Encephalitis

Our group is working to use pediatric clinical data to develop a prediction tool that physicians can use to distinguish between autoimmune and infectious encephalitis. When a patient presents to the hospital with encephalitis, it is often difficult to quickly determine the cause of their illness. Confirmatory testing can take weeks, and physicians need to act before receiving these results. Unfortunately, the treatment strategies for these two etiological buckets are opposite, and it can be dangerous to treat for the wrong cause. We are using clinical data from pediatric patients with encephalitis across multiple health systems to develop an algorithm to distinguish between autoimmune and infectious causes of encephalitis when patients present to the health facility. We hope to provide this as a tool to help with clinical decision-making and improve outcomes for children with encephalitis.

Selected Publications: 

• Erickson TA, Muscal E, Munoz FM, Lotze T, Hasbun R, Brown E, Murray KO. Infectious and Autoimmune Causes of Encephalitis in Children. Pediatrics. 2020 Jun;145(6):e20192543. doi: 10.1542/peds.2019-2543. Epub 2020 May 1. PMID: 32358069. 
• Sandweiss AJ, Erickson TA, Jiang Y, Kannan V, Yarimi JM, Levine JM, Fisher K, Muscal E, Demmler-Harrison G, Murray KO, Ronca SE. Infectious profiles in pediatric anti-N-methyl-d-aspartate receptor encephalitis. J Neuroimmunol. 2023 Aug 15;381:578139. doi: 10.1016/j.jneuroim.2023.578139. Epub 2023 Jun 20. PMID: 37364517. 
• Gombolay G, Brenton JN, Yang JH, Stredny CM, Kammeyer R, Fisher KS, Sandweiss AJ, Erickson TA, Kannan V, Otten C, Steriade C, Vu N, Santoro JD, Robles-Lopez K, Goodrich R, Otallah S, Arellano J, Christiana A, Morris M, Gorman MP, Kornbluh AB, Kahn I, Sepeta L, Jiang Y, Muscal E, Murray KO, Moodley M, Hardy D. Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis. Pediatr Neurol. 2024 Oct;159:12-15. doi: 10.1016/j.pediatrneurol.2024.07.009. Epub 2024 Jul 17. PMID: 39094249; PMCID: PMC11381152. 
• Erickson TA, Munoz FM, Troisi CL, Nolan MS, Hasbun R, Brown EL, Murray KO. The Epidemiology of Meningitis in Infants under 90 Days of Age in a Large Pediatric Hospital. Microorganisms. 2021 Mar 4;9(3):526. doi: 10.3390/microorganisms9030526.. PMID: 33806478 PMCID: PMC7999219 doi:10.3390/microorganisms9030526

Infectious encephalitis can result from infection by pathogens of all types — bacteria, viruses, parasites, and fungi — but viruses are the primary cause, accounting for ~70% of all confirmed encephalitis cases. Among these, West Nile virus (WNV) is a major concern: it is the leading mosquito-borne illness in the contiguous United States, with an estimated 7 million infections since the initial outbreak in New York in 1999. About 1 in 150 cases progress to West Nile neuroinvasive disease (WNND), a severe condition involving meningitis, encephalitis, or acute flaccid paralysis with ~10% mortality. We maintain a biorepository from the longest longitudinal cohort of confirmed West Nile cases. From this cohort, we have established that WNND survivors often suffer lasting neurological deficits: 60% remain symptomatic one year post-infection, and >85% report impaired quality of life. Despite its significant burden, no specific treatment exists beyond supportive care.

Our objective is to advance WNV therapy through a multi-pronged approach targeting both drug development and neuropathogenesis. We apply traditional virology and modern systems biology approaches, including tissue culture, plaque assays, qPCR/dPCR, transcriptomics, in vivo models, protein biochemistry, and high-throughput drug screening to uncover disease mechanisms and identify therapeutic candidates.

Selected Publications: 

• Nash D, Mostashari F, Fine A, Miller J, O'Leary D, Murray K, Huang A, Rosenberg A, Greenberg A, Sherman M, Wong S, Layton M; 1999 West Nile Outbreak Response Working Group. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med. 2001 Jun 14;344(24):1807-14. doi: 10.1056/NEJM200106143442401. PMID: 11407341. 
• Murray K, Walker C, Herrington E, Lewis JA, McCormick J, Beasley DW, Tesh RB, Fisher-Hoch S. Persistent infection with West Nile virus years after initial infection. J Infect Dis. 2010 Jan 1;201(1):2-4. doi: 10.1086/648731. PMID: 19961306; PMCID: PMC2791189. 
• Murray KO, Mertens E, Despres P. West Nile virus and its emergence in the United States of America. Vet Res. 2010 Nov-Dec;41(6):67. doi: 10.1051/vetres/2010039. PMID: 21188801; PMCID: PMC2913730. 
• Murray K, Baraniuk S, Resnick M, Arafat R, Kilborn C, Cain K, Shallenberger R, York TL, Martinez D, Hellums JS, Hellums D, Malkoff M, Elgawley N, McNeely W, Khuwaja SA, Tesh RB. Risk factors for encephalitis and death from West Nile virus infection. Epidemiol Infect. 2006 Dec;134(6):1325-32. doi: 10.1017/S0950268806006339. Epub 2006 May 4. PMID: 16672108; PMCID: PMC2870518. 
• Ronca SE, Ruff JC, Murray KO. 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. 2021 May 6;15(5):e0009190. doi: 10.1371/journal.pntd.0009190. PMID: 33956816; PMCID: PMC8101735. 
• Bigham AW, Buckingham KJ, Husain S, Emond MJ, Bofferding KM, Gildersleeve H, Rutherford A, Astakhova NM, Perelygin AA, Busch MP, Murray KO, Sejvar JJ, Green S, Kriesel J, Brinton MA, Bamshad M. Host genetic risk factors for West Nile virus infection and disease progression. PLoS One. 2011;6(9):e24745. doi: 10.1371/journal.pone.0024745. Epub 2011 Sep 15. PMID: 21935451; PMCID: PMC3174177. 
• Weatherhead JE, Miller VE, Garcia MN, Hasbun R, Salazar L, Dimachkie MM, Murray KO. Long-term neurological outcomes in West Nile virus-infected patients: an observational study. Am J Trop Med Hyg. 2015 May;92(5):1006-1012. doi: 10.4269/ajtmh.14-0616. Epub 2015 Mar 23. PMID: 25802426; PMCID: PMC4426557. 
• Murray KO, Garcia MN, Rahbar MH, Martinez D, Khuwaja SA, Arafat RR, Rossmann S. Survival analysis, long-term outcomes, and percentage of recovery up to 8 years post-infection among the Houston West Nile virus cohort. PLoS One. 2014 Jul 23;9(7):e102953. doi: 10.1371/journal.pone.0102953. PMID: 25054656; PMCID: PMC4108377. 
• Murray KO, Walker C, Gould E. The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere. Epidemiol Infect. 2011 Jun;139(6):807-17. doi: 10.1017/S0950268811000185. Epub 2011 Feb 23. PMID: 21342610. 
• Nolan MS, Podoll AS, Hause AM, Akers KM, Finkel KW, Murray KO. Prevalence of chronic kidney disease and progression of disease over time among patients enrolled in the Houston West Nile virus cohort. PLoS One. 2012;7(7):e40374. doi: 10.1371/journal.pone.0040374. Epub 2012 Jul 6. PMID: 22792293; PMCID: PMC3391259.