+++
CNS Arboviral Infections
++
Arboviral infections can lead to CNS disease of various forms,
most commonly including encephalitis, meningitis, and flaccid paralysis. CNS
manifestations are usually a rare outcome of infection, with the
majority of people developing these infections being asymptomatic
or having mild, nonspecific symptoms. This chapter is focued on
those infections that most commonly lead to CNS disease in North America
and touch on those that are most important
globally (tick-borne encephalitis and Japanese encephalitis viruses).
++
West Nile Virus (WNV) was originally discovered in 1937 in Uganda
and is maintained in an enzootic life cycle in birds of the Corvidae family
(crows, magpies, jays) via mosquito transmission3,8 (see eFig. 305.2). A variety of mosquito species
have been implicated, but Culex species have been
the more common vector involved in spread of WNV, particularly in
North America.3,9 Sporadic epidemics and epizootics
(spread within animal populations) were previously observed in Israel (1950s),
South Africa (1970s), Algeria, Morocco, Romania, Tunisia, Czech
Republic, Congo, Italy, Israel, Russia, and France (1990s), but
not in North America until 1999. That year, an outbreak of WNV encephalitis
cases was reported in New York City with a strain of virus that
was genetically indistinct from epidemic strains in Mediterranean
countries, suggesting introduction from that area of the world.
A simultaneous epizootic was noted in horses and birds at that time.
Since 1999, WNV has spread throughout North America and in 2007
was reported in all continental US states (eFig.
305.3) and in central and western Canada (Ontario, Manitoba, Saskatchewan,
and Alberta).10
++
++
++
While WNV infection occurs predominantly via arthropod transmission
to humans, there have also been rare reports of transmission via blood
transfusion, organ donation, and perinatal transmission from an
acutely infected mother.9 Screening of blood and
organ donors for WNV infection has been initiated in response to
these nosocomial transmissions. A seasonal pattern of transmission
from July to December has been noted yearly, with the bulk of transmissions
taking place during August and September.
++
After the host is bitten by an infected mosquito, the virus replicates
locally in tissue and lymph nodes before resulting in viremia and
sometimes crossing the blood-brain barrier to lead to neurologic
disease.9,11 The incubation period to development
of symptoms is 2 to 14 days but can be as long as 21 days in immunocompromised
patients.3,12,13 Only about 20% of individuals
will develop symptoms of infection; most of these will develop West
Nile Fever, while less than 1% will develop CNS manifestations.
West Nile Fever is characterized by abrupt onset of fever, headache, myalgia,
weakness, gastrointestinal symptoms (abdominal pain, nausea/vomiting, diarrhea),
and sometimes a transient maculopapular rash. Symptoms often last
several days and can be followed by a more prolonged period of fatigue
and weakness. Other nonneurologic manifestations that have rarely been
observed include hepatitis, pancreatitis, myocarditis, rhabdomyolysis,
orchitis, bladder dysfunction, and ocular manifestations such as
chorioretinitis, optic neuritis, and retinal hemorrhages.
++
CNS disease most commonly manifests as meningitis, encephalitis,
or flaccid paralysis.3,13,14 WNV meningitis produces
the usual symptoms of aseptic or viral meningitis, with fever, headache,
and neck stiffness, along with the above-mentioned West Nile Fever
symptoms; cerebrospinal fluid analysis often reveals a mild to moderate
lymphocytic pleocytosis, elevated protein, and normal glucose. WNV
encephalitis can be characterized by the additional findings of
altered sensorium, seizures, parkinsonian features (bradykinesia,
cogwheel rigidity, postural instability, and masked facies), and
other movement disorders such as myoclonus, intentional tremor, and
bruxism. Viral infection of the anterior horn cells can produce
a poliomyelitis-like presentation with an acute, symmetric, flaccid paralysis.
WNV infection has rarely been associated with Guillain-Barré syndrome.
Most patients with WNF or aseptic meningitis recover completely,
but patients with encephalitis or flaccid paralysis can be left
with residual deficits. The case fatality rate of neurologic disease
in adults is 5% to 9% but is less than 1% in
children.13,15
+++
ST. Louis Encephalitis
Virus
++
St. Louis encephalitis virus (SLEV) is found exclusively in the
western hemisphere and was the leading cause of epidemic flaviviral encephalitis
in the United States until the arrival of West Nile virus in the
last decade.3 It is found throughout continental
United States and parts of Canada (see eFig. 305.4).
SLEV was first recognized in 1933 in St. Louis, Missouri, and both
sporadic cases and focal outbreaks have been observed throughout
North America since that time. Similar to West Nile virus, SLEV
is maintained in a zoonotic life cycle, with birds as the definitive
host, and is transmitted to humans by the bite of Culex species
of mosquitoes in the late summer and early fall.
++
++
Less than 1% of SLEV infections are clinically apparent,
and 3 main clinical syndromes are observed: simple febrile headache,
meningitis, and encephalitis, with the risk of more severe and neuroinvasive
disease increasing with age. After an incubation period of 4 to
21 days, onset of symptoms begins with a flulike prodrome of fever,
headache, myalgia, fatigue, and sometimes respiratory or gastrointestinal
symptoms. As with West Nile virus, urological symptoms, including
dysuria, urgency, and incontinence, can also be seen in up to 25% of
patients.16 Those who develop meningitis usually
present with typical features of aseptic meningitis. Encephalitis
is most commonly associated with altered consciousness and confusion.
Other reported features have included generalized weakness without
focal findings, tremulousness, cerebellar signs, cranial nerve deficits,
abnormal movements (myoclonus, nystagmus), and, less commonly, epileptiform
activity.2,3
++
Laboratory findings with SLEV infection can include a moderate
cerebrospinal fluid mononuclear pleocytosis with elevated protein
and increased opening pressure, and hyponatremia can be seen as
part of the syndrome of inappropriate secretion antidiuretic hormone.17 Magnetic
resonance imaging can show high signal intensity in the substantia
nigra. An extended convalescence can be observed in up to half of
patients, characterized by asthenia, irritability, tremulousness,
sleep disturbance, depressive symptoms, memory loss, and headache.18 Overall
mortality is reported as 8% with much higher mortality
in the elderly (20%) and much lower in the pediatric population
(2%).
++
Powassan virus encephalitis occurs rarely. Since its discovery
in 1958 when it was isolated from the brain of a 5-year-old child
from Powassan, Ontario, who died of encephalitis, it has been found
to be a rare cause of encephalitis in North America. It is the only
tick-borne flavivirus in the Americas and is related to tick-borne
encephalitis virus from East Asia.2 While cases
of Powassan virus encephalitis have been reported throughout North America
and East Asia, overt human disease is felt to be restricted to southern
Canada and the northern tier of US states including Wisconsin,
Michigan, New York, and Maine (see Fig. 305-1).
Persons with a history of outdoor activity are most commonly affected
by this virus, but children have been disproportionately represented
in the known cases, with one report noting 85% of infections
occurring in persons under 20 years of age.
++
++
The clinical presentation of Powassan virus disease is not well
characterized because of the low number of cases reported.2 The
incubation period is at least 1 week from exposure. Reported prodromal
symptoms include sudden onset of illness with sore throat, fatigue, headache,
and high fever. Encephalitis cases may be characterized by vomiting,
prolonged fever, respiratory distress, lethargy, meningeal irritation,
and focal neurologic lesions. One reported case had temporal lobe
involvement typical of herpes encephalitis. Laboratory findings
include cerebrospinal fluid pleocytosis, initially polymorphonuclear
then lymphocytic, as well as normal glucose and elevated protein.
Sequelae, including neurologic abnormalities such as hemiplegia,
hypotonia, and spasticity, are common in survivors.
+++
Tick-Borne Encephalitis
Virus
++
Tick-borne encephalitis virus (TBEV) is not found in North America
but is the most important tick-borne arbovirus in Europe.3,19 It is
found in predominantly in Eastern Europe and Asia. A dramatic increase
in the number of cases has been seen in the last 3 decades, and
currently, approximately 13,000 people require hospitalization for
TBEV in Europe each year. Closely related to Powassan virus, 3 main
subtypes of TBEV have been identified: Far Eastern (previously Russian
spring-summer encephalitis), Siberian (previously west-Siberian
encephalitis), and European (previously Central European encephalitis). Some
countries have successfully instituted vaccination campaigns to
reduce incidence of this infection in at-risk populations, and the
need for pretravel vaccination is being increasingly recognized.
It is transmitted by ticks that parasitize a variety of bird and mammal
species; cases of transmission via ingestion of unpasteurized milk
from infected goats, sheep, or cattle have also been reported. Adult
males are most commonly affected, but children with outdoor exposures are
still at risk.
++
Few people infected with TBEV develop symptoms. Symptomatic patients
most often present in the summer months and report onset of illness
approximately 4 to 28 days after exposure (median 8 days).3 Illness
is biphasic, with the initial phase consisting of a nonspecific,
flulike illness with fever, malaise, headache, nausea, vomiting,
and myalgias lasting less than 1 week. Following resolution of these
symptoms, many patients enter a second phase of illness after 4
to 16 days (median 10 days) characterized by fever, vomiting, headache,
and meningeal signs. Four TBEV syndromes can occur during the second
phase: meningitis, meningoencephalitis, meningoencephalomyelitis,
and meningoradiculoneuritis; the former 2 entities are the most
common forms in children (approximately two thirds and one third
of cases, respectively) while the latter 2 are rarely encountered.20 The
most frequent signs noted with encephalitis include tremor (particularly of
the tongue and face), somnolence, and ataxia. Laboratory findings
typically include leukocytosis, elevated erythrocyte sedimentation rate,
and lymphocytic cerebrospinal fluid pleocytosis. While up to 30% of
adults may be left with residual neurologic sequelae and up to 2% may
die, children commonly fare better, with residual deficits seen
in 0% to 4% and few reported deaths.20-22 Children who
have suffered from TBEV infection are more likely to suffer from
impaired attention and psychomotor speed.
+++
Japanese Encephalitis
Virus
++
Japanese encephalitis virus (JEV) is the most important cause
of epidemic viral encephalitis worldwide, with 35,000 to 50,000
cases estimated annually and approximately 10,000 deaths.3 This
flavivirus is endemic and causes periodic epidemics throughout Southeast Asia,
China, and the Asian subcontinent, and has recently spread to parts
of Australia (see eFig. 305.5). Effective
vaccines against JEV have been available for decades and have been
incorporated into the childhood vaccination schedules of many Asian
countries, leading to dramatic reductions in encephalitis cases
in those countries. Meanwhile, the impoverished areas of Southeast
Asia still bear the burden of this disease.
++
++
JEV is transmitted via mosquitoes that are common in rice fields,
and the virus is maintained and amplified in pigs and aquatic bird populations.
Due to the association with rice fields and pig farming, rural areas
are most heavily affected, although cities with peripheral agricultural
development have also seen isolated cases or outbreaks. Most cases (99%)
are subclinical, leading to immunity in adolescents and adults,
and thus young, nonimmune children suffer the most symptomatic disease.
++
The incubation period of JEV disease ranges from 5 to 15 days,
often followed by a prodromal period of up to a week with nonspecific
symptoms including fever, nausea, vomiting, coryza, diarrhea, and
rigors.23 This is followed by the acute phase of
disease. While a minority of patients present with aseptic meningitis
or acute flaccid paralysis, the majority of those diagnosed with
JEV infection have encephalitis. Fever, headache, and altered sensorium
(ranging from disorientation to coma) are common and may be accompanied
by or may lead to seizures. Other common features include weakness,
masklike facies, tremor, generalized hypertonia, cogwheel rigidity,
and cranial nerve abnormalities. Neuropsychiatric symptoms, such
as mutism in children or abnormal behaviors in older children or
adults, may be present. The subacute and convalescent stages manifest
a varying degree of neurologic involvement, with focal seizures
or asymmetric paralysis, extrapyramidal signs, and rapidly changing central
nervous system signs. Approximately 25% of cases are fatal
because of neurologic morbidity of acute infection or complications arising
over the course of the illness.3 Young children
are more likely to succumb to JEV infection, and survivors have
neurologic sequelae in one third of cases.23 These
can include impaired cognition, behavioral disturbances, seizure
disorders, gait or coordination abnormalities, and psychologic deficits.
Treatment is supportive.
+++
Eastern Equine
Encephalitis Virus
++
Eastern equine encephalitis virus (EEEV) is an alphavirus that
was first described in the 1930s following outbreaks in the northeastern United
States of encephalitis in horses and then in children and adults.
In the United States, its geographic distribution includes the Eastern
seaboard and Gulf states as well as some inland foci of disease
(New York, Georgia, Michigan, and Indiana); Canada and Central and
South America have also reported cases18 (see eFig. 305.6). EEEV is maintained in
its natural life cycle by transmission between mosquitoes and native
bird species and has been most associated with swampy areas.5 The
virus affects humans and horses only via bridging species of mosquitoes,
which bite both birds and humans. When humans are infected, those
over age 50 and younger than 15 years are at greatest risk of developing
severe EEEV disease.24
++
++
EEEV is distinct from other arboviruses in its propensity to
result in fulminant neurologic illness or death, particularly in
infants and young children. The incubation period from mosquito
bite to development of disease is 3 to 10 days. Prodromal symptoms
of fever, headache, confusion, lethargy, myalgias, and gastrointestinal
symptoms precede the onset of neurologic symptoms by 5 to 10 days.2,5 This is
followed by neurologic symptoms such as seizures, nuchal rigidity,
altered mental status, muscle twitching or fibrillation, tremors,
spasticity, paralysis, and cranial nerve palsies. Rapid progression
to coma is possible. Features that may be noted specifically in
infants and young children include a short or absent prodrome, fever,
altered mental status, seizures, vomiting, cyanosis, and periorbital
and upper extremity edema.18 Cerebrospinal fluid lymphocytic
pleocytosis, elevated protein, and increased opening pressure are
characteristic, and hyponatremia due to secretion antidiuretic hormone
can be seen. Electroencephalogram demonstrates diffuse slowing consistent
with generalized encephalitis, and magnetic resonance imaging can
delineate focal lesions in the basal ganglia, thalami, and brainstem.
In those who do develop encephalitis, it is typically a fulminant illness
leading to coma or death in 30% to 70% of individuals,
with the highest mortality rates seen in infants and young children.
One third to one half of survivors are left with severe neurologic
sequelae such as mental retardation, behavioral changes, convulsive
disorders, and paralysis; rapid progression to coma, hyponatremia,
and high cerebrospinal fluid white blood cell count (> 500 cells/mm3)
are poor prognostic factors.18,25
+++
Western Equine
Encephalitis Virus
++
Western equine encephalitis virus was first described as a cause
of viral encephalitis in horses and subsequently in humans in the 1930s.2 Its
distribution has been described in US states and Canadian provinces
west of the Mississippi River (see eFig. 305.7)
as well as in countries in South America.5 Cases
typically present in summer in irrigated areas of agriculture. Like
other arboviruses, it is maintained in passerine bird populations
in whom infection is often inapparent. Most human infections are
asymptomatic or nonspecific febrile illnesses that do not result
in seeking medical attention; the ratio of infection to symptomatic
illness is low, reported as less than 1000:1. The exception is in
infants, where the ratio is much higher, reported as being nearly
1:1. Most cases are reported in the summer months, with risk factors
for infection being male sex, rural residence, and outdoor employment
in farming. Transplacental transmission has been reported when the
mother’s infection has occurred within days of delivery.18
++
++
Western equine encephalitis virus disease is characterized by
an incubation period of 2 to 10 days and subsequent onset of a short
prodrome of 1 to 4 days.5 Symptoms during the prodrome
are similar to those of eastern equine encephalitis virus, including
fever, intense headache, nausea, vomiting, and, occasionally, respiratory
symptoms. CNS infection is characterized by lethargy, depressed level
of consciousness, nuchal rigidity, photophobia, and vertigo.2,5 Infants
with Western equine encephalitis virus typically have irritability,
seizures, tense fontanel, rigidity, upper motor neuron deficits,
and tremors. Children and adolescents may display muscular rigidity/spasticity,
tremors, involuntary movements, hyporeflexia, and paralysis. Investigations
reveal findings similar to those of eastern equine encephalitis
virus but often milder. Cerebrospinal fluid pressure and protein
may be slightly elevated, with a lymphocytic pleocytosis in older
children and adolescents or polymorphonuclear pleocytosis in infants.
Neurologic sequelae are seen in 30% or more of infants
and young children, while the rate in adults is much lower; sequelae
can include fatigue, irritability, headache, tremors, and motor
and intellectual deficits. The overall case fatality rate is approximately
3%.
+++
Venezuelan Equine
Encephalitis Virus
++
Venezuelan equine encephalitis virus was first described in the
1930s and has since been described largely as a cause of epizootics
of encephalitis in horses in South and Central America, sometimes
with coincident human coepidemics.5 The largest
of these began in 1969 in El Salvador and Guatemala and spread throughout
Mexico and into Texas by 1971. Since then, Venezuelan equine encephalitis
virus has rarely been reported as a cause of encephalitis in southern
US states despite the persistence of an endemic focus of infection
within the Florida Everglades.2 Unlike the other
equine encephalitis viruses, horses and humans develop significant
viremia during infection, which could make them more than simply “dead-end” hosts
due to the possibility of a mosquito acquiring the infection from
a horse or human and then transmitting it to a new host.26 Transmitted
by multiple mosquito species (Culex, Aedes, Mansonia, Psorophora, and Deinocerites species),
the virus is maintained in small mammal populations.
++
Human disease with Venezuelan equine encephalitis virus is most
often asymptomatic or mildly symptomatic with a nonspecific viral illness,
though the risk of significant infection is highest in children.5 Symptoms
begin after an incubation period of 1 to 6 days and include fever,
malaise, chills, myalgia, headache, photophonophobia, hyperesthesia,
and vomiting. Approximately 4% of children and fewer than 1% of
adults progress to severe encephalitis within 7 days of onset of
prodrome, and common features include nuchal rigidity, ataxia, seizures,
coma, and paralysis. Cytopenias (lymphopenia, neutropenia, and thrombocytopenia)
and liver enzyme abnormalities, as well as lymphocytic cerebrospinal
fluid pleocytosis, may be observed.
+++
California Encephalitis
Viruses
++
California encephalitis is CNS disease caused by one of a group
of related viruses in the Bunyavirus genus. The most common of these
is La Crosse encephalitis virus (LACV), while other less common
members include California virus (found in California), Jamestown
Canyon virus (found throughout US mainland, Canada, and Alaska),
and snowshoe hare virus (found in parts of both the United States
and Canada)6,18 (see eFig. 305.8).
LACV was first isolated in 1965 from brain tissue from a 4-year-old
child in La Crosse, Wisconsin.27 Its geographic
distribution has since been recognized to include predominantly
the upper midwestern states of Ohio, Indiana, Illinois, Iowa, Wisconsin,
and Minnesota, and less predominantly, the mid-Atlantic and southeastern
areas of the United States.6 The recent introduction
to North America of Aedes albopictus (another mosquito
capable of transmitting LACV) may further extend the geographic
range of this disease beyond the eastern United States. The natural
hosts for this virus are small mammals, including squirrels and
chipmunks. Cases typically occur in summer and autumn months.
++
++
Symptomatic infection is very uncommon in LACV, but those who
develop symptoms are almost all in the pediatric age group, particularly
school-aged children.18 A
male predisposition has been found, and proximity to forested areas
or artificial mosquito habitats (discarded tires or containers)
is a risk factor. The incubation period is 5 to 15 days. Symptomatic
infection is usually an encephalitis syndrome, while meningitis
or meningoencephalitis are less common presentations.27 Symptoms
include fever, headache, vomiting, meningism, seizures, and disorientation;
focal neurologic symptoms are seen in up to 25%. A lymphocytic
pleocytosis of 200 cells/mL or less is most often observed
with normal glucose and infrequently elevated protein. Hyponatremia
can be present due to secretion of antidiuretic hormone. Neurologic sequelae
such as seizure disorders, cranial nerve palsies, or hemiparesis
may be present in up to 12% of children, while more subtle problems
such as cognitive dysfunction and neurobehavioral abnormalities
may be more common. Death occurs in less than 1% of those
diagnosed with LACV disease.
++
Colorado tick fever virus (CTFV) is a member of the Coltivirus
genus and is found in the western United States and southwestern
Canada, particularly in the Rocky Mountain region.7 The
greatest numbers of cases have been reported in Colorado, Utah,
Wyoming, and Montana. Disease distribution corresponds to that of
the major vector of CTFV, the wood tick (Dermacentor andersoni), which
prefers mountainous terrain from 4000- to 10,000-foot elevations. Other
species of ticks have also been implicated. The virus is known to
be transmitted transtadially (between life stages) in the tick,
becoming infected in its larval stage but only capable of transmitting
to humans in the adult stage.28 Unlike some other
arboviruses, CTFV is not transmitted transovarially (from adult
female to egg). Multiple natural CTFV-amplifying hosts are known
to exist, including ground squirrels, chipmunks, marmots, and other mammals.
Outdoor exposure is an obvious human risk factor for disease, and
a male predominance has been noted. Vertical transmission from mother
to fetus has been reported.7
++
The mean incubation period from exposure to infection is 3 to
4 days, with a range from less than 1 day to 14 days.7 An
abrupt onset of illness with symptoms of fever, chills, malaise,
myalgia, headache, hyperesthesia, and retro-orbital pain lasting
up to 1 week is common, followed by remission of symptoms. Less common
findings include conjunctivitis, pharyngitis, lymphadenopathy, splenomegaly, and
a papular or petechial rash. Recurrence of symptoms 2 to 3 days
later is seen in up to half of cases, giving rise to a diphasic
or “saddleback” fever curve. CTFV disease is complicated
by CNS manifestations in 5% to 10% of cases, predominantly
aseptic meningitis and rarely encephalitis; neurologic manifestations and
other severe forms of CTFV disease are more common in younger age
groups. Other rare complications of CTFV infection can include pericarditis,
myocarditis, orchitis, pneumonia, and hepatitis.
++
Laboratory findings commonly include leucopenia and thrombocytopenia
(which can sometimes be severe).7 CTFV infects
erythroblasts, and the persistence of viremia for up to weeks or
months after onset of illness parallels the survival time of red
blood cells sheltering the virus. Viral culture methods and molecular diagnostics
can thus be used to diagnose disease in addition to the usual serologic
methods of diagnosing arboviral infection.
+++
Rash/Arthralgia Arboviral
Infection Syndromes
++
A number of arboviral infections can lead to syndromes that present
with prominent symptoms of rash and/or arthralgia. None
of these, however, are endemic to North America, although imported
cases are becoming more common. Alphaviruses are the most common group
of arboviruses causing rheumatologic complaints, but pediatric infection
less commonly leads to arthralgias or arthritis than does adult
infection. These viruses are listed in Table
305-1.
++
Chikungunya virus is an alphavirus that causes infection in tropical
locales, including South Asia (India, Sri Lanka), Southeast Asia (Thailand,
Cambodia, Vietnam, the Philippines, and Indonesia), islands of the
Indian Ocean, and throughout Africa.29 While it
is not endemic in the United States, 37 imported cases were reported
in 2006 relating to outbreaks in India and islands in the Indian Ocean.30 It
is transmitted by numerous species of Aedes mosquitoes,
which can inhabit both rural and urban environments. Primates, rodents,
and birds are the main reservoirs, although humans can also serve
as reservoirs during epidemic periods.
++
The incubation period for Chikungunya virus is usually 2 to 4
days (though it can range from 1 to 12 days), followed by abrupt
onset of illness including high fever, headache, back pain, myalgia,
and arthralgia.29 The arthralgia can be severe
and mainly affects small joints of the extremities (wrists, ankles,
phalanges) but can also involve larger joints. Swelling of joints
may also be noted, and articular symptoms can last from 1 week up
to months or years, though children rarely have severe or relapsing
symptoms. Rash is noted in up to half of cases, including maculopapular
eruption of the thorax, facial edema, bullous lesions with sloughing,
or petechiae with bleeding gums; the latter 2 findings are particularly
noted in children. Hemorrhagic symptoms are rarely noted, and children
occasionally present with CNS symptoms such as seizures. Neonatal
infections from mothers infected prior to delivery have been observed. Leukopenia
and elevated inflammatory markers (C-reactive protein, erythrocyte
sedimentation rate) are common laboratory findings
++
Ross River virus (RRV) is another alphavirus responsible for
epidemic polyarthritis in Australia, Papua New Guinea, and islands
of the South Pacific.31 Although recognized as
an arbovirus similar to Chikungunya virus and others, RRV was only
isolated in 1972 from the serum of a 7-year-old aboriginal boy.
Thousands of cases of epidemic polyarthritis caused by RRV and the
closely related Barmah Forest virus are reported in Australia each
year. RRV is transmitted by the bite of species of Aedes and Culex mosquitoes,
and marsupials (kangaroos and wallabies) and small mammals are the
natural hosts. Humans and horses are also thought to play a role
in epidemic spread and maintenance of RRV.
++
The incubation period for this illness is 7 to 9 days but can
range from 3 to 21 days.31 Constitutional symptoms
of fever, myalgia, sore throat, lymphadenopathy, and coryza may
be observed. Rash is present in half of patients, usually maculopapular
but sometimes vesicular or purpuric; the extremities, including palms,
soles, digits, and face, are affected. Acute onset of joint symptoms,
including arthralgias, joint tenderness, warmth, redness, swelling,
and restriction of movement is prominent with RRV, with symmetric
involvement of peripheral joints being most common (especially ankles,
knees, wrists, hands, and fingers). Symptoms may be intense and
prolonged, sometimes extending beyond the acute infection period.
Rare cases of meningitis, encephalitis, and glomerulonephritis have
been reported. In general, symptoms of infection are less common
and less severe in children than in adults, and deaths are extremely
rare.