La Crosse encephalitis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anthony Gallo, B.S. [2]
Synonyms and keywords: LACV; LaCrosse virus;
Overview
Historical Perspective
In 1963, the cause of La Crosse encephalitis was discovered near La Crosse, Wisconsin by the Hooper Foundation.[1] La Crosse encephalitis was first discovered within the brain during the autopsy of a 4 year old boy who died from encephalitis. Upon further microscopic histopathological analysis, it was confirmed that the La Crosse virus was genetically related to the California encephalitis virus.[2]
Classification
There is no classification system established for La Crosse encephalitis. La Crosse encephalitis virus belongs to the Group V negative-sense ssRNA virus within the Bunyaviridae family of viruses, and the genus Orthobunyavirus. La Crosse encephalitis virus is also known as an arbovirus, or an arthropod-borne virus.[3] The La Crosse virus is the principal member of the California encephalitis serogroup, which contains genetically similar viruses such as California encephalitis virus.[4]
Pathophysiology
La Crosse encephalitis virus is usually transmitted via mosquitos to the human host.[3] La Crosse encephalitis virus contains negative-sense viral RNA; this RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation. California encephalitis virus is made up of an enveloped virion with a spherical capsid. The envelope contains G1 glycoproteins. Neutralizing antibodies against these proteins block fusion of the virus with host cells and inhibit hemagglutination. The virus genome is over 12000 nucleotides in length, approximately 90-100 nm in diameter, and consists of three segments of various sized single-stranded RNA (negative sense and ambi-sense).[5]
La Crosse encephalitis virus is contracted by the bite of an infected mosquito, primarily Aedes triseriatus. The virus is maintained and amplified in Aedes triseriatus populations through transovarial and venereal transmission. The virus overwinters in the mosquito egg. Amplification also occurs in chipmunks and squirrels, upon which mosquitos feed. Humans are dead-end hosts for the virus, meaning there is an insufficient amount of California encephalitis virus in the blood stream to infect a mosquito. Subsequently, the disease cannot be spread to other humans. The incubation period is 5-15 days.[4]
La Crosse encephalitis virus is transmitted in the following pattern:[6]
- Virus attaches to host receptors though Gn-Gc glycoprotein dimer, and is endocytosed into vesicles in the host cell
- Fusion of virus membrane with the vesicle membrane; ribonucleocapsid segments are released in the cytoplasm
- Transcription, viral mRNAs are capped in the cytoplasm
- Replication presumably starts when sufficient nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes
- The ribonucleocapsids buds at Golgi apparatus, releasing the virion by exocytosis
Causes
La Crosse encephalitis virus causes La Crosse encephalitis.
Differential Diagnosis
La Crosse encephalitis virus must be differentiated from other diseases that cause fever, headache, seizures, and altered mental status, such as:[3][7][8][9]
| Disease | Findings |
|---|---|
| California encephalitis virus | California encephalitis virus presents with acute inflammation of the brain, caused by a viral infection; complications include severe brain damage. Other findings include nausea, headache, vomiting in milder cases and seizures, coma, paralysis and permanent brain damage in severe cases. |
| Vector-borne encephalitis | Vector-borne encephalitis presents with acute inflammation of the brain, caused by a bacterial infection; complications include severe brain damage as the inflamed brain pushes against the skull, potentially leading to mortality. |
| Viral encephalitis | Viral encephalitis presents with acute inflammation of the brain, caused by a viral infection; complications include severe brain damage as the inflamed brain pushes against the skull, potentially leading to mortality. |
| Encephalopathy | Encephalopathy presents with steady depression, generalized seizures. Generally absent are fever, headache, leukocytosis, and pleocytosis; MRI often appears normal. |
| Meningitis | Meningitis presents with headache, altered mental status, and inflammation of the meninges, which may develop in the setting of an infection, physical injury, cancer, or certain drugs; it may have an indolent evolution, resolving on its own, or may present as an rapidly evolving inflammation, causing neurologic damage and possible mortality. |
| Brain abscess | Brain abscess presents with an abscess in the brain caused by the inflammation and accumulation of infected material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head trauma or neurological procedures. |
| Acute disseminated encephalomyelitis (ADEM) | Acute disseminated encephalomyelitis presents with scattered foci of demyelination and perivenular inflammation; it can cause focal neurological signs and decreased ability to focus. |
Epidemiology and Demographics
Incidence
There are approximately 80-100 cases of La Crosse encephalitis per year in the United States. There is significant under-diagnosis and under-reporting of less severe cases of La Crosse encephalitis.[5]
Age
La Crosse encephalitis virus commonly affects individuals between 6 months old and 15 years of age.[10] Adults comprise the most under-diagnosed group.
Seasonal
The majority of La Crosse encephalitis virus cases are reported between in the summer months between July and September, and peaks in August.[10]
Geographic Location
The majority of California encephalitis virus cases are reported in the Midwestern United States, especially those living in rural and suburban settings surrounded by deciduous forests.[10] Historically, most cases of La Crosse encephalitis occur in the Midwest states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases are being reported from states in the Southeast United States (Virginia, Virginia, North Carolina, Alabama and Mississippi).
Maps regarding geographic distribution of La Crosse encephalitis cases can be found here.
Risk Factors
Common risk factors in the development of La Crosse encephalitis virus include:
- Young age
- Immunosuppression
- Residing or working in rural and suburban settings
- Mosquito contact
- Summer season
- Outdoor activities such as camping or hunting
Natural History, Complications, and Prognosis
Screening
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
CT
MRI
Treatment
Medical Therapy
Surgery
Prevention
References
- ↑ Tselis AC, Booss J. Neurovirology, Handbook of Clinical Neurology Series (Series Editors: Aminoff, Boller, Swaab). Newnes; 2014.
- ↑ THOMPSON WH, KALFAYAN B, ANSLOW RO (1965). "ISOLATION OF CALIFORNIA ENCEPHALITIS GROUP VIRUS FROM A FATAL HUMAN ILLNESS". Am J Epidemiol. 81: 245–53. PMID 14261030.
- ↑ 3.0 3.1 3.2 M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.
- ↑ 4.0 4.1 La Crosse Encephalitis. Ohio Department of Health. http://www.odh.ohio.gov/pdf/idcm/lac.pdf Accessed on March 1, 2016.
- ↑ 5.0 5.1 La Crosse Encephalitis. Centers for Disease Control and Prevention (2009). http://www.cdc.gov/lac/ Accessed on March 1, 2016.
- ↑ Bunyaviridae. SIB Swiss Institute of Bioinformatics http://viralzone.expasy.org/viralzone/all_by_species/82.html Accessed on March 1, 2016
- ↑ Kennedy PG (2004). "Viral encephalitis: causes, differential diagnosis, and management". J Neurol Neurosurg Psychiatry. 75 Suppl 1: i10–5. PMC 1765650. PMID 14978145.
- ↑ Arboviral Infections (arthropod-borne encephalitis, eastern equine encephalitis, St. Louis encephalitis, California encephalitis, Powassan encephalitis, West Nile encephalitis). New York State Department of Health (2006). https://www.health.ny.gov/diseases/communicable/arboviral/fact_sheet.htm Accessed on February 23, 2016
- ↑ La Crosse encephalitis fact sheet (2013). http://www.health.state.mn.us/divs/idepc/diseases/lacencephalitis/lc.html Accessed on March 1, 2016.
- ↑ 10.0 10.1 10.2 Goldman L, Schafer AI. Goldman's Cecil Medicine. Elsevier Health Sciences; 2011.
Historically, most cases of LAC encephalitis occur in the upper Midwestern states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases are being reported from states in the mid-Atlantic (West Virginia, Virginia and North Carolina) and southeastern (Alabama and Mississippi) regions of the country. It has long been suspected that LAC encephalitis has a broader distribution and a higher incidence in the eastern United States, but is under-reported because the etiologic agent is often not specifically identified.
Other similar diseases that are spread by mosquitoes include: Western and Eastern Equine Encephalitis, Japanese Encephalitis, St. Louis Encephalitis and West Nile Virus.
Symptoms
Symptoms include nausea, headache, vomiting in milder cases and seizures, coma, paralysis and permanent brain damage in severe cases.
LAC encephalitis initially presents as a nonspecific summertime illness with fever, headache, nausea, vomiting and lethargy. Severe disease occurs most commonly in children under the age of 16 and is characterized by seizures, coma, paralysis, and a variety of neurological sequelae after recovery. Death from LAC encephalitis occurs in less than 1% of clinical cases. In many clinical settings, pediatric cases presenting with CNS involvement are routinely screened for herpes or enteroviral etiologies. Since there is no specific treatment for LAC encephalitis, physicians often do not request the tests required to specifically identify LAC virus, and the cases are reported as aseptic meningitis or viral encephalitis of unknown etiology.
Like with many infections, the very young, the very old and the immunocompromised are at a higher risk of developing severe symptoms.
Treatment
No specific therapy is available at present for La Crosse encephalitis, and management is limited to alleviating the symptoms and balancing fluids and electrolyte levels.
Gallery
-
![This electron micrograph reveals the morphologic traits of the La Cross virus (LCV), a Bunyaviridae virus family member. From Public Health Image Library (PHIL). [1]](/images/7/75/Bunyaviridae08.jpeg)
This electron micrograph reveals the morphologic traits of the La Cross virus (LCV), a Bunyaviridae virus family member. From Public Health Image Library (PHIL). [1]
-
![This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse (LAC) encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL). [1]](/images/e/ed/Bunyaviridae07.jpeg)
This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse (LAC) encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL). [1]
-
![This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse (LAC) encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL). [1]](/images/f/fd/Bunyaviridae05.jpeg)
This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse (LAC) encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL). [1]
-
![This 1975 transmission electron micrograph (TEM) revealed the presence of a number of Bunyamwera virus virions, a member of the virus family Bunyaviridae, and the genus Bunyavirus. From Public Health Image Library (PHIL). [1]](/images/3/3f/Bunyaviridae04.jpeg)
This 1975 transmission electron micrograph (TEM) revealed the presence of a number of Bunyamwera virus virions, a member of the virus family Bunyaviridae, and the genus Bunyavirus. From Public Health Image Library (PHIL). [1]
-
![This transmission electron micrograph (TEM) revealed the presence of numerous Ganjam virus virions in this tissue specimen. This Bunyaviridae family member is antigenically, closely related to, and an Asian variant of, the Nairobi sheep disease virus (NSDV). From Public Health Image Library (PHIL). [1]](/images/0/00/Bunyaviridae03.jpeg)
This transmission electron micrograph (TEM) revealed the presence of numerous Ganjam virus virions in this tissue specimen. This Bunyaviridae family member is antigenically, closely related to, and an Asian variant of, the Nairobi sheep disease virus (NSDV). From Public Health Image Library (PHIL). [1]
-
![This image reveals some of the cytoarchitectural features seen in a lymph node specimen that had been extracted from a patient suspected of a Hantavirus illness. Note the concentration of lymphohistiocytic infiltrates, almost all cases have expanded paracortical regions, or T-cell regions with immunoblasts, which sometimes extend into the cortex and into the medulla. From Public Health Image Library (PHIL). [1]](/images/2/2c/Bunyaviridae01.jpeg)
This image reveals some of the cytoarchitectural features seen in a lymph node specimen that had been extracted from a patient suspected of a Hantavirus illness. Note the concentration of lymphohistiocytic infiltrates, almost all cases have expanded paracortical regions, or T-cell regions with immunoblasts, which sometimes extend into the cortex and into the medulla. From Public Health Image Library (PHIL). [1]
![This electron micrograph reveals the morphologic traits of the La Cross virus (LCV), a Bunyaviridae virus family member. From Public Health Image Library (PHIL). [1]](/index.php/File:Bunyaviridae08.jpeg)
![This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse (LAC) encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL). [1]](/index.php/File:Bunyaviridae07.jpeg)
![This negatively-stained transmission electron micrograph (TEM) revealed the presence of La Crosse (LAC) encephalitis virus ribonucleoprotein particles (RNP). From Public Health Image Library (PHIL). [1]](/index.php/File:Bunyaviridae05.jpeg)
![This 1975 transmission electron micrograph (TEM) revealed the presence of a number of Bunyamwera virus virions, a member of the virus family Bunyaviridae, and the genus Bunyavirus. From Public Health Image Library (PHIL). [1]](/index.php/File:Bunyaviridae04.jpeg)
![This transmission electron micrograph (TEM) revealed the presence of numerous Ganjam virus virions in this tissue specimen. This Bunyaviridae family member is antigenically, closely related to, and an Asian variant of, the Nairobi sheep disease virus (NSDV). From Public Health Image Library (PHIL). [1]](/index.php/File:Bunyaviridae03.jpeg)
![This image reveals some of the cytoarchitectural features seen in a lymph node specimen that had been extracted from a patient suspected of a Hantavirus illness. Note the concentration of lymphohistiocytic infiltrates, almost all cases have expanded paracortical regions, or T-cell regions with immunoblasts, which sometimes extend into the cortex and into the medulla. From Public Health Image Library (PHIL). [1]](/index.php/File:Bunyaviridae01.jpeg)