i.e. arboviruses, are viruses that are maintained in nature through
biological transmission between susceptible vertebrate hosts by blood feeding
arthropods (mosquitoes, psychodids, ceratopogonids, and ticks). Vertebrate
infection occurs when the infected arthropod takes a blood meal. The term
'arbovirus' has no taxonomic significance. Arboviruses that cause human
encephalitis are members of three virus families: the Togaviridae
(genus Alphavirus), Flaviviridae, and
All arboviral encephalitides are zoonotic, being maintained in
complex life cycles involving a nonhuman primary
vertebrate host and a primary arthropod vector. These cycles usually remain
undetected until humans encroach on a natural focus, or the virus escapes this
focus via a secondary vector or vertebrate host as the result of some ecologic
change. Humans and domestic animals can develop clinical illness but usually
are "dead-end" hosts because they do not produce significant viremia,
and do not contribute to the transmission cycle. Many arboviruses that cause
encephalitis have a variety of different vertebrate hosts and some are
transmitted by more than one vector. Maintenance of the viruses in nature may
be facilitated by vertical transmission (e.g., the virus is transmitted from
the female through the eggs to the offspring).
Arboviral encephalitides have a global
distribution, but there are four main virus agents of encephalitis in the
United States: eastern equine encephalitis (EEE), western equine encephalitis
(WEE), St. Louis encephalitis (SLE) and LaCrosse (LAC) encephalitis, all of
which are transmitted by mosquitoes. Another virus, Powassan, is a minor cause
of encephalitis in the northern United States, and is transmitted by ticks. A
new Powassan-like virus has recently been isolated from deer ticks. Its
relatedness to Powassan virus and its ability to cause disease has not been
well documented. Most cases of arboviral encephalitis occur from June through
September, when arthropods are most active. In milder (i.e., warmer) parts of
the country, where arthropods are active late into the year, cases can occur
into the winter months.
The majority of human infections are asymptomatic or may result in a
nonspecific flu-like syndrome. Onset may be insidious or sudden with fever,
headache, myalgias, malaise and occasionally prostration. Infection may,
however, lead to encephalitis, with a fatal outcome or permanent neurologic
sequelae. Fortunately, only a small proportion of infected persons progress to
Experimental studies have shown that invasion of the central nervous system
(CNS), generally follows initial virus replication in various peripheral sites
and a period of viremia. Viral transfer from the blood to the CNS through the
olfactory tract has been suggested. Because the arboviral encephalitides are
viral diseases, antibiotics are not effective for treatment and no effective
antiviral drugs have yet been discovered. Treatment is supportive, attempting
to deal with problems such as swelling of the brain, loss of the automatic
breathing activity of the brain and other treatable complications like
There are no commercially available human vaccines for these U.S. diseases.
There is a Japanese encephalitis vaccine available in the U.S. A tick-borne
encephalitis vaccine is available in Europe. An equine vaccine is available for
EEE, WEE and Venezuelan equine encephalitis (VEE). Arboviral encephalitis can
be prevented in two major ways: personal protective measures and public health
measures to reduce the population of infected mosquitoes. Personal measures
include reducing time outdoors particularly in early evening hours, wearing
long pants and long sleeved shirts and applying mosquito repellent to exposed
skin areas. Public health measures often require spraying of insecticides to
kill juvenile (larvae) and adult mosquitoes.
Selection of mosquito control methods depends on what needs to be achieved;
but, in most emergency situations, the preferred method to achieve maximum
results over a wide area is aerial spraying. In many states aerial spraying may
be available in certain locations as a means to control nuisance mosquitoes.
Such resources can be redirected to areas of virus activity. When aerial
spraying is not routinely used, such services are usually contracted for a
given time period.
Financing of aerial spraying costs during large outbreaks is usually
provided by state emergency contingency funds. Federal funding of emergency
spraying is rare and almost always requires a federal disaster declaration.
Such disaster declarations usually occur when the vector-borne disease has the
potential to infect large numbers of people, when a large population is at risk
and when the area requiring treatment is extensive. Special large planes
maintained by the United States Air Force can be called upon to deliver the
insecticide(s) chosen for such emergencies.
Laboratory diagnosis of human arboviral encephalitis has changed greatly
over the last few years. In the past, identification of antibody relied on four
tests: hemagglutination-inhibition, complement fixation, plaque reduction
neutralization test, and the indirect fluorescent antibody (IFA) test. Positive
identification using these immunoglobulin M (IgM) - and IgG-based assays
requires a four-fold increase in titer between acute and convalescent serum
samples. With the advent of solid-phase antibody-binding assays, such as
enzyme-linked immunosorbent assay (ELISA), the diagnostic algorithm for
identification of viral activity has changed. Rapid serologic assays such as
IgM-capture ELISA (MAC-ELISA) and IgG ELISA may now be employed soon after
infection. Early in infection, IgM antibody is more specific, while later in
infection, IgG antibody is more reactive. Inclusion of monoclonal antibodies
(MAbs) with defined virus specificities in these solid phase assays has allowed
for a level of standardization that was not previously possible.
Virus isolation and identification have also been useful in defining viral
agents in serum, cerebrospinal fluid and mosquito vectors. While virus
isolation still depends upon growth of an unknown virus in cell culture or
neonatal mice, virus identification has also been greatly facilitated by the
availability of virus-specific MAbs for use in IFA assays. Similarly, MAbs with
avidities sufficiently high to allow for specific binding to virus antigens in
a complex protein mixture (e.g., mosquito pool suspensions) have enhanced our
ability to rapidly identify virus agents in situ. While polymerase
chain reaction (PCR) has been developed to identify a number of viral agents,
such tests have not yet been validated for routine rapid identification in the
Mosquito-borne encephalitis offers a rare opportunity in public health to
detect the risk of a disease before it occurs and to intervene to reduce that
risk substantially. The surveillance required to detect risk is being
increasingly refined by the potential utilization of these new technologies
which allows for rapid identification of dangerous viruses in mosquito
populations. These rapid diagnostic techniques used in threat recognition can
shorten public health response time and reduce the geographic spread of
infected vectors and thereby the cost of containing them.
LaCrosse (LAC) encephalitis was discovered in LaCrosse, Wisconsin in 1963.
Since then, the virus has been identified in several Midwestern and
Mid-Atlantic states. During an average year, about 75 cases of LAC encephalitis
are reported to the CDC. Most cases of LAC encephalitis occur in children under
16 years of age. LAC virus is a Bunyavirus and is a zoonotic pathogen cycled
between the daytime-biting treehole mosquito, Aedes triseriatus, and
vertebrate amplifier hosts (chipmunks, tree squirrels) in deciduous forest
habitats. The virus is maintained over the winter by transovarial transmission
in mosquito eggs. If the female mosquito is infected, she may lay eggs that
carry the virus, and the adults coming from those eggs may be able to transmit
the virus to chipmunks and to humans.
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
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.
Also found in the United States, Jamestown Canyon and Cache Valley viruses
are related to LAC, but rarely cause encephalitis.
Eastern Equine Encephalitis
Eastern equine encephalitis (EEE) is also caused by a virus transmitted to
humans and equines by the bite of an infected mosquito. EEE virus is an
alphavirus that was first identified in the 1930's
and currently occurs in focal locations along the eastern seaboard, the Gulf
Coast and some inland Midwestern locations of the United States. While small
outbreaks of human disease have occurred in the United States, equine
epizootics can be a common occurrence during the summer and fall.
It takes from 4-10 days after the bite of an infected mosquito for an
individual to develop symptoms of EEE. These symptoms begin with a sudden onset
of fever, general muscle pains, and a headache of increasing severity. Many
individuals will progress to more severe symptoms such as seizures and coma.
Approximately one-third of all people with clinical encephalitis caused by EEE
will die from the disease and of those who recover, many will suffer permanent
brain damage with many of those requiring permanent institutional care.
In addition to humans, EEE virus can produce severe disease in: horses,
some birds such as pheasants, quail, ostriches and emus, and even puppies.
Because horses are outdoors and attract hordes of biting mosquitoes, they are
at high risk of contracting EEE when the virus is present in mosquitoes. Human
cases are usually preceded by those in horses and exceeded in numbers by horse
cases which may be used as a surveillance tool.
EEE virus occurs in natural cycles involving birds and Culiseta
melanura, in some swampy areas nearly every year during the warm months.
Where the virus resides or how it survives in the winter is unknown. It may be
introduced by migratory birds in the spring or it may remain dormant in some
yet undiscovered part of its life cycle. With the onset of spring, the virus
reappears in the birds (native bird species do not seem to be affected by the
virus) and mosquitoes of the swamp. In this usual cycle of transmission, virus
does not escape from these areas because the mosquito involved prefers to feed
upon birds and does not usually bite humans or other mammals.
For reasons not fully understood, the virus may escape from enzootic foci
in swamp areas in birds or bridge vectors such as Coquilletidia
perturbans and Aedes sollicitans. These species feed on both
birds and mammals and can transmit the virus to humans, horses, and other
hosts. Other mosquito species such as Ae. vexans and Culex
nigripalpus can also transmit EEE virus. When health officials
maintain surveillance for EEE virus activity, this movement out of the swamp
can be detected, and if the level of activity is sufficiently high, can
recommend and undertake measures to reduce the risk to humans.
Western Equine Encephalitis
The alphavirus western equine encephalitis (WEE) was first isolated in
California in 1930 from the brain of a horse with encephalitis, and remains an
important cause of encephalitis in horses and humans in North America, mainly
in western parts of the USA and Canada. In the western United States, the
enzootic cycle of WEE involves passerine birds, in which the infection is
inapparent, and culicine mosquitoes, principally Cx. tarsalis, a
species that is associated with irrigated agriculture and stream drainages. The
virus has also been isolated from a variety of mammal species. Other important
mosquito vector species include Aedes melanimon in California, Ae.
dorsalis in Utah and New Mexico and Ae. campestris in New Mexico.
WEE virus was isolated from field collected larvae of Ae. dorsalis,
providing evidence that vertical transmission may play an important role in the
maintenance cycle of an alphavirus.
Expansion of irrigated agriculture in the North Platte River Valley during
the past several decades has created habitats and conditions favorable for
increases in populations of granivorous birds such as the house sparrow,
Passer domesticus, and mosquitoes such as Cx. tarsalis,
Aedes dorsalis and Aedes melanimon. All of these species may
play a role in WEE virus transmission in irrigated areas. In addition to
Cx. tarsalis, Ae. dorsalis and Ae. melanimon, WEE virus also has been
isolated occasionally from some other mosquito species present in the
area. Two confirmed and several suspect cases of WEE were reported from Wyoming
in 1994. In 1995, two strains of WEE virus were isolated from Culex
tarsalis and neutralizing antibody to WEE virus was demonstrated in sera
from pheasants and house sparrows. During 1997, 35 strains of WEE virus were
isolated from mosquitoes collected in Scotts Bluff County, Nebraska.
Human WEE cases are usually first seen in June or July. Most WEE infections
are asymptomatic or present as mild, nonspecific illness. Patients with
clinically apparent illness usually have a sudden onset with fever, headache,
nausea, vomiting, anorexia and malaise, followed by altered mental status,
weakness and signs of meningeal irritation. Children, especially those under 1
year old, are affected more severely than adults and may be left with permanent
sequelae, which is seen in 5 to 30% of young patients. The mortality rate is
St. Louis encephalitis
In the United States, the leading cause of epidemic flaviviral encephalitis
is St. Louis encephalitis (SLE) virus. SLE is the most common
mosquito-transmitted human pathogen in the U.S. While periodic SLE epidemics
have occurred only in the Midwest and southeast, SLE virus is distributed
throughout the lower 48 states. Since 1964, there have been 4,437 confirmed
cases of SLE with an average of 193 cases per year (range 4 - 1,967). However,
less than 1% of SLE viral infections are clinically apparent and the vast
majority of infections remain undiagnosed. Illness ranges in severity from a
simple febrile headache to meningoencephalitis, with an overall case-fatality
ratio of 5-15 %. The disease is generally milder in children than in adults,
but in those children who do have disease, there is a high rate of
encephalitis. The elderly are at highest risk for severe disease and death.
During the summer season, SLE virus is maintained in a mosquito-bird-mosquito
cycle, with periodic amplification by peridomestic birds and Culex
mosquitoes. In Florida, the principal vector is Cx. nigripalpus, in
the Midwest, Cx. pipiens pipiens and Cx. p. quinquefasciatus
and in the western United States, Cx. tarsalis and members of the
Cx. pipiens complex.
Powassan (POW) virus is a flavivirus and currently the only well documented
tick-borne transmitted arbovirus occurring in the United States and Canada.
Recently a Powassan-like virus was isolated from the deer tick, Ixodes
scapularis. Its relationship to POW and its ability to cause human disease
has not been fully elucidated. POW's range in the United States is primarily in
the upper tier States. In addition to isolations from man, the virus has been
recovered from ticks (Ixodes marxi, I. cookei and Dermacentor
andersoni) and from the tissues of a skunk (Spiligale
putorius). It is a rare cause of acute viral encephalitis. POW virus
was first isolated from the brain of a 5-year-old child who died in Ontario in
1958. Patients who recover may have residual neurological problems.
Venezuelan equine encephalitis
Like EEE and WEE viruses, Venezuelan equine encephalitis (VEE) is an
alphavirus and causes encephalitis in horses and humans and is an important
veterinary and public health problem in Central and South America.
Occasionally, large regional epizootics and epidemics can occur resulting in
thousands of equine and human infections. Epizootic strains of VEE virus can
infect and be transmitted by a large number of mosquito species. The natural
reservoir host for the epizootic strains is not known. A large epizootic that
began in South America in 1969 reached Texas in 1971. It was estimated that
over 200,000 horses died in that outbreak, which was controlled by a massive
equine vaccination program using an experimental live attenuated VEE vaccine.
There were several thousand human infections. A more recent VEE epidemic
occurred in the fall of 1995 in Venezuela and Colombia with an estimated 90,000
human infections. Infection of man with VEE virus is less severe than with EEE
and WEE viruses, and fatalities are rare. Adults usually develop only an
influenza-like illness, and overt encephalitis is usually confined to children.
Effective VEE virus vaccines are available for equines.
Enzootic strains of VEE virus have a wide geographic distribution in the
Americas. These viruses are maintained in cycles involving forest dwelling
rodents and mosquito vectors, mainly Culex (Melanoconion)
species. Occasional cases or small outbreaks of human disease are associated
with there viruses, the most recent outbreaks were in Venezuela in 1992, Peru
in 1994 and Mexico in 1995-96.
Other arboviral encephalitides
Many other arboviral encephalitides occur throughout the world. Most of
these diseases are problems only for those individuals traveling to countries
where the viruses are endemic.
Japanese encephalitis (JE) virus is a flavivirus, related to SLE, and is
widespread throughout Asia. Worldwide, it is the most important cause of
arboviral encephalitis with over 45,000 cases reported annually. In recent
years, JE virus has expanded its geographic distribution with outbreaks in the
Pacific. Epidemics occur in late summer in temperate regions, but the infection
is enzootic and occurs throughout the year in many tropical areas of Asia. The
virus is maintained in a cycle involving culicine mosquitoes and waterbirds.
The virus is transmitted to man by Culex mosquitoes, primarily Cx.
tritaeniorhynchus, which breed in rice fields. Pigs are the main
amplifying hosts of JE virus in peridomestic environments.
The incubation period of JE is 5 to 14 days. Onset of symptoms is usually
sudden, with fever, headache and vomiting. The illness resolves in 5 to 7 days
if there is no CNS involvement. The mortality in most outbreaks is less than
10%, but is higher in children and can exceed 30%. Neurologic sequelae in
patients who recover are reported in up to 30% of cases. A formalin-inactivated
vaccine prepared in mice is used widely in Japan, China, India, Korea, Taiwan
and Thailand. This vaccine is currently available for human use in the United
States, for individuals who might be traveling to endemic countries.
Tick-borne encephalitis (TBE) is caused by two closely related flaviviruses
which are distinct biologically. The eastern subtype causes Russian
spring-summer encephalitis (RSSE) and is transmitted by Ixodes
persulcatus, whereas the western subtype is transmitted by Ixodes
ricinus and causes Central European encephalitis (CEE). The name CEE
is somewhat misleading, since the condition can occur throughout much of
Europe. Of the two subtypes, RSSE is the more severe infection, having a
mortality of up to 25% in some outbreaks, whereas mortality in CEE seldom
The incubation period is 7 to 14 days. Infection usually presents as a
mild, influenza-type illness or as benign, aseptic meningitis, but may result
in fatal meningoencephalitis. Fever is often biphasic, and there may be severe
headache and neck rigidity, with transient paralysis of the limbs, shoulders or
less commonly the respiratory musculature. A few patients are left with
residual paralysis. Although the great majority of TBE infections follow
exposure to ticks, infection has occurred through the ingestion of infected
cows' or goats' milk. An inactivated TBE vaccine is currently available in
Europe and Russia.
West Nile encephalitis
WNV is a flavivirus belonging taxonomically to the Japanese encephalitis
serocomplex that includes the closely related St. Louis encephalitis (SLE)
virus, Kunjin and Murray Valley encephalitis viruses, as well as others. WNV
was first isolated in the West Nile Province of Uganda in 1937 (2). The first
recorded epidemics occurred in Israel during 1951-1954 and in 1957. Epidemics
have been reported in Europe in the Rhone delta of France in 1962 and in
Romania in 1996 (3-5). The largest recorded epidemic occurred in South Africa
in 1974 (6).
An outbreak of arboviral encephalitis in New York City and neighboring
counties in New York state in late August and September 1999, was initially
attributed to St. Louis encephalitis virus based on positive serologic findings
in cerebrospinal fluid (CSF) and serum samples using a virus-specific
IgM-capture enzyme-linked immunosorbent assay (ELISA). The outbreak has been
subsequently confirmed as caused by West Nile virus based on the identification
of virus in human, avian, and mosquito samples. See also these MMWR articles
West Nile-Like Viral Encephalitis -- New York, 1999. MMWR,
West Nile-Like Viral Encephalitis -- New York, 1999. MMWR,
1999:48(39);890-2. A recent outbreak WN encephalitis occurred in Bucharest,
Romania in 1996.
The virus that caused the New York area outbreak has been definitively
identified as a strain of WNV. The genomic sequences identified to date from
human brain, virus isolates from zoo birds, dead crows, and mosquito pools are
identical. SLE and West Nile viruses are antigenically related, and cross
reactions are observed in most serologic tests. The isolation of viruses and
genomic sequences from birds, mosquitoes, and human brain tissue permitted the
discovery of West Nile virus in North America and prompted more specific
testing. The limitations of serologic assays emphasize the importance of
isolating the virus from entomologic, clinical, or veterinary material.
Although it is not known when and how West Nile virus was introduced into
North America, international travel of infected persons to New York or
transport by imported infected birds may have played a role. WNV can infect a
wide range of vertebrates; in humans it usually produces either asymptomatic
infection or mild febrile disease, but can cause severe and fatal infection in
a small percentage of patients. Within its normal geographic distribution of
Africa, the Middle East, western Asia, and Europe, WNV has not been documented
to cause epizootics in birds; crows and other birds with antibodies to WNV are
common, suggesting that asymptomatic or mild infection usually occurs among
birds in those regions. Similarly, substantial bird virulence of SLE virus has
not been reported. Therefore, an epizootic producing high mortality in crows
and other bird species is unusual for either WNV or SLE virus. For both
viruses, migratory birds may play an important role in the natural transmission
cycles and spread. Like SLE virus, WNV is transmitted principally by
Culex species mosquitoes, but also can be transmitted by Aedes,
Anopheles, and other species. The predominance of urban Culex
pipiens mosquitoes trapped during this outbreak suggests an important role
for this species. Enhanced surveillance for early detection of virus activity
in birds and mosquitoes will be crucial to guide control measures.