Jamestown Canyon encephalitis
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Jamestown Canyon encephalitis is an infectious disease caused by the Jamestown Canyon virus, an orthobunyavirus of the California serogroup. It is mainly spread during the summer by different mosquito species in the United States and Canada. The virus is one of a group of mosquito-borne or arthropod-borne viruses, also called arboviruses, that can cause fever and
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
or meningoencephalitis, mostly in adults. Jamestown Canyon virus disease is relatively rare; in the United States, the CDC found only 31 disease cases from 2000 to 2013, but it is likely under-recognized and probably
endemic Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found elsew ...
throughout most of the United States and parts of Canada.


Signs and symptoms

About 2 days to 2 weeks after the bite of an infected mosquito, disease symptoms of a nonspecific summertime illness with sore throat, runny nose and cough, followed by fever,
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
, nausea and vomiting can develop. Many cases are asymptomatic, although the ratio of symptomatic to asymptomatic cases is unknown. Neuroinvasive disease occurs in two thirds of reported cases and is characterized by severe headache and neck stiffness as in
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
or increasing lethargy and
altered mental status An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment. A mildly depressed level of consciousne ...
up to coma as in meningoencephalitis. Roughly half of reported cases are hospitalized, but deaths from the virus are rare. No acquisition from a blood transfusion has been reported.


Virology

The Jamestown Canyon virus is an orthobunyavirus and was first isolated in 1961 from
Culiseta ''Culiseta'' is a genus (biology), genus of mosquitoes. Most ''Culiseta'' species are cold-adapted, and only occur in warmer climates during the colder parts of the year or at higher elevations where temperatures are lower. Species found in South ...
mosquitoes in
Jamestown, Colorado The historic Town of Jamestown is a Statutory Town in Boulder County, Colorado, United States. The population was 274 at the 2010 United States Census. It was named for James Smith, an early discoverer of gold.Aedes,
Coquillettidia perturbans ''Coquillettidia perturbans'' is a species of mosquito that have been documented in every continent except Antarctica. This mosquito is a known as a vector of West Nile virus and Eastern equine encephalomyelitis. The geographic range of ''C.  ...
, Culex,
Culiseta ''Culiseta'' is a genus (biology), genus of mosquitoes. Most ''Culiseta'' species are cold-adapted, and only occur in warmer climates during the colder parts of the year or at higher elevations where temperatures are lower. Species found in South ...
and Ochlerotatus species in northern states of the mainland US, in various mammals throughout mainland North America, and identified in humans throughout the United States.


Lifecycle

The virus is transmitted in saliva to a vertebrate host when an infected mosquito takes a blood meal. It thus cycles between mosquito and vertebrate amplifier hosts, mainly
white-tailed deer The white-tailed deer (''Odocoileus virginianus''), also known as the whitetail or Virginia deer, is a medium-sized deer native to North America, Central America, and South America as far south as Peru and Bolivia. It has also been introduced t ...
. In a study from
Newfoundland Newfoundland and Labrador (; french: Terre-Neuve-et-Labrador; frequently abbreviated as NL) is the easternmost province of Canada, in the country's Atlantic region. The province comprises the island of Newfoundland and the continental region ...
, JCV was significantly associated with large mammals such as sheep, cattle and horses. In Michigan and Ontario moose and bison are believed to be the primary reservoir. The virus winters in mosquito eggs, which it reaches by transovarial transmission. The female mosquito lays eggs that carry the virus, and the offspring can transmit the virus to deer or ruminants and humans. Infected mosquitoes were found equally distributed throughout the state of Connecticut, irrespective of land use.


Molecular biology

The full
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
has been sequenced. The authors found a relatively high level of amino acid sequence conservation from viruses isolated 57 years apart "indicating that the virus is in relative evolutionary stasis". They also found JCV to be genetically similar to Ingå virus in Northern Europe (Finland, Sweden), "suggesting that much of the northern hemisphere contains JCV or similar variants". The negative sense RNA genome is in three segments. The L segment encodes the L endonuclease (an RNA-dependent RNA polymerase enzyme) for genome replication and mRNA synthesis. The M segment encodes a polyprotein, further cleaved in the Gn and Gc surface glycoproteins for attachment and the NSm nonstructural protein that influences virulence. The S segment encodes the NSs protein for immune suppression and virulence, and the N structural nucleocapsid protein.


Diagnosis

The
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
considers a person with JCV infection laboratory-confirmed if: JCV isolated from or JCV-specific antigen or genomic sequences detected in tissue, blood, cerebrospinal fluid, or other body fluids; 2) equal or more than 4-fold change in JCV-specific neutralizing antibody titers between acute and
convalescent Convalescence is the gradual recovery of health and strength after illness or injury. It refers to the later stage of an infectious disease or illness when the patient recovers and returns to previous health, but may continue to be a source of ...
samples; or 3) JCV or LACV
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
antibodies in serum with JCV-specific neutralizing antibodies equal or more than 4-fold higher than LACV-specific neutralizing antibody titers in the same specimen or a later specimen. JCV-antibody testing has only been available at the CDC and the New York State Department of Health. The CDC has used
plaque reduction neutralization test The plaque reduction neutralization test is used to quantify the titer of neutralizing antibody for a virus. The serum sample or solution of antibody to be tested is diluted and mixed with a viral suspension. This is incubated to allow the antibody ...
s to detect JCV neutralizing antibodies since 1995. The test is automatically done on all samples testing positive or equivocal for La Crosse Virus IgM antibodies by
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
. In 2010 CDC developed an ELISA also for JCV IgM . Similarly, the New York State Department of Health has performed JCV plaque reduction neutralization tests since 2000 on samples positive for California serogroup IgG antibodies. It does the latter by an
immunofluorescence assay Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specifi ...
. Prior to the 1990s, the only tests for California serogroup virus infections performed by most state diagnostic laboratories were complement-fixation test and
hemagglutination inhibition The hemagglutination assay or haemagglutination assay (HA) and the hemagglutination inhibition assay (HI or HAI) were developed in 1941–42 by American virologist George Hirst as methods for quantifying the relative concentration of viruses, bact ...
tests with La Crosse virus, but these failed to detect antibody to Jamestown Canyon virus.


Differential diagnosis

Besides La Crosse virus, other arboviruses producing similar disease in a similar geographic location include first and foremost
West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...
,
Powassan virus ''Powassan virus (POWV)'' is a ''Flavivirus'' transmitted by ticks, found in North America and in the Russian Far East. It is named after the town of Powassan, Ontario, where it was identified in a young boy who eventually died from it. It can ca ...
, Eastern equine encephalitis virus, Saint Louis encephalitis and Western equine encephalitis virus, the latter two not being reportable to CDC. For 2013, CDC reported that of 22 JCV disease cases, 15 (68%) were neuroinvasive, which is a slightly higher percentage than for West Nile virus (51%), but less common than for the other arboviruses, with La Crosse virus being 91%, Eastern equine encephalitis virus 100% and Powassan virus 80% neuroinvasive.


Treatment and prevention

No specific therapy exists for arboviral infections; treatment is limited to supportive care and managing complications, such as relieving increased intracranial pressure. Preventing and decreasing the morbidity from JCV disease depends on control of the mosquito vectors and personal protection to reduce mosquito bites. The NIAID reported in 2012, that it had constructed a candidate virus for a live attenuated virus vaccine.


Epidemiology

Since 2004, the disease must be reported to CDC (passive surveillance, ArboNET). JCV has been mostly reported in adults rather than in children ( median age 48 years versus 8 years), and is more likely to cause meningitis than encephalitis compared to illness caused by
La Crosse virus La Crosse encephalitis is an encephalitis caused by an arbovirus (the La Crosse virus) which has a mosquito vector ('' Ochlerotatus triseriatus'' synonym ''Aedes'' ''triseriatus''). La Crosse encephalitis virus (LACV) is one of a group of m ...
. It also occurs throughout the summer (May until September), or even throughout the year rather than mostly in August, which may be due to the diversity of mosquitoes it can infect. ;Increasing awareness and more testing In the latest US review covering 2000–2013, more than half of cases were identified in 2013 alone, the first year the CDC implemented routine JCV IgM antibody testing. ;Geography Historically, most cases of encephalitis reported to the CDC occurred in the north of the mainland United States. JCV disease most likely has a broader distribution, but is unidentified and under-reported, because testing is not considered and not straightforward. In 2013, of 10 states reporting cases, eight states reported their first JCV cases: Georgia, Idaho, Massachusetts, Minnesota, New Hampshire, Oregon, Pennsylvania, and Rhode Island. In August 2015, the Iowa Department of Public Health confirmed one case of JCV. In July 2017, the Maine Center for Disease Control announced what is believed to be Maine's first known case. ;Season Historically disease was reported to occur from late spring through early fall. However, for 2013, dates of illness onset ranged from January through November, with 14 (64%) of the 22 cases occurring during July until September.


References


Further reading

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External links


The Encephalitis Society
A comprehensive resource on Encephalitis and providing support and information to those affected and their families {{DEFAULTSORT:Jamestown Canyon Orthobunyaviruses Viral encephalitis