Bunyavirus: La Crosse Encephalitis Virus Group #7 Randall Chan Kamal Hamouda

General Overview Of Bunyaviruses Negative-sense RNA virus-Class V Enveloped, spherical 80-100 nm in diameter Genome, composed of 3 RNA segments, Large, Medium and Small (L,M,S respectively) L encodes RNA Dependent RNA-pol M encodes for viral glycoproteins, to attach to host cell S encodes for nucleocapsid protein ssRNA helical structure, L and M are negative sense Ambisense in phlebovirus ]

Mode of Transmission for Bunyavirus Usually found in arthropods or rodents, but some do infect humans, and rarely plants. Generally a vector-borne virus. Transmission occurs via arthropod, with hantavirus through deer mice feces. Closely follows vector activity, such as more in the summer. Has high levels of morbidity and mortality, BSL 4.

Genera of Bunyaviruses Bunyavirus: includes Akabane and California encephalitis Phlebovirus: includes Rift Valley fever virus, Nairovirus: includes Nairobi sheep disease and crimean-congo hemorrhagic fever viruses Uukuvirus: does not contain pathogenic viruses Hantavirus: infects rodents and causes hemorrhagic fever with renal syndrome in humans. Assoc. with fever, lung edema and pulmonary failure Orthobunyaviruses, includes Bunymwera virus

Symptoms of Bunyaviruses Congo-Hemmorhaggic Fever Hantaviruses Dengue

History of La Crosse Virus La Crosse virus was discovered in La Crosse, Wisconsin in 1963. Occurs in the Appalachian/Midwestern regions of the United States. Recent cases have also occurred in the South East of the United States. Suspected to have broader distribution and higher incidence in Eastern United States, but is under-reported.

Mode of Transmission for La Crosse Virus: Mosquito Vector: Virus is maintained during the winter by “transovarial transmission” in mosquito eggs. Zoonotic pathogen: Primarily found in infected treehole mosquito Aedes triseriatus, but can also be found in Aedes canadensis, Aedes sollicitans, and Aedes vexans. The virus is maintained and amplified in treehole mosquito species through transovarial and venereal transmission.

La Crosse Virus Mode of Transmission: Other Mode of Transmission: Amplification can also occur in chipmunks and squirrels by mosquito infection. Humans are dead-end hosts for the virus: Do not circulate enough La Crosse virus in the bloodstream to infect mosquito. The infection cannot be spread from person to person.

La Crosse Virus Transmission Cycle:

Pathogenesis of La Crosse Virus The gut of the vector is infected initially, and after a few days/weeks the virus appears in the saliva. The mosquito is infected, but is not ill. Through mosquito bite, the infected saliva enters the small capillaries or lymphatics of the human or other vertebrate host.

Pathogenesis of La Crosse Virus An incubation period of a few days ensues, after which the vertebrate host enters the bloodstream. The infection is generally inapparent, but in some circumstances can cause host to become febrile. Unless the virus spreads to the target organ, humoral antibody is able to stop the spread of the virus and host recovers. The target organ for La Crosse virus is the brain.

Symptoms & Disease Caused by La Crosse Virus: Takes 5 to 15 days after the bite of an infected mosquito to develop symptoms of La Crosse virus disease. Symptoms for mild cases: Nausea Headache Vomiting Symptoms for severe cases: Seizures Coma Paralysis Permanent brain damage

Symptoms & Disease Caused by La Crosse Virus: La Crosse encephalitis occurs as a nonspecific summertime illness. Severe disease generally occurs in children under the age of 16. Death from La Crosse encephalitis is often rare; occurring in less than 1% of clinical cases.

Group #7-Case Study: A 15 year-old summer camp counselor in Ohio suddenly complained of a headache, nausea, and vomiting; she had a fever and experienced a stiff neck. She was admitted to the hospital, where a spinal tap and examination of cerebrospinal fluid revealed inflammatory cells. She became lethargic over the next day but became alert again after 4 to 5 days.

Case Study Questions: The physician suspected La Crosse encephalitis virus as the agent. What clues pointed to La Crosse virus? What other agents would also be considered in the differential diagnosis? How was the patient infected? How would the transmission of this agent be prevented? How could the local Public Health Department determine the prevalence of La Crosse virus in the environment of the summer camp? What samples would they obtain, and how would they test them?

Patient fits the category 1. The physician suspected La Crosse encephalitis virus as the agent. What clues pointed to La Crosse virus? Symptoms Headaches, vomiting, fever, neck stiffness Inflammatory cells in CSF -General Encephalitis 4-5 days of incubation Location Forested Area in the summertime Patient fits the category Usually found in younger cohorts

Other bunyaviruses are fairly rare in the United States 2. What other agents would also be considered in the differential diagnosis? Meningitis distinguishes it from other viral, fungal or bacterial agents Cannot be distinguished from other tick-borne encephalitis Other bunyaviruses are fairly rare in the United States Others could include Dengue, Eastern Equine Encephalitis Midwestern United States Most likely La Crosse Virus

3. How was the patient infected? Patient was infected through the bite of the vector, mosquito Maintained in nature through vertical transmission in trans-ovarial transmission Can be horizontally transmitted to other vertebrates who act as amplifiers Humans are considered dead-end hosts Mosquito most likely belongs to Aedes triseriatus

4. How would the transmission of this agent be prevented? No vaccination or preventative medication discovered for La Crosse virus infection. Supportive therapy: includes hospitalization, respiratory support, IV fluids, and prevention from other infections. Preventative measures: greatly reduces infection of La Crosse virus.

Preventative Measures: Insect repellent: applying Deet, picaridin, IR3535 or oil of lemon eucalyptus (PMD) on exposed skin or clothing. Clothing: wearing long sleeves, thick pants, and socks will also reduce the chances of a mosquito bite. Can be problematic because of infecting cycle of La Crosse virus occurs during spring/summer.

Preventative Measures: Eliminating mosquito breeding site: Aedes triseriatus are tree hole breeding mosquitoes that live in woodland habitat. Prevent these mosquitoes breeding site by emptying water from containers, barrels, flower pots, etc… Mosquito breeding sites are generally tree holes, filling the tree holes around the environment of breeding sites with soil.

5. How could the local Public Health Department determine the prevalence of La Crosse virus in the environment of the summer camp? What samples would they obtain, and how would they test them?

Prevalence of La Crosse Virus: Collect samples of possible carriers or hosts (mosquitoes, chipmunks/tree squirrels, humans) of the La Crosse virus in the summer camp environment. Samples should be obtained as either CSF (cerebral spinal fluid) or serum.

Prevalence of La Crosse Virus: Reverse transcriptase polymerase chain reaction (RT-PCR): Can be used if virus is isolated. Serological Tests Includes: Complement fixation test Immunofluorescent antibody tests The enzyme-linked immunosorbent assay (ELISA) Hemagglutination inhibition test Neutralization test

Prevalence of La Crosse Virus: Serological tests allow detection of either virus- specified antibody or antigen to the virus in the samples. Testing for immunoglobulin M antibodies (IgM) and neutralizing antibodies to La Crosse virus and many other viruses with similar classification is necessary in order to find out if La Crosse virus is the causative agent.

Prevalence of La Crosse Virus: Samples that are tested positive for LACV should be sent to the Centers for Disease Control and Prevention (CDC) in order to affirm that the samples contain LACV. The samples should indicate whether there is a high or low prevalence of the surrounding summer camp environment. Local Public Health Department can take the appropriate actions depending on the prevalence of La Crosse virus in that environment.

References Shope RE. Bunyaviruses. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 56. Available from: http://www.ncbi.nlm.nih.gov/books/NBK8004/ La Crosse Encephalitis Virus Disease. Ohio Department of Health Fact Sheet[Internet]. 2012 Jan [cited 2012 Oct 27] Available from: http://www.odh.ohio.gov/pdf/idcm/lac.pdf “La Crosse Encephalitis.”Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 16 Oct. 2009. 27 Oct. 2012. http://www.cdc.gov/lac/gen/qa.html