Viral Encephalitis John Nuara, Salwa Touma, Kelly Wines Microbiology and the Control of Infectious Diseases April 22, 2003

Kelly Introduction Introduction Transmission Transmission Outbreaks Outbreaks Reservoir Reservoir

Introduction to Viral Encephalitis Inflammation of brain tissue caused by a viral infection Inflammation of brain tissue caused by a viral infection Can have acute viral encephalitis or post-infectious encephalomyelitis Can have acute viral encephalitis or post-infectious encephalomyelitis Acute viral encephalitis is caused by direct viral infection of neural cells Acute viral encephalitis is caused by direct viral infection of neural cells Post-infection encephalomyelitis follows infection with various viral agents Post-infection encephalomyelitis follows infection with various viral agents

Primary Cause Arboviruses are the most common causes of viral encephalitis Arboviruses are the most common causes of viral encephalitis Arbovirus stands for arthropod-borne viruses Arbovirus stands for arthropod-borne viruses There are 3 virus families associated with encephalitis There are 3 virus families associated with encephalitis Togaviridae (Alphavirus) – most common Togaviridae (Alphavirus) – most common Flaviviridae (Flavavirus) Flaviviridae (Flavavirus) Bunyaviridae (Bunyavirus) Bunyaviridae (Bunyavirus)

Alphavirus Surface Spike-like structures on virion surface Spikes are used to attach to susceptible animal cells RNA-containing viruses

Transmission of Arbovirus Most encephalitides are transmitted by mosquitoes Most encephalitides are transmitted by mosquitoes Other types are transmitted by ticks

Transmission cont.. Infection occurs when the infected arthropod takes a blood meal Infection occurs when the infected arthropod takes a blood meal Most cases of arboviral encephalitis occur from June – September, when arthropods are most active Most cases of arboviral encephalitis occur from June – September, when arthropods are most active In warmer parts of the country, cases can occur year-round In warmer parts of the country, cases can occur year-round

Other Causes Herpes simplex, type 1 (HSV-1) and type 2 (HSV-2) Herpes simplex, type 1 (HSV-1) and type 2 (HSV-2) Enteroviruses – viruses that typically occur in the GI tract Enteroviruses – viruses that typically occur in the GI tract Coltivirus Coltivirus Measles Measles Mumps Mumps Rabies Rabies Rubella Rubella Lymphatic choriomeningitis virus Lymphatic choriomeningitis virus

Other Cause cont... Cytomegalovirus Cytomegalovirus Epstein-Barr virus (EBV) Epstein-Barr virus (EBV) Human immunodeficiency virus (HIV) Human immunodeficiency virus (HIV) Varicella-zoster virus (VZV) Varicella-zoster virus (VZV) Influenza A and B Influenza A and B *Viruses are not the only cause of encephalitis; bacteria, fungus, parasites, toxins, and allergic reactions can also cause it.

Most Common Types of Arboviral Encephalitis in the US Eastern equine encephalitis Eastern equine encephalitis Western equine encephalitis Western equine encephalitis La Crosse encephalitis La Crosse encephalitis St. Louis encephalitis St. Louis encephalitis West Nile encephalitis West Nile encephalitis

Eastern Equine Encephalitis (EEE) Alphavirus Alphavirus Mosquito-borne Mosquito-borne First identified in the 1930’s First identified in the 1930’s Found Found Eastern Seaboard Eastern Seaboard Gulf Coast Gulf Coast Some inland Midwestern area Some inland Midwestern area Most common during warm months Most common during warm months

Eastern Equine Encephalitis cont confirmed cases in US since confirmed cases in US since 1964 One-third of infected individuals die; many others suffer permanent brain damage One-third of infected individuals die; many others suffer permanent brain damage In addition to humans, EEE virus can also produce severe disease in horses, some birds, and puppies In addition to humans, EEE virus can also produce severe disease in horses, some birds, and puppies

Eastern Equine Outbreaks in US

Western Equine Encephalitis (WEE) Alphavirus Alphavirus Mosquito-borne Mosquito-borne First isolated in 1930’s from the brain of a horse with encephalitis First isolated in 1930’s from the brain of a horse with encephalitis Found mainly in western parts of US Found mainly in western parts of US Most common in June and July Most common in June and July

Western Equine Encephalitis cont confirmed cases in US since confirmed cases in US since 1964 Usually causes a mild infection in people Usually causes a mild infection in people Children <1 yr. often suffer permanent complications Children <1 yr. often suffer permanent complications 3% of infected individuals die 3% of infected individuals die

Western Equine Outbreaks in US

La Crosse encephalitis (LAC) Bunyavirus Bunyavirus Transmitted by the tree-hole mosquito Transmitted by the tree-hole mosquito Principal vertebrate hosts Principal vertebrate hosts Eastern chipmunks Eastern chipmunks Gray Squirrels Gray Squirrels Red Foxes Red Foxes

La Crosse Encephalitis cont.. Discovered in La Crosse, Wisconsin in 1963 Discovered in La Crosse, Wisconsin in 1963 Since then, the virus has been identified in several Midwestern and Mid-Atlantic states Since then, the virus has been identified in several Midwestern and Mid-Atlantic states Approximately 75 new cases of LAC are reported per year Approximately 75 new cases of LAC are reported per year Most cases occur in children <16 yrs. Most cases occur in children <16 yrs. Fatality ratio <1% Fatality ratio <1%

La Crosse Outbreaks in US

St. Louis Encephalitis (SLE) Flavavirus Flavavirus Mosquito-borne Mosquito-borne Discovered in St. Louis, Missouri in 1933 Discovered in St. Louis, Missouri in reported cases 1095 reported cases 201 deaths 201 deaths During the same year, human SLE epidemics also occurred in During the same year, human SLE epidemics also occurred in Kansas City, Missouri Kansas City, Missouri St. Joseph, Missouri St. Joseph, Missouri Louisville, Kentucky Louisville, Kentucky

St. Louis encephalitis cont.. In hindsight, the first known SLE epidemic actually occurred in 1932 in Paris, Illinois In hindsight, the first known SLE epidemic actually occurred in 1932 in Paris, Illinois 38 reported cases 38 reported cases 14 deaths 14 deaths Since 1933, there have been at least 41 outbreaks in US Since 1933, there have been at least 41 outbreaks in US Since 1964, there have been 4, 478 reported human cases; with an average of 128 cases/yr. Since 1964, there have been 4, 478 reported human cases; with an average of 128 cases/yr. Outbreaks occurs intermittently Outbreaks occurs intermittently Up to 3,000 cases during large outbreaks Up to 3,000 cases during large outbreaks 20 in other years 20 in other years

St. Louis Encephalitis cont.. Outbreaks most commonly occur in the late summer or early fall; year-round in milder climate (such a St. Louis) Outbreaks most commonly occur in the late summer or early fall; year-round in milder climate (such a St. Louis) Can occur throughout most of the US Can occur throughout most of the US Less than 1% of SLE viral infections are clinically apparent, and most remain undiagnosed Less than 1% of SLE viral infections are clinically apparent, and most remain undiagnosed Clinical disease most often occurs in children and elderly Clinical disease most often occurs in children and elderly 7% children die 7% children die 30% elderly die 30% elderly die

St. Louis Outbreaks in US

West Nile Virus Flavavirus Flavavirus First isolated in the West Nile Province of Uganda in 1937 First isolated in the West Nile Province of Uganda in 1937 First epidemic occurred in Israel in the 1950s First epidemic occurred in Israel in the 1950s Primarily affects individuals in Africa, the Middle East, western Asia, and Europe Primarily affects individuals in Africa, the Middle East, western Asia, and Europe In late August and September 1999, there was an outbreak in New York City and neighboring counties In late August and September 1999, there was an outbreak in New York City and neighboring counties Outbreak was initially attributed to St. Louis Encephalitis Outbreak was initially attributed to St. Louis Encephalitis Most likely introduced to North America through international travel of infected persons to New York or by imported infected birds Most likely introduced to North America through international travel of infected persons to New York or by imported infected birds

West Nile Virus cont.. The virus can infect people, horses, many birds, and some other animals The virus can infect people, horses, many birds, and some other animals Infection usually occurs in the late summer or early fall Infection usually occurs in the late summer or early fall Most people who become infected with West Nile Virus have either no symptoms or only mild ones. Most people who become infected with West Nile Virus have either no symptoms or only mild ones. A small percentage (<1%) of patients will develop more severe diseases from infection, including West Nile Encephalitis A small percentage (<1%) of patients will develop more severe diseases from infection, including West Nile Encephalitis Infections are most common in children and the elderly and as many as 10% of infected individuals will die Infections are most common in children and the elderly and as many as 10% of infected individuals will die

West Nile Outbreaks in US

Mosquito Breeding Grounds

Discarded Tires

Lakes and Ponds

Trash

Plants are natural incubators

Salwa Structure Structure Pathogenesis Pathogenesis Symptoms Symptoms Diagnosis Diagnosis

John Treatment Treatment Prevention Prevention Genetic Engineering Genetic Engineering Weaponization Weaponization