectious diseases that have defined and changed the field over the past 3 decades.

Lyle R. Petersen

On a Monday in late August 1999, an infectious disease physician in Queens, Deborah Asnis, MD, notified the New York City health department about two hospital patients with encephalitis. Responding to her tip, investigators identified a local cluster of six more patients with similar symptoms, including five with “profound muscle weakness,” as their condition was later described in an MMWR report.

Initial testing suggested the patients had St. Louis encephalitis, a virus with symptoms that are generally mild, if they appear at all. The patients all lived in a 16-square-mile area of Queens but had little in common besides a fondness for outdoor activities near their homes in the evenings — they gardened, smoked, took walks, talked to their neighbors.

At the time city health officials announced the outbreak publicly, they began to hear about an increase in bird deaths around New York, especially among crows. Several birds at the Bronx Zoo, including two flamingoes, died, leading to a separate investigation that was not known to health officials until 4 weeks later. According to Marcelle C. Layton, MD, head of the Bureau of Communicable Diseases in the New York City health department, it was the testing of these birds that first identified West Nile virus as the virus that was circulating in both humans and birds in New York City.

It was the first time the virus had appeared in the Western Hemisphere.

The early days

It was weeks before CDC testing confirmed that the disease circulating among birds and people in New York was not St. Louis encephalitis but West Nile virus — a mosquito-borne illness first discovered in Uganda in 1937 that was not on anyone’s radar in the U.S. in 1999. According to Layton, the CDC’s finding was unexpected.

“None of us were very familiar with West Nile virus at the time, and there was little information available in the infectious disease literature in the U.S.,” Layton told Infectious Disease News.

Even before West Nile was confirmed as the cause, the outbreak provoked an effective public health response. The city established a telephone hotline to answer questions and warned the public with leaflets and public messages on the radio and TV to take precautions against mosquitoes. It distributed insect repellent at fire houses and for the first time began to spray pesticides in areas where there was evidence of West Nile activity, using aircraft in the outer boroughs and trucks in skyscraper-filled Manhattan.

“The more dead mosquitoes, the better,” then-New York City Mayor Rudolph W. Giuliani was quoted by The New York Times as saying.

Layton worked for the city health department in 1999 and received the initial phone call from Asnis, whose attentiveness was credited with preventing a larger outbreak. Layton said Asnis, who died in 2015, demonstrated how crucial it is for physicians to astutely report unusual findings to public health officials.

“If not for the first call from Dr. Asnis, this outbreak may not have been detected at all, or its recognition significantly delayed,” Layton said.

‘Makes perfect sense’

Experts believe West Nile virus probably arrived in the U.S. via an infected animal, most likely a bird. Humans do not carry enough virus to efficiently infect mosquitoes and are unlikely to be the original source, according to Lyle R. Petersen, MD, MPH,Infectious Disease News Editorial Board member and director of the CDC’s Division of Vector-Borne Diseases. Besides North America, West Nile virus is commonly found in Africa, Europe, the Middle East and West Asia. As for the strain that landed in New York, studies showed that it likely came from somewhere in North Africa.

“To have an exotic virus all of a sudden show up in the middle of a major city is a little shocking. But in retrospect, what it did was highlight the importance of travel and trade,” Petersen said in an interview. “The fact that it showed up in a place like New York City makes perfect sense. Where do people and goods go from foreign locations? To major cities.”

Overall, 59 patients were hospitalized with West Nile virus infection in the New York City area during August and September 1999, and seven died. Since then, the virus has become endemic in America, spreading to every state in the continental U.S. The virus exists in a cycle between birds and mosquitoes, especially Culex spp. Mosquitoes can infect humans, horses and other mammals.

“It is the most significant mosquito-borne illness in the U.S. by far, at this point,” Petersen said.

Despite this, there remains no medical way to prevent West Nile virus in humans or to treat infected patients. In fact, according to Petersen, in the last 18 years, no candidate vaccine and only one potential therapeutic has made it to a phase 3 clinical trial. This is not necessarily unusual for diseases spread by arthropod vectors.

“There is no vaccine or specific treatment for many other arboviruses that have been endemic here for much longer [than West Nile],” Layton said.

According to Petersen, there are several effective licensed horse vaccines and an experimental vaccine that also has been used to inoculate birds, which probably saved the California condor from extinction. But there are barriers to developing a human vaccine, he said, including the risk that manufacturers who carry a vaccine all the way to a phase 3 trial may not recoup their investment.

Moreover, Petersen said the system currently in place for conducting clinical trials is not geared toward finding potential vaccines and therapeutics for unpredictable emerging diseases. The trials are difficult to undertake given that researchers cannot tell from year to year where the diseases will pop up, making it unlikely that there will be an available vaccine in the near future.

“I can’t say never, but I don’t see one even on the horizon, simply because there’s no phase 3 clinical trials of a therapeutic or a vaccine even being contemplated,” Petersen said.”

In another watershed development, the arrival of West Nile virus in the U.S. led to the discovery that the virus could be spread by blood transfusions and organ transplantation. Because the incidence of infection is so high, the U.S. blood supply is now screened for West Nile — a first for a mosquito-borne virus, Petersen noted.

“Same with organ transplantation,” he said. “This was the first mosquito-borne virus that was shown to be spread through organ transplantation as well. It was a huge paradigm shift.”

A walk to the mailbox

One day in 2003, Petersen stepped outside his Colorado home at dusk to get his mail and stopped to have a conversation with his neighbor. He was outside longer than expected.

“I did exactly what you shouldn’t do — I went out toward the end of July right at dusk when the mosquitoes are more active,” he said.

A few days later, midway through his morning run, Petersen suddenly felt sick. He spent a week in bed with eye pain, myalgias, headache, photophobia and a stiff neck. He had horrible fatigue and a skin rash. It took him 8 or 9 days to recover.

Petersen had West Nile fever — not as severe an illness as the approximately 1 in 150 patients with West Nile virus who develop serious central nervous system complications like encephalitis and meningitis, but it was the worst illness he has ever felt.

“That was the last time I called West Nile a mild disease,” Petersen said. “I’m a long-distance runner, and I could barely walk up the stairs for months. It was horrible.”

So far in 2017, 1,502 people in 47 states have contracted West Nile virus, including 66% who were classified as having neuroinvasive disease, according to preliminary CDC statistics. Petersen said somewhere between 500 and 2,000 people who contract West Nile virus each year develop severe disease. Around 10% of them die and many more are left with permanent neurological problems.

Physicians can order tests for patients with suspected West Nile virus, but treatment options are limited. According to the CDC, over-the-counter pain relievers can be used to reduce fever and relieve some symptoms. For patients with more serious disease, hospitalization and treatment with IV fluids and pain medication may be necessary.

“Fortunately, I recovered completely,” Petersen said, “but a lot of people don’t.” – by Gerard Gallagher

Disclosures: Layton and Petersen report no relevant financial disclosures.

To mark our 30th anniversary, Infectious Disease News will be examining some of the infectious diseases that have defined and changed the field over the past 3 decades.

Lyle R. Petersen

On a Monday in late August 1999, an infectious disease physician in Queens, Deborah Asnis, MD, notified the New York City health department about two hospital patients with encephalitis. Responding to her tip, investigators identified a local cluster of six more patients with similar symptoms, including five with “profound muscle weakness,” as their condition was later described in an MMWR report.

Initial testing suggested the patients had St. Louis encephalitis, a virus with symptoms that are generally mild, if they appear at all. The patients all lived in a 16-square-mile area of Queens but had little in common besides a fondness for outdoor activities near their homes in the evenings — they gardened, smoked, took walks, talked to their neighbors.

At the time city health officials announced the outbreak publicly, they began to hear about an increase in bird deaths around New York, especially among crows. Several birds at the Bronx Zoo, including two flamingoes, died, leading to a separate investigation that was not known to health officials until 4 weeks later. According to Marcelle C. Layton, MD, head of the Bureau of Communicable Diseases in the New York City health department, it was the testing of these birds that first identified West Nile virus as the virus that was circulating in both humans and birds in New York City.

It was the first time the virus had appeared in the Western Hemisphere.

The early days

It was weeks before CDC testing confirmed that the disease circulating among birds and people in New York was not St. Louis encephalitis but West Nile virus — a mosquito-borne illness first discovered in Uganda in 1937 that was not on anyone’s radar in the U.S. in 1999. According to Layton, the CDC’s finding was unexpected.

“None of us were very familiar with West Nile virus at the time, and there was little information available in the infectious disease literature in the U.S.,” Layton told Infectious Disease News.

Even before West Nile was confirmed as the cause, the outbreak provoked an effective public health response. The city established a telephone hotline to answer questions and warned the public with leaflets and public messages on the radio and TV to take precautions against mosquitoes. It distributed insect repellent at fire houses and for the first time began to spray pesticides in areas where there was evidence of West Nile activity, using aircraft in the outer boroughs and trucks in skyscraper-filled Manhattan.

PAGE BREAK

“The more dead mosquitoes, the better,” then-New York City Mayor Rudolph W. Giuliani was quoted by The New York Times as saying.

Layton worked for the city health department in 1999 and received the initial phone call from Asnis, whose attentiveness was credited with preventing a larger outbreak. Layton said Asnis, who died in 2015, demonstrated how crucial it is for physicians to astutely report unusual findings to public health officials.

“If not for the first call from Dr. Asnis, this outbreak may not have been detected at all, or its recognition significantly delayed,” Layton said.

‘Makes perfect sense’

Experts believe West Nile virus probably arrived in the U.S. via an infected animal, most likely a bird. Humans do not carry enough virus to efficiently infect mosquitoes and are unlikely to be the original source, according to Lyle R. Petersen, MD, MPH,Infectious Disease News Editorial Board member and director of the CDC’s Division of Vector-Borne Diseases. Besides North America, West Nile virus is commonly found in Africa, Europe, the Middle East and West Asia. As for the strain that landed in New York, studies showed that it likely came from somewhere in North Africa.

“To have an exotic virus all of a sudden show up in the middle of a major city is a little shocking. But in retrospect, what it did was highlight the importance of travel and trade,” Petersen said in an interview. “The fact that it showed up in a place like New York City makes perfect sense. Where do people and goods go from foreign locations? To major cities.”

Overall, 59 patients were hospitalized with West Nile virus infection in the New York City area during August and September 1999, and seven died. Since then, the virus has become endemic in America, spreading to every state in the continental U.S. The virus exists in a cycle between birds and mosquitoes, especially Culex spp. Mosquitoes can infect humans, horses and other mammals.

“It is the most significant mosquito-borne illness in the U.S. by far, at this point,” Petersen said.

Despite this, there remains no medical way to prevent West Nile virus in humans or to treat infected patients. In fact, according to Petersen, in the last 18 years, no candidate vaccine and only one potential therapeutic has made it to a phase 3 clinical trial. This is not necessarily unusual for diseases spread by arthropod vectors.

“There is no vaccine or specific treatment for many other arboviruses that have been endemic here for much longer [than West Nile],” Layton said.

PAGE BREAK

According to Petersen, there are several effective licensed horse vaccines and an experimental vaccine that also has been used to inoculate birds, which probably saved the California condor from extinction. But there are barriers to developing a human vaccine, he said, including the risk that manufacturers who carry a vaccine all the way to a phase 3 trial may not recoup their investment.

Moreover, Petersen said the system currently in place for conducting clinical trials is not geared toward finding potential vaccines and therapeutics for unpredictable emerging diseases. The trials are difficult to undertake given that researchers cannot tell from year to year where the diseases will pop up, making it unlikely that there will be an available vaccine in the near future.

“I can’t say never, but I don’t see one even on the horizon, simply because there’s no phase 3 clinical trials of a therapeutic or a vaccine even being contemplated,” Petersen said.”

In another watershed development, the arrival of West Nile virus in the U.S. led to the discovery that the virus could be spread by blood transfusions and organ transplantation. Because the incidence of infection is so high, the U.S. blood supply is now screened for West Nile — a first for a mosquito-borne virus, Petersen noted.

“Same with organ transplantation,” he said. “This was the first mosquito-borne virus that was shown to be spread through organ transplantation as well. It was a huge paradigm shift.”

A walk to the mailbox

One day in 2003, Petersen stepped outside his Colorado home at dusk to get his mail and stopped to have a conversation with his neighbor. He was outside longer than expected.

“I did exactly what you shouldn’t do — I went out toward the end of July right at dusk when the mosquitoes are more active,” he said.

A few days later, midway through his morning run, Petersen suddenly felt sick. He spent a week in bed with eye pain, myalgias, headache, photophobia and a stiff neck. He had horrible fatigue and a skin rash. It took him 8 or 9 days to recover.

Petersen had West Nile fever — not as severe an illness as the approximately 1 in 150 patients with West Nile virus who develop serious central nervous system complications like encephalitis and meningitis, but it was the worst illness he has ever felt.

“That was the last time I called West Nile a mild disease,” Petersen said. “I’m a long-distance runner, and I could barely walk up the stairs for months. It was horrible.”

So far in 2017, 1,502 people in 47 states have contracted West Nile virus, including 66% who were classified as having neuroinvasive disease, according to preliminary CDC statistics. Petersen said somewhere between 500 and 2,000 people who contract West Nile virus each year develop severe disease. Around 10% of them die and many more are left with permanent neurological problems.

Physicians can order tests for patients with suspected West Nile virus, but treatment options are limited. According to the CDC, over-the-counter pain relievers can be used to reduce fever and relieve some symptoms. For patients with more serious disease, hospitalization and treatment with IV fluids and pain medication may be necessary.

“Fortunately, I recovered completely,” Petersen said, “but a lot of people don’t.” – by Gerard Gallagher

Disclosures: Layton and Petersen report no relevant financial disclosures.

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