Consider Neuroinvasive Arboviruses in Differential Dx, CDC Says

Janis C. Kelly

October 26, 2018

Arboviral infections, which are spread by mosquitos and ticks, are predominantly caused by West Nile virus in the United States. But in 2017, other arboviruses caused sporadic cases, and most were neuroinvasive, researchers from the Centers for Disease Control and Prevention (CDC) report.

The agency advises clinicians to consider arboviral infections in the differential diagnosis of aseptic meningitis and encephalitis and to obtain appropriate specimens for laboratory testing.

In 2017, there were 2291 cases of domestically acquired arboviral disease reported in 48 states and the District of Columbia, write Emily J. Curren, DVM, and colleagues in an article published October 19 Morbidity and Mortality Weekly Report. The researchers excluded cases of Dengue, chikungunya, and Zika virus infections because US patients acquire them primarily through travel.

There were 2097 confirmed or probable cases of West Nile virus infection (92% of the total reported arboviral infections), 75 cases of Jamestown Canyon virus infection, 63 cases of La Crosse virus infection, 34 cases of Powassan virus infection, 11 cases of St. Louis encephalitis, five cases of eastern equine encephalitis, and six cases of infections by unspecified California serogroups.

Neuroinvasive infections (meningitis, encephalitis, or acute flaccid paralysis) included 68% of West Nile virus infections, 77% of Jamestown Canyon virus infections, all the cases of La Crosse virus infections, 97% of Powasson virus cases, and all five of the eastern equine encephalitis cases.

Kristy Murray, DVM, PhD, who was not involved in the study, told Medscape Medical News that the rate of neuroinvasive arbovirus cases has remained generally stable but that the report from 2017 shows more cases of Jamestown Canyon and Powassan virus disease than seen before.

"Jamestown Canyon was also identified in states where it had never before been reported," Murray said. "The question remains: is this truly emerging and this increase in cases real, or are we just getting better at identifying these cases diagnostically?" Murray is professor of pediatric tropical medicine and molecular virology and microbiology and is the vice chair for research in the Department of Pediatrics at Baylor College of Medicine and Texas Children's Hospital, Houston.

"Our neuroinvasive disease cases sharply increased in 2012 and have been steady ever since then, with around 2000 cases reported each year. However, in Houston, we found that only 37% of people with viral encephalitis or meningitis are tested for West Nile during transmission season, so it is very likely that we are not capturing all neuroinvasive disease cases," Murray continued. "For every neuroinvasive disease case, we can roughly estimate that 150 others were infected with the virus, with around 20% of those presenting with an uncomplicated febrile illness. If this held true in 2017, then more than 213,000 people were infected with West Nile during this year. We have a paper currently in press in the journal Emerging Infectious Diseases that found that approximately 7 million Americans have been infected with West Nile between 1999 and 2016."

The CDC analysis also showed that West Nile virus, Jamestown Canyon virus, and St. Louis encephalitis affected predominantly male patients whose median age was 58 to 63 years. Murray said, "We are not sure if, biologically, men are at higher risk, or if it is simply related to greater outdoor exposures and being less likely to use mosquito repellents, but we consistently see this phenomenon."

Mosquito-borne La Crosse virus was the most common cause of neuroinvasive disease in children. Cases were seen in 10 states in the Southeast and Midwest; the median age of patients was 8 years.

Three of the five cases of eastern equine encephalitis were transmitted via infected organ transplants. Of those patients, two died.

Murray said, "The three cases of eastern equine encephalitis virus disease spread through organ transplantation are a really important finding. We consider eastern equine encephalitis infection to be incredibly rare, and to have transmission occur during transplant, even more so. It would have been helpful to know more about the circumstances surrounding the donor. Were they symptomatic and did they present with encephalitis? This has been seen numerous times with West Nile, and we have seen this before with rabies, where the donor died from encephalitis and the recipients developed fatal rabies infections as a result. It certainly raises important questions around the clinical presentation and screening process of donor organs for pathogens."

The CDC report emphasizes that, because there are no human vaccines against domestic arboviruses, "prevention depends on community and household efforts to reduce vector populations (eg, applying insecticides and reducing breeding sites), personal protective measures to decrease exposure to mosquitoes and ticks (eg, use of repellents and wearing protective clothing), and blood donor screening."

With regard to differential diagnosis, Murray said, "All clinical laboratories in the US should have the capacity to test for these pathogens, and these tests are available through commercial laboratories. Diagnostics are primarily focused on detecting IgM antibodies to these pathogens, since PCR [polymerase chain reaction] can often be negative by the time the patient presents with symptoms. Serum can also be submitted for testing if CSF [cerebrospinal fluid] is unavailable. IgM is typically positive within a day or two of symptom onset. IgG becomes positive 2 to 3 weeks later. If the person has neuroinvasive disease, then the optimal specimen to submit for arboviral testing is CSF.

"Often, I hear physicians ponder the importance of testing, since there is nothing that can be done for these cases therapeutically besides supportive care," Murray continued. "I argue that it's very important to test and identify cases and report them to public health authorities so that they can implement appropriate control measures and prevent others from becoming infected."

The authors and Dr Murray have disclosed report no relevant financial relationships.

MMWR Morb Mortal Wkly Rep. 2018;67:1137-1142. Full text

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