Predicting Disease Severity and Assessing Long-Term Outcomes of Pediatric La Crosse Virus

Predicting Disease Severity and Assessing Long-Term Outcomes of Pediatric La Crosse Virus 1024 683 JoAnna Pendergrass, DVM

Limited data exist on mosquito-borne La Crosse Virus in children, underscoring the importance of determining which patients are at risk for severe disease and long-term neurobehavioral difficulties.


La Crosse Virus (LACV) is a neuroinvasive arbovirus spread by the Aedes triseriatus mosquito, causing symptoms such as vomiting, seizures and altered mental status (AMS). Within the United States, it is the most common neuroinvasive arbovirus in children.

To date, sparse data exist on the long-term neurobehavioral outcomes from pediatric LACV disease, with limited data on predictors of disease severity and neurologic sequelae.

In the largest study yet of pediatric LACV disease, Christopher Ouellette, MD, a member of the Section of Infectious Diseases and Host Defense Program at Nationwide Children’s Hospital, and his research team conducted a retrospective study and analysis of long-term outcomes in children with LACV infection. Their results, which identified predictors of severe LACV and long-term disease outcomes, were recently published in Clinical Infectious Diseases.

Dr. Ouellette emphasizes the study’s collaborative effort between the infectious disease, neurology and neuropsychology departments at Nationwide Children’s. “These groups’ support was paramount to the study’s development and implementation,” he says.

The retrospective study included 152 children aged 0-18 years with proven or probable LACV, according to the Centers for Disease Control and Prevention criteria. Patients were evaluated and treated from January 2009 to December 2018 at Nationwide Children’s.

Retrospective data included demographic information and diagnostic test results (serology, neuroimaging and electroencephalography (EEG)). Several factors, such as clinical or status epilepticus and ICU admission, were used to classify patients as having severe LACV.

Of the 152 children, 65 had severe LACV. Seizures and AMS at presentation were significantly and independently associated with severe disease.

“Seizures and AMS are easily identifiable exam findings that a clinician can use to determine if a patient may have a more challenging disease course,” Dr. Ouellette explains.

Epileptiform discharges on EEG were associated with a diagnosis of epilepsy at follow-up.

To assess long-term neurobehavioral outcomes, the research team sent parent-report questionnaires to families of patients (n=113) with a previous LACV diagnosis. Questionnaires included the Pediatric Quality of Life Inventory and Child Behavior Checklist.

Questionnaires were completed for 54/113 patients (48%). The team observed a higher-than-expected rate of neurobehavioral issues, with most issues being emotionally related. This high rate suggests a lack of assessment and reporting of long-term neurobehavioral outcomes in children with LACV, potentially leading to negative educational consequences.

Learning difficulties can be a sequela of LACV and misperceived as behavioral problems, putting affected patients at risk of being left behind in school.

“We hope to identify patients at risk of neurobehavioral issues earlier and continue to follow up with them. Patients’ baseline data can then be used to help guide families’ expectations and ensure that patients receive additional educational support as needed,” he says.

Dr. Ouellette’s future research plans include studying the immune response of LACV to determine why affected patients respond differently to the infection (e.g., minor headache versus severe disease). This immunologic information could lead to developing new treatment options and identifying patients at the highest risk for severe disease.


Boutzoukas AE, Freedman DA, Koterba C, Hunt WG, Mack K, Cass J, Yildiz VO, do Los Reyes E, Twanow J, Chung MG, Ouellette CP. La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Analysis of Clinical/Neurobehavioral Outcomes and Predictors of Disease Severity. Clinical Infectious Disease. 2022 May 24. [Online ahead of print]

About the author

JoAnna Pendergrass, DVM, is a veterinarian and freelance medical writer in Atlanta, GA. She received her veterinary degree from the Virginia-Maryland College of Veterinary Medicine and completed a 2-year postdoctoral research fellowship at Emory University’s Yerkes Primate Research Center before beginning her career as a medical writer.

As a freelance medical writer, Dr. Pendergrass focuses on pet owner education and health journalism. She is a member of the American Medical Writers Association and has served as secretary and president of AMWA’s Southeast chapter.

In her spare time, Dr. Pendergrass enjoys baking, running, and playing the viola in a local community orchestra.