Jason Brophy and Elizabeth Lee Ford-Jones
Arboviruses (or arthropod-borne viruses) are a heterogeneous group of viruses that share the same usual route of entry into humans: via the bite of an infected mosquito, tick, sandfly, or other arthropod.1,2 The life cycle of most arboviruses is characterized by the ability of the virus to replicate in both an arthropod vector and a vertebrate “natural” host (usually birds or small mammals) and by transmission between these two organisms at the time of the arthropod’s bite (eFig. 305.1 ). This cycle leads to establishment or maintenance of the virus in a given ecosystem. Humans or domestic animals are only “incidental” hosts for many species of arboviruses, as infection in such hosts (although capable of causing disease) is often a dead-end for the virus due to viremia being too low or too transient to contribute to maintenance of the cycle of transmission. Some viruses are specific to a single genus or species of insect, while others are transmissible by multiple vectors. In addition, some arthropods are capable of transovarial transmission, wherein their eggs (which sometimes overwinter and hatch in spring) are infected with the virus, allowing viral maintenance in areas of colder climate.
Arboviruses generally produce 1 of 4 clinical syndromes: (1) central nervous system (CNS) disease, (2) febrile illness with rash, (3) arthropathy, or (4) hemorrhagic fever syndrome.1 In North America, encephalitis is the most commonly diagnosed manifestation of arboviral infection, with several viruses producing sporadic disease as well as outbreaks of infection each year. Table 305-1 provides a list of arboviruses presenting with different symptom complexes, and details the vector, reservoir, distribution, incubation period, and the population most affected.
CLASSIFICATION OF ARBOVIRUSES
The term arbovirus refers only to viruses in which the mode of infection is by the bite of an infected arthropod. This artificial grouping includes dozens of viruses from a number of different families and genera, including mainly the Flavivirus genus, the Alphavirus genus, the Bunyaviridae family, and the Reoviridae family (Coltivirus genus). These viruses differ phylogenetically and structurally but nonetheless produce similar types of illness.
These are a large group of viruses with worldwide distribution, over 30 of which cause disease in humans.3,4 The prototype of the genus is yellow fever virus, from which the genus name is derived (flavusbeing Latin for “yellow”). Eight antigenic groupings have been found, the most important of which are the Japanese encephalitis complex (which includes Japanese encephalitis, St. Louis encephalitis, West Nile, and Murray Valley fever viruses); the dengue complex (dengue viruses 1–4); the tick-borne virus complex (Central European encephalitis [more recently renamed tick-borne encephalitis], Russian spring-summer encephalitis, louping-ill, Powassan, Kyasanur Forest disease, and Omsk hemorrhagic fever viruses); and yellow fever virus.
These are a genus within the Togaviridae family and include a number of medically important arboviruses.5 These can be roughly divided into New World alphaviruses, which cause CNS disease and include eastern equine, western equine, and Venezuelan equine encephalitis viruses, and Old World alphaviruses, which are more likely to cause syndromes of fever, rash, and arthropathy (Chikungunya, O’nyong-nyong, Mayaro, Ross River, Sindbis, and Barmah Forest viruses).
This family includes multiple arthropod-borne viruses as well as viruses transmitted by other modes.6 The main arboviral genera in the Bunyaviridae include the Bunyavirus genus (including the California encephalitis group: La Crosse, California, and Jamestown Canyon viruses); the Phlebo-virus genus (which includes Rift Valley fever virus and Toscana virus); and the Nairovirus genus (which includes Crimean-Congo hemorrhagic fever virus). The Hantavirus genus is also in this family; however, these viruses (which cause pulmonary syndromes as well as hemorrhagic fever with renal syndrome) are transmitted via direct inhalation of rodent excreta or urine rather than by arthropod bite.
These are a genus within the Reoviridae family, which also includes the well-known rotavirus member.7 Coltivirus arboviral species include Colorado tick fever virus as well as a number of other rare members (Salmon River virus, Eyach virus, and Asian members of the Seadornavirus genus such as Banna and Beijing viruses).
SYNDROMES CAUSED BY ARBOVIRUSES
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
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 ). 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
Table 305-1. Arboviruses of Importance in North America and Globally
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 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 Guil-lain-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.2While 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.
FIGURE 305-1. Human Powassan cases by state, 2001–2007. (Source: Centers for Disease Control and Prevention. Division of Vector Borne Infectious Diseases. http://www.cdc.gov/ncidod/dvbid/Arbor/images/POW_Map.jpg. Accessed September 11, 2008.)
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. 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.
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).3Illness 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.18Cerebrospinal 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 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
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.5Symptoms 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
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.
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 erythro-blasts, 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 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 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. 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.
Ross River Virus
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.
ARBOVIRAL HEMORRHAGIC FEVER SYNDROMES
Viral hemorrhagic fever infections are caused by a large group of viruses discussed in Chapter 307 and summarized in Table 307-1. Arboviral causes include members of the flavivirus (yellow fever, dengue, Omsk hemorrhagic fever, and Kyasanur Forest disease viruses) and bunyavirus (Congo-Crimean hemorrhagic fever and Rift Valley fever viruses) groups.
For most of the arboviruses discussed, diagnosis relies on detection of IgM and IgG antibodies in serum and/or cerebrospinal fluid. Viral isolation has traditionally been used in the past and remains the most definitive method of diagnosis.1 Serologic cross-reactivity among members of the different families (particularly the flaviviruses) has been noted, making diagnosis difficult in children coming from areas endemic for other members of the same group.3Molecular methods (such as polymerase chain reaction or nucleic acid amplification) have been developed for some viruses, but these techniques are not always readily available.1 Decisions regarding the best diagnostic assay should be made in discussion with institutional microbiologists.
Given the recent emergence of WNV into North America, its diagnosis warrants a more detailed discussion. Diagnosis of WNV infection is dependent on serologic or molecular evidence of infection in the setting of appropriate epidemiologic exposure. The serologic diagnosis of WNV infection is complicated by flavivirus antibody cross-reactivity as well as by the prolonged presence (up to 1 year or more) of WNV-specific IgM after acute infection.13 The best approach is to demonstrate a 2-fold increase in WNV-specific antibody between acute and convalescent serum samples collected 2 to 3 weeks apart. Demonstration of WNV IgM in cerebrospinal fluid can help confirm CNS infection, while viral culture and nucleic acid amplification tests for WNV ribonucleic acid performed on serum, cerebrospinal fluid, and tissue can also be diagnostic.
PREVENTION OF ARBOVIRAL INFECTION
Vaccines for yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus have been in usage for a number of years, but human vaccines for other arboviruses are not yet available.3
In the past, vector control programs have been highly successful in controlling arboviruses such as yellow fever virus; however, the resurgence of a number of arboviruses worldwide has not been met with renewed efforts at vector control. During local outbreaks of arboviruses, there may be a role for pesticide use or other attempts to reduce vector populations such as removal of reproductive habitats.1 Personal protective measures to avoid exposure should be encouraged to avoid arthropod bites/exposures, such as application of insect repellant, wearing of light-colored clothing with long sleeves and pants, use of screens to keep insects out of dwellings, and prompt removal of ticks when found on children playing outdoors.