Arboviral Disease Season: It's On!

VAIL, COLO. – The number one cause of pediatric neuroinvasive arboviral disease in the United States turns out to be – to the surprise of most physicians – La Crosse virus.

That’s right. Not West Nile, but La Crosse.

West Nile infections draw most of the national attention and fear, and rightfully so. A total of 10,237 cases of West Nile meningitis, encephalitis, or myelitis in children and adults were reported to ArboNET, the Centers for Disease Control and Prevention’s (CDC’s) national surveillance system, between 2003 and 2011. That’s over 10 times more than the combined number of reported cases of neuroinvasive disease caused by the other arthropod-borne viruses or arboviruses: La Crosse virus, eastern equine encephalitis virus, St. Louis encephalitis virus, and Powassan virus, Dr. Marc Fischer said at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

Copyright CDC

Cases of neuroinvasive La Crosse virus disease outnumber West Nile virus disease in the pediatric age group because the age distribution of the infections is dramatically different. While fully 88% of all cases of neuroinvasive disease caused by La Crosse virus occurred in patients under age 18, that was true for only 4% of cases of West Nile neuroinvasive disease, noted Dr. Fischer, a medical epidemiologist at the CDC’s Arboviral Disease Branch in Fort Collins, Colo.

This translates to an average annual incidence of 0.9 cases of La Crosse virus neuroinvasive disease per million U.S. children and adolescents for 2003-2011, compared with 0.63 cases per million for West Nile virus. Trailing far behind are eastern equine encephalitis virus at 0.04 per million, followed by Powassan virus and St. Louis encephalitis virus, tied at 0.01 cases of neuroinvasive disease per million individuals under age 18, he reported.

These incidence figures greatly underestimate the actual risk of these diseases in regions where the arboviruses are endemic. La Crosse virus, for example, is extremely focal in its distribution. During 2003-2011, more than 80% of all cases of La Crosse virus pediatric neuroinvasive disease were reported from four states: Ohio, West Virginia, North Carolina, and Tennessee.

"These are the states where you really need to be thinking about La Crosse virus when you have a child with meningitis or encephalitis," Dr. Fischer said.

In contrast to the other disease-causing arboviruses, West Nile virus is endemic all across the country. Yet it, too, is focal in its distribution. While cases of West Nile virus pediatric neuroinvasive disease were reported from nearly every state during 2003-2011, those cases occurred in only about 8% of the more than 3,000 U.S. counties in the continental United States.

Nationally, the annual incidence of both West Nile and La Crosse virus pediatric neuroinvasive disease dropped steadily through 2007 from a peak in 2003. Since 2007, however, reported La Crosse virus disease cases have increased, while West Nile cases have continued to drop. However, in 2012 there have been more reported cases of West Nile virus neuroinvasive disease to date than on the same date in any year since 2004, with most of the activity being concentrated in Texas, Oklahoma, and Mississippi, according to Dr. Fischer.

The clinical syndrome of pediatric arboviral disease tends to be expressed differently depending upon whether the infectious agent is La Crosse or West Nile virus. In all, 78% of La Crosse cases reported to ArboNET in 2003-2011 were classified as encephalitis and 20% were meningitis, while West Nile virus cases were split 47% encephalitis and 50% meningitis.

The most lethal pediatric neuroinvasive arboviral disease is eastern equine encephalitis virus infection, with a 38% mortality rate. It’s such a rare disease, however, that this very high mortality rate translated to only 26 deaths nationwide in 2003-2011. The mortality rate was just 1% each for La Crosse and West Nile virus pediatric neuroinvasive disease.

The clinical spectrum of most domestic arboviral infections follows the same general pattern: 70%-80% of infections are asymptomatic, 20%-30% result in a generally self-limited, systemic, flulike febrile illness, and less than 1% of infections result in neuroinvasive disease.

Diagnostic laboratory testing for suspected neuroinvasive arboviral disease entails testing for IgM antibodies in the serum or cerebrospinal fluid (CSF), then confirmatory testing for neutralizing antibodies. Commercial IgM antibody assays for West Nile virus are readily available. Physicians have three options for testing for the other arboviruses: a commercially available immunofluorescent assay kit marketed by Focus Diagnostics; most state health departments will perform testing; and the CDC accepts specimens for testing at its Fort Collins laboratory.

Diagnostic testing of CSF offers two advantages over serologic testing. One is that if testing is done early – say, 4-5 days after illness onset – IgM antibodies may not be present yet in serum, but they will likely be in the CSF.

"When you get out to 9 or 10 days, though, there’s not really a difference. Everybody should have IgM antibodies in their CSF and serum," Dr. Fischer explained.

The other advantage of testing the CSF is that IgM antibodies to West Nile virus can be maintained in the serum for a long time. Their presence could be due to an asymptomatic infection that occurred the previous year. In contrast, finding IgM antibodies in the CSF of a patient with neurologic symptoms boosts the likelihood that the patient has a focal viral infection.

In response to an audience question as to why West Nile virus neuroinvasive disease has been on the wane in the United States for most of the past decade, Dr. Fischer was quick to reply that no one knows. The most popular hypothesis is that it’s due to human herd immunity, but he considers that unlikely. More plausible in his view is that the vertebrate hosts of the virus – birds – have become immune in a given area.

Or there may be an entirely different and as yet unrecognized explanation, he continued. After all, western equine encephalitis virus was a not uncommon cause of neuroinvasive disease in the western and central United States between the 1960s and the early 1990s, yet for unknown reasons no cases have been reported since 1999.

"If you look back historically, St. Louis encephalitis virus infection, when it did occur more in the United States, occurred in very large outbreaks with 20- to 30-year intervals in between. The first U.S. case of West Nile disease in humans was identified in New York in 1999, so we’re really only 12 years into our West Nile outbreak. Maybe it’ll be like St. Louis encephalitis virus: quiet for 20-30 years before coming back with a big year," he said.

Dr. Fischer stressed that the views he expressed are his own and not necessarily those of the CDC. He reported having no financial conflicts.

VAIL, COLO. – The number one cause of pediatric neuroinvasive arboviral disease in the United States turns out to be – to the surprise of most physicians – La Crosse virus.

That’s right. Not West Nile, but La Crosse.

West Nile infections draw most of the national attention and fear, and rightfully so. A total of 10,237 cases of West Nile meningitis, encephalitis, or myelitis in children and adults were reported to ArboNET, the Centers for Disease Control and Prevention’s (CDC’s) national surveillance system, between 2003 and 2011. That’s over 10 times more than the combined number of reported cases of neuroinvasive disease caused by the other arthropod-borne viruses or arboviruses: La Crosse virus, eastern equine encephalitis virus, St. Louis encephalitis virus, and Powassan virus, Dr. Marc Fischer said at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

Copyright CDC

Cases of neuroinvasive La Crosse virus disease outnumber West Nile virus disease in the pediatric age group because the age distribution of the infections is dramatically different. While fully 88% of all cases of neuroinvasive disease caused by La Crosse virus occurred in patients under age 18, that was true for only 4% of cases of West Nile neuroinvasive disease, noted Dr. Fischer, a medical epidemiologist at the CDC’s Arboviral Disease Branch in Fort Collins, Colo.

This translates to an average annual incidence of 0.9 cases of La Crosse virus neuroinvasive disease per million U.S. children and adolescents for 2003-2011, compared with 0.63 cases per million for West Nile virus. Trailing far behind are eastern equine encephalitis virus at 0.04 per million, followed by Powassan virus and St. Louis encephalitis virus, tied at 0.01 cases of neuroinvasive disease per million individuals under age 18, he reported.

These incidence figures greatly underestimate the actual risk of these diseases in regions where the arboviruses are endemic. La Crosse virus, for example, is extremely focal in its distribution. During 2003-2011, more than 80% of all cases of La Crosse virus pediatric neuroinvasive disease were reported from four states: Ohio, West Virginia, North Carolina, and Tennessee.

"These are the states where you really need to be thinking about La Crosse virus when you have a child with meningitis or encephalitis," Dr. Fischer said.

In contrast to the other disease-causing arboviruses, West Nile virus is endemic all across the country. Yet it, too, is focal in its distribution. While cases of West Nile virus pediatric neuroinvasive disease were reported from nearly every state during 2003-2011, those cases occurred in only about 8% of the more than 3,000 U.S. counties in the continental United States.

Nationally, the annual incidence of both West Nile and La Crosse virus pediatric neuroinvasive disease dropped steadily through 2007 from a peak in 2003. Since 2007, however, reported La Crosse virus disease cases have increased, while West Nile cases have continued to drop. However, in 2012 there have been more reported cases of West Nile virus neuroinvasive disease to date than on the same date in any year since 2004, with most of the activity being concentrated in Texas, Oklahoma, and Mississippi, according to Dr. Fischer.

The clinical syndrome of pediatric arboviral disease tends to be expressed differently depending upon whether the infectious agent is La Crosse or West Nile virus. In all, 78% of La Crosse cases reported to ArboNET in 2003-2011 were classified as encephalitis and 20% were meningitis, while West Nile virus cases were split 47% encephalitis and 50% meningitis.

The most lethal pediatric neuroinvasive arboviral disease is eastern equine encephalitis virus infection, with a 38% mortality rate. It’s such a rare disease, however, that this very high mortality rate translated to only 26 deaths nationwide in 2003-2011. The mortality rate was just 1% each for La Crosse and West Nile virus pediatric neuroinvasive disease.

The clinical spectrum of most domestic arboviral infections follows the same general pattern: 70%-80% of infections are asymptomatic, 20%-30% result in a generally self-limited, systemic, flulike febrile illness, and less than 1% of infections result in neuroinvasive disease.

Diagnostic laboratory testing for suspected neuroinvasive arboviral disease entails testing for IgM antibodies in the serum or cerebrospinal fluid (CSF), then confirmatory testing for neutralizing antibodies. Commercial IgM antibody assays for West Nile virus are readily available. Physicians have three options for testing for the other arboviruses: a commercially available immunofluorescent assay kit marketed by Focus Diagnostics; most state health departments will perform testing; and the CDC accepts specimens for testing at its Fort Collins laboratory.

Diagnostic testing of CSF offers two advantages over serologic testing. One is that if testing is done early – say, 4-5 days after illness onset – IgM antibodies may not be present yet in serum, but they will likely be in the CSF.

"When you get out to 9 or 10 days, though, there’s not really a difference. Everybody should have IgM antibodies in their CSF and serum," Dr. Fischer explained.

The other advantage of testing the CSF is that IgM antibodies to West Nile virus can be maintained in the serum for a long time. Their presence could be due to an asymptomatic infection that occurred the previous year. In contrast, finding IgM antibodies in the CSF of a patient with neurologic symptoms boosts the likelihood that the patient has a focal viral infection.

In response to an audience question as to why West Nile virus neuroinvasive disease has been on the wane in the United States for most of the past decade, Dr. Fischer was quick to reply that no one knows. The most popular hypothesis is that it’s due to human herd immunity, but he considers that unlikely. More plausible in his view is that the vertebrate hosts of the virus – birds – have become immune in a given area.

Or there may be an entirely different and as yet unrecognized explanation, he continued. After all, western equine encephalitis virus was a not uncommon cause of neuroinvasive disease in the western and central United States between the 1960s and the early 1990s, yet for unknown reasons no cases have been reported since 1999.

"If you look back historically, St. Louis encephalitis virus infection, when it did occur more in the United States, occurred in very large outbreaks with 20- to 30-year intervals in between. The first U.S. case of West Nile disease in humans was identified in New York in 1999, so we’re really only 12 years into our West Nile outbreak. Maybe it’ll be like St. Louis encephalitis virus: quiet for 20-30 years before coming back with a big year," he said.

Dr. Fischer stressed that the views he expressed are his own and not necessarily those of the CDC. He reported having no financial conflicts.

VAIL, COLO. – The number one cause of pediatric neuroinvasive arboviral disease in the United States turns out to be – to the surprise of most physicians – La Crosse virus.

That’s right. Not West Nile, but La Crosse.

West Nile infections draw most of the national attention and fear, and rightfully so. A total of 10,237 cases of West Nile meningitis, encephalitis, or myelitis in children and adults were reported to ArboNET, the Centers for Disease Control and Prevention’s (CDC’s) national surveillance system, between 2003 and 2011. That’s over 10 times more than the combined number of reported cases of neuroinvasive disease caused by the other arthropod-borne viruses or arboviruses: La Crosse virus, eastern equine encephalitis virus, St. Louis encephalitis virus, and Powassan virus, Dr. Marc Fischer said at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

Copyright CDC

Cases of neuroinvasive La Crosse virus disease outnumber West Nile virus disease in the pediatric age group because the age distribution of the infections is dramatically different. While fully 88% of all cases of neuroinvasive disease caused by La Crosse virus occurred in patients under age 18, that was true for only 4% of cases of West Nile neuroinvasive disease, noted Dr. Fischer, a medical epidemiologist at the CDC’s Arboviral Disease Branch in Fort Collins, Colo.

This translates to an average annual incidence of 0.9 cases of La Crosse virus neuroinvasive disease per million U.S. children and adolescents for 2003-2011, compared with 0.63 cases per million for West Nile virus. Trailing far behind are eastern equine encephalitis virus at 0.04 per million, followed by Powassan virus and St. Louis encephalitis virus, tied at 0.01 cases of neuroinvasive disease per million individuals under age 18, he reported.

These incidence figures greatly underestimate the actual risk of these diseases in regions where the arboviruses are endemic. La Crosse virus, for example, is extremely focal in its distribution. During 2003-2011, more than 80% of all cases of La Crosse virus pediatric neuroinvasive disease were reported from four states: Ohio, West Virginia, North Carolina, and Tennessee.

"These are the states where you really need to be thinking about La Crosse virus when you have a child with meningitis or encephalitis," Dr. Fischer said.

In contrast to the other disease-causing arboviruses, West Nile virus is endemic all across the country. Yet it, too, is focal in its distribution. While cases of West Nile virus pediatric neuroinvasive disease were reported from nearly every state during 2003-2011, those cases occurred in only about 8% of the more than 3,000 U.S. counties in the continental United States.

Nationally, the annual incidence of both West Nile and La Crosse virus pediatric neuroinvasive disease dropped steadily through 2007 from a peak in 2003. Since 2007, however, reported La Crosse virus disease cases have increased, while West Nile cases have continued to drop. However, in 2012 there have been more reported cases of West Nile virus neuroinvasive disease to date than on the same date in any year since 2004, with most of the activity being concentrated in Texas, Oklahoma, and Mississippi, according to Dr. Fischer.

The clinical syndrome of pediatric arboviral disease tends to be expressed differently depending upon whether the infectious agent is La Crosse or West Nile virus. In all, 78% of La Crosse cases reported to ArboNET in 2003-2011 were classified as encephalitis and 20% were meningitis, while West Nile virus cases were split 47% encephalitis and 50% meningitis.

The most lethal pediatric neuroinvasive arboviral disease is eastern equine encephalitis virus infection, with a 38% mortality rate. It’s such a rare disease, however, that this very high mortality rate translated to only 26 deaths nationwide in 2003-2011. The mortality rate was just 1% each for La Crosse and West Nile virus pediatric neuroinvasive disease.

The clinical spectrum of most domestic arboviral infections follows the same general pattern: 70%-80% of infections are asymptomatic, 20%-30% result in a generally self-limited, systemic, flulike febrile illness, and less than 1% of infections result in neuroinvasive disease.

Diagnostic laboratory testing for suspected neuroinvasive arboviral disease entails testing for IgM antibodies in the serum or cerebrospinal fluid (CSF), then confirmatory testing for neutralizing antibodies. Commercial IgM antibody assays for West Nile virus are readily available. Physicians have three options for testing for the other arboviruses: a commercially available immunofluorescent assay kit marketed by Focus Diagnostics; most state health departments will perform testing; and the CDC accepts specimens for testing at its Fort Collins laboratory.

Diagnostic testing of CSF offers two advantages over serologic testing. One is that if testing is done early – say, 4-5 days after illness onset – IgM antibodies may not be present yet in serum, but they will likely be in the CSF.

"When you get out to 9 or 10 days, though, there’s not really a difference. Everybody should have IgM antibodies in their CSF and serum," Dr. Fischer explained.

The other advantage of testing the CSF is that IgM antibodies to West Nile virus can be maintained in the serum for a long time. Their presence could be due to an asymptomatic infection that occurred the previous year. In contrast, finding IgM antibodies in the CSF of a patient with neurologic symptoms boosts the likelihood that the patient has a focal viral infection.

In response to an audience question as to why West Nile virus neuroinvasive disease has been on the wane in the United States for most of the past decade, Dr. Fischer was quick to reply that no one knows. The most popular hypothesis is that it’s due to human herd immunity, but he considers that unlikely. More plausible in his view is that the vertebrate hosts of the virus – birds – have become immune in a given area.

Or there may be an entirely different and as yet unrecognized explanation, he continued. After all, western equine encephalitis virus was a not uncommon cause of neuroinvasive disease in the western and central United States between the 1960s and the early 1990s, yet for unknown reasons no cases have been reported since 1999.

"If you look back historically, St. Louis encephalitis virus infection, when it did occur more in the United States, occurred in very large outbreaks with 20- to 30-year intervals in between. The first U.S. case of West Nile disease in humans was identified in New York in 1999, so we’re really only 12 years into our West Nile outbreak. Maybe it’ll be like St. Louis encephalitis virus: quiet for 20-30 years before coming back with a big year," he said.

Dr. Fischer stressed that the views he expressed are his own and not necessarily those of the CDC. He reported having no financial conflicts.