St. Louis encephalitis
- Thomas P Monath, MD, FACP, FASTMH
Thomas P Monath, MD, FACP, FASTMH
- NewLink Genetics Corp
- Adjunct Professor (Emeritus)
- Harvard School of Public Health
St. Louis encephalitis (SLE) is an acute, mosquito-borne viral illness characterized by meningeal and brain parenchymal inflammation and injury. The disease occurs in endemic and epidemic form in North and South America. Epidemics of SLE in the United States have been responsible for at least 1,000,000 mild or subclinical infections, 10,000 clinical cases, and 1000 deaths since SLE virus was first isolated in 1933 during an outbreak in St. Louis, Missouri .
Studies of SLE virus evolution indicate that the virus was introduced into North America from tropical America in the late 19th Century . There is evidence that West Nile virus, which was introduced into the United States in 1999, has displaced SLE by more efficient transmission and cross-protective immunity in wild birds . The annual incidence of SLE and the occurrence of epidemics have substantially declined as West Nile virus has spread throughout North America. In contrast, there are increasing reports of SLE infections in tropical America.
St. Louis encephalitis (SLE) virus is a member of the family Flaviviridae, a group of small (40 to 60 nm), enveloped, positive-sense, single-stranded RNA viruses that replicate in the cytoplasm of infected cells. Other members of this virus family include West Nile virus, Japanese encephalitis virus, Murray Valley encephalitis virus, yellow fever virus, and dengue virus. St. Louis encephalitis virus grows in a wide variety of avian and mammalian cell cultures and causes lethal encephalitis in infant mice or hamsters after intracerebral inoculation. SLE virus is antigenically closely related to Japanese encephalitis and West Nile virus, which cause a similar disease (see "Arthropod-borne encephalitides"). This may result in diagnostic confusion, particularly if non-specific serological tests are used. (See 'Diagnosis' below.)
SLE virus strains from the eastern and western United States and from tropical America are distinguishable at the nucleotide sequence level into at least eight lineages and multiple clades [2,4-6], which differ with respect to the mosquito vectors responsible for transmission and the virulence for animal models . The SLE virus Lineage II, which is present east of the Mississippi river, has been associated with severe epidemics, has the highest virulence for laboratory animals, and has the highest case-fatality rate for humans. Although there is evidence for geographic separation and local persistence of strains (eg, Lineage I in California), analyses of SLE virus evolution suggest flow of neotropical strains, particularly from northern Central America, Mexico, and the Caribbean, into the United States by the agency of migratory birds [5,8]. As an example, one analysis identified circulation of an ancestral genotype of SLE circulating in Culex nigripalpus in southern Mexico, which may have given rise to cosmopolitan virus genotypes .
After inoculation of St. Louis encephalitis (SLE) virus into the human host via mosquito saliva, viral replication is initiated in local tissues and regional lymph nodes. Subsequent spread occurs initially to extraneural tissues via the lymphatics and blood. SLE virus replicates in a wide array of cell types, including connective tissue, skeletal muscle, exo- and endocrine glands, and reticuloendothelial tissues. Viremia is terminated approximately one week after infection by neutralizing antibodies and cytotoxic T cells.
- Reisen WK. Epidemiology of St. Louis encephalitis virus. Adv Virus Res 2003; 61:139.
- Baillie GJ, Kolokotronis SO, Waltari E, et al. Phylogenetic and evolutionary analyses of St. Louis encephalitis virus genomes. Mol Phylogenet Evol 2008; 47:717.
- Reisen WK, Lothrop HD, Wheeler SS, et al. Persistent West Nile virus transmission and the apparent displacement St. Louis encephalitis virus in southeastern California, 2003-2006. J Med Entomol 2008; 45:494.
- Kramer LD, Chandler LJ. Phylogenetic analysis of the envelope gene of St. Louis encephalitis virus. Arch Virol 2001; 146:2341.
- Auguste AJ, Pybus OG, Carrington CV. Evolution and dispersal of St. Louis encephalitis virus in the Americas. Infect Genet Evol 2009; 9:709.
- Rodrigues SG, Nunes MR, Casseb SM, et al. Molecular epidemiology of Saint Louis encephalitis virus in the Brazilian Amazon: genetic divergence and dispersal. J Gen Virol 2010; 91:2420.
- Trent DW, Monath TP, Bowen GS, et al. Variation among strains of St. Louis encephalitis virus: basis for a genetic, pathogenetic, and epidemiologic classification. Ann N Y Acad Sci 1980; 354:219.
- Kopp A, Gillespie TR, Hobelsberger D, et al. Provenance and geographic spread of St. Louis encephalitis virus. MBio 2013; 4:e00322.
- Monath TP, Cropp CB, Harrison AK. Mode of entry of a neurotropic arbovirus into the central nervous system. Reinvestigation of an old controversy. Lab Invest 1983; 48:399.
- Samuel MA, Wang H, Siddharthan V, et al. Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis. Proc Natl Acad Sci U S A 2007; 104:17140.
- Gardner JJ, Reyes MG. Pathology. In: St. Louis Encephalitis, Monath TP (Ed), American Public Health Association, Washington, DC 1980. p.551.
- Wang T, Town T, Alexopoulou L, et al. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 2004; 10:1366.
- Samuel MA, Morrey JD, Diamond MS. Caspase 3-dependent cell death of neurons contributes to the pathogenesis of West Nile virus encephalitis. J Virol 2007; 81:2614.
- Moskowitz DW, Johnson FE. The central role of angiotensin I-converting enzyme in vertebrate pathophysiology. Curr Top Med Chem 2004; 4:1433.
- Lim JK, Louie CY, Glaser C, et al. Genetic deficiency of chemokine receptor CCR5 is a strong risk factor for symptomatic West Nile virus infection: a meta-analysis of 4 cohorts in the US epidemic. J Infect Dis 2008; 197:262.
- Pulendran B, Miller J, Querec TD, et al. Case of yellow fever vaccine--associated viscerotropic disease with prolonged viremia, robust adaptive immune responses, and polymorphisms in CCR5 and RANTES genes. J Infect Dis 2008; 198:500.
- McCandless EE, Zhang B, Diamond MS, Klein RS. CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from West Nile virus encephalitis. Proc Natl Acad Sci U S A 2008; 105:11270.
- Diamond MS, Gale M Jr. Cell-intrinsic innate immune control of West Nile virus infection. Trends Immunol 2012; 33:522.
- Viloria GA, Kundro MA, Toibaro JJ, et al. Two cases of Saint Louis encephalitis in HIV-1 infected patients in Buenos Aires. Braz J Infect Dis 2011; 15:607.
- Shrestha B, Ng T, Chu HJ, et al. The relative contribution of antibody and CD8+ T cells to vaccine immunity against West Nile encephalitis virus. Vaccine 2008; 26:2020.
- Siirin MT, Duan T, Lei H, et al. Chronic St. Louis encephalitis virus infection in the golden hamster (Mesocricetus auratus). Am J Trop Med Hyg 2007; 76:299.
- Suzuki M, Phillips CA. St. Louis encephalitis. A histopathologic study of the fatal cases from the Houston epidemic in 1964. Arch Pathol 1966; 81:47.
- Sejvar JJ, Bode AV, Curiel M, Marfin AA. Post-infectious encephalomyelitis associated with St. Louis encephalitis virus infection. Neurology 2004; 63:1719.
- Reisen WK, Fang Y, Martinez VM. Avian host and mosquito (Diptera: Culicidae) vector competence determine the efficiency of West Nile and St. Louis encephalitis virus transmission. J Med Entomol 2005; 42:367.
- Monath TP. Epidemiology. In: St. Louis Encephalitis, Monath TP (Ed), American Public Health Association, Washington, DC 1980. p.239.
- Monath TP, Tsai TF. St. Louis encephalitis: lessons from the last decade. Am J Trop Med Hyg 1987; 37:40S.
- Centers for Disease Control and Prevention (CDC). West Nile virus disease and other arboviral diseases--United States, 2010. MMWR Morb Mortal Wkly Rep 2011; 60:1009.
- Centers for Disease Control and Prevention (CDC). West nile virus disease and other arboviral diseases - United States, 2011. MMWR Morb Mortal Wkly Rep 2012; 61:510.
- Centers for Disease Control and Prevention (CDC). West Nile virus and other arboviral diseases--United States, 2012. MMWR Morb Mortal Wkly Rep 2013; 62:513.
- Spinsanti LI, Díaz LA, Glatstein N, et al. Human outbreak of St. Louis encephalitis detected in Argentina, 2005. J Clin Virol 2008; 42:27.
- Seijo A, Morales A, Poustis G, et al. [Outbreak of St. Louis encephalitis in the Metropolitan Buenos Aires Area]. Medicina (B Aires) 2011; 71:211.
- Mondini A, Cardeal IL, Lázaro E, et al. Saint Louis encephalitis virus, Brazil. Emerg Infect Dis 2007; 13:176.
- Shaman J, Day JF, Stieglitz M. The spatial-temporal distribution of drought, wetting, and human cases of St. Louis encephalitis in southcentral Florida. Am J Trop Med Hyg 2004; 71:251.
- Luby JP, Murphy FK, Gilliam JN, et al. Antigenuria in St. Louis encephalitis. Am J Trop Med Hyg 1980; 29:265.
- Wootton SH, Kaplan SL, Perrotta DM, et al. St. Louis encephalitis in early infancy. Pediatr Infect Dis J 2004; 23:951.
- Brinker KR, Monath TP. The acute disease. In: St. Louis Encephalitis, Monath TP (Ed), American Public Health Association, Washington, DC 1980. p.503.
- Brinker KR, Paulson G, Monath TP, et al. St Louis encephalitis in Ohio, September 1975: clinical and EEG studies in 16 cases. Arch Intern Med 1979; 139:561.
- Okhuysen PC, Crane JK, Pappas J. St. Louis encephalitis in patients with human immunodeficiency virus infection. Clin Infect Dis 1993; 17:140.
- Powell KE, Blakey DL. St. Louis encephalitis: clinical and epidemiologic aspects, Mississippi, 1974. South Med J 1976; 69:1121.
- Finley KH, Riggs N. Convalescence and sequelae. In: St. Louis Encephalitis, Monath TP (Ed), American Public Health Association, Washington, DC 1980. p.535.
- Martin DA, Noga A, Kosoy O, et al. Evaluation of a diagnostic algorithm using immunoglobulin M enzyme-linked immunosorbent assay to differentiate human West Nile Virus and St. Louis Encephalitis virus infections during the 2002 West Nile Virus epidemic in the United States. Clin Diagn Lab Immunol 2004; 11:1130.
- Ledermann JP, Lorono-Pino MA, Ellis C, et al. Evaluation of widely used diagnostic tests to detect West Nile virus infections in horses previously infected with St. Louis encephalitis virus or dengue virus type 2. Clin Vaccine Immunol 2011; 18:580.
- Johnson AJ, Noga AJ, Kosoy O, et al. Duplex microsphere-based immunoassay for detection of anti-West Nile virus and anti-St. Louis encephalitis virus immunoglobulin m antibodies. Clin Diagn Lab Immunol 2005; 12:566.
- Roberson JA, Crill WD, Chang GJ. Differentiation of West Nile and St. Louis encephalitis virus infections by use of noninfectious virus-like particles with reduced cross-reactivity. J Clin Microbiol 2007; 45:3167.
- Pugachev KV, Guirakhoo F, Mitchell F, et al. Construction of yellow fever/St. Louis encephalitis chimeric virus and the use of chimeras as a diagnostic tool. Am J Trop Med Hyg 2004; 71:639.
- Brooks TJ, Phillpotts RJ. Interferon-alpha protects mice against lethal infection with St Louis encephalitis virus delivered by the aerosol and subcutaneous routes. Antiviral Res 1999; 41:57.
- Rahal JJ, Anderson J, Rosenberg C, et al. Effect of interferon-alpha2b therapy on St. Louis viral meningoencephalitis: clinical and laboratory results of a pilot study. J Infect Dis 2004; 190:1084.
- Makhoul B, Braun E, Herskovitz M, et al. Hyperimmune gammaglobulin for the treatment of West Nile virus encephalitis. Isr Med Assoc J 2009; 11:151.
- Stein DA, Shi PY. Nucleic acid-based inhibition of flavivirus infections. Front Biosci 2008; 13:1385.
- Hadler JL, Patel D, Nasci RS, et al. Assessment of Arbovirus Surveillance 13 Years after Introduction of West Nile Virus, United States. Emerg Infect Dis 2015; 21:1159.
- Blaney JE Jr, Speicher J, Hanson CT, et al. Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys. Vaccine 2008; 26:4150.
- Lobigs M, Diamond MS. Feasibility of cross-protective vaccination against flaviviruses of the Japanese encephalitis serocomplex. Expert Rev Vaccines 2012; 11:177.
- TRANSMISSION CYCLE
- CLINICAL FEATURES
- Prodromal symptoms
- Neurologic signs
- Laboratory findings
- Cerebrospinal fluid analysis
- OUTCOME OF INFECTION
- DIFFERENTIAL DIAGNOSIS
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS