Chikungunya Fever

Official reprint from UpToDate

www.uptodate.com 2015 UpToDate

AuthorMary Elizabeth Wilson, MD

Section EditorMartin S Hirsch, MD

Deputy EditorElinor L Baron, MD, DTMH

Chikungunya fever

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jul 2015. | This topic last updated: Mar 26, 2015.

INTRODUCTION Chikungunya is an arthropod-borne virus (arbovirus) endemic to West Africa that causes acute

febrile polyarthralgia and arthritis. The name chikungunya is derived from a local language of Tanzania meaning

"that which bends up" or "stooped walk" because of the incapacitating arthralgia caused by the disease.

Multiple outbreaks beyond West Africa have been described. Since 2004, chikungunya has spread broadly, causing

massive outbreaks with explosive onset in the Indian Ocean region, India, and other parts of Asia [1-3]. Chikungunya

had traditionally been perceived as a tropical disease until an outbreak in Italy in 2007. In addition, thousands of

cases have been identified in travelers returning from outbreak areas [4]. The distribution of mosquito vectors

capable of transmitting chikungunya virus is wide; since late 2013, chikungunya virus infections have spread widely

in the Americas [5].

EPIDEMIOLOGY The United States Centers for Disease Control (CDC) maintains a page with reported current or

previous local transmission of chikungunya virus.

Endemic areas Chikungunya virus is endemic in parts of West Africa, where it appears to be maintained in a

cycle involving humans, Aedes mosquitoes, primates, and perhaps other animals [6,7]. Serosurveys of humans in

parts of West Africa have identified antibodies to chikungunya virus in 35 to 50 percent of the population in the

absence of recognized outbreaks.

Spread and resurgence Chikungunya virus spreads by means of travel of infected individuals between regions

where competent mosquitoes exist for perpetuation of local transmission [8]. Imported cases have been described in

many Asian and European countries as well as in the Americas and Australia [9-16]. Rapid spread in the last few

years may also be related to a viral mutation that enhances replication efficiency in the Aedes albopictus mosquito.

(See 'Transmission' below and 'Mutation of virus and vector replication' below.)

After chikungunya virus was identified during an outbreak in East Africa in Tanzania in the early 1950s, the virus was

noted to be the cause of multiple outbreaks in many countries of central, southern, and western Africa. Outside

Africa, the first documented chikungunya fever outbreak was in Thailand in 1958. This was followed by outbreaks in

multiple other Asian countries, including India, Sri Lanka, Malaysia, Indonesia, Cambodia, Vietnam, Myanmar, the

Philippines, and Pakistan.

After a period of relatively little chikungunya activity, large outbreaks were observed in Africa in the late 1990s. In the

Democratic Republic of the Congo, for example, an urban outbreak involved an estimated 50,000 people in 1999 to

2000. Epidemics also occurred in Indonesia in 2001 to 2003 after decades without obvious chikungunya fever cases.

Indian Ocean and Asia Rapid spread of chikungunya virus has been observed in outbreaks involving the Indian

Ocean islands, where attack rates have been extremely high in previously unexposed populations. A massive

outbreak in Lamu (an island off the coast of Kenya) affected thousands in 2004; a seroprevalence study suggested

that the widespread epidemic may have affected 75 percent of the island's 18,000 inhabitants [17]. The epidemic on

Reunion Island in 2005 to 2006 involved approximately 266,000 individuals (34 percent of the island's population); a

higher attack rate was observed among older adult residents [18]. In the Comoro Islands, a seroprevalence study

found 63 percent positive for chikungunya virus antibodies [19].

In India, nearly 1.4 million cases of chikungunya fever were reported in 2006, and outbreaks have continued to

occur. The appearance and spread of chikungunya virus in India was observed after a hiatus of almost 32 years

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[20,21]. Chikungunya virus also reappeared in Malaysia in 2006 [22], in Thailand in 2008, in Singapore in 2008, and

caused an outbreak in Guangdong Province, China, in 2010 [23].

Europe Although chikungunya fever has traditionally been considered a disease of tropical and subtropical

regions, in the summer of 2007, chikungunya virus caused an outbreak in northeastern Italy [24]. The index case

was a traveler from India who became ill while visiting Italy, and phylogenetic analysis of the virus demonstrated

similarity with chikungunya strains found in the Indian Ocean outbreaks.

Between July and September 2007, 205 cases of chikungunya fever were identified in Italy by epidemiologic and

clinical criteria; 175 cases were confirmed by laboratory testing. The clinical attack rate in the two affected Italian

villages was 5.4 and 2.5 percent but increased with age (1.6 percent for residents

populations of Ae. albopictus may be more anthropophilic (eg, preferring human blood) than others; in some

settings, humans may be the most abundant host [37].

Ae. albopictus has become widely dispersed beyond Asia; it is now established in many parts of the Americas,

Europe, Africa, and the Pacific Islands [38]. In the United States, Ae. albopictus is found in southeastern and

mid-Atlantic states as well as in parts of the Southwest, Northeast, and lower Midwest [31]. Ae. albopictus has been

found as far north as New Jersey, southern New York, and Pennsylvania, but, with climate change, its range is

predicted to spread farther north [39].

Modes of mosquito dissemination include transport of mosquito larvae and eggs in used tires by container ships and

air traffic with subsequent establishment in new areas with suitable environmental and climatic conditions [40,41].

Outbreaks of chikungunya fever in Italy and Reunion have resulted from virus transmission by Ae. albopictus [24,37].

Subsequently simultaneous outbreaks of chikungunya fever and dengue infections have been documented in

Central Africa (Gabon) in association with the introduction of the Aedes albopictus vector. Dengue-chikungunya

coinfections have been documented in humans and in a wild-caught mosquito [42].

Mosquito competence Mosquito susceptibility to infection by chikungunya virus and mosquito competence

for virus transmission can vary [43]. Among Ae. aegypti and Ae. albopictus strains in Florida evaluated for

susceptibility to infection by and competence for transmission of a chikungunya virus from the Reunion outbreak, all

mosquitoes were susceptible to infection and capable of transmitting the virus [44]. Thus, local mosquitoes possess

the capacity to serve as vectors for transmission of chikungunya virus in Florida.

Similarly, Ae. albopictus collected in southern France demonstrated high susceptibility to infection with chikungunya

virus (77.1 percent), which was comparable to the susceptibility of mosquitoes collected from Reunion [45]. Given

the wide distribution of mosquito vectors capable of transmitting chikungunya virus, in the future, transmission could

occur in regions with no prior case reports [5].

Seasonal synchrony In order for a viremic traveler to initiate a local outbreak in a nonendemic area, there

must be seasonal synchrony between the geographic source of ongoing viral transmission and the geographic

destination vulnerable to introduction of infection (due to infestation with competent mosquito vectors) [46]. For

example, transmission of chikungunya virus in Italy during the summer of 2007 was successful because of presence

of virus in an individual traveling within the northern hemisphere between India and Italy; the period of active

transmission in India coincided with Italy's hottest months. Spread from the southern to northern hemisphere is less

likely because the warm seasons and vector activity for these regions may not be synchronous.

Extrinsic incubation period The extrinsic incubation period is the period between a mosquito blood meal

from a viremic host and the transmission of virus to a new host. During this period, the virus must replicate and

reach the mosquito salivary glands so that it will be transmitted to a new host when the mosquito takes the next

blood meal. The extrinsic incubation period varies depending on the virus, the mosquito vector, and environmental

conditions including temperature and humidity. In general, the warmer the temperature, the shorter the extrinsic

incubation period and the sooner the mosquito can transmit virus to a new host. In cool temperatures and in many

temperate areas, a mosquito may die before the extrinsic incubation period is complete.

The mutation in the chikungunya virus strain that caused the massive outbreak on Reunion (described below) may

also be capable of shortening the extrinsic incubation period, allowing more mosquitoes to survive long enough to

transmit virus [47]. (See 'Mutation of virus and vector replication' below.)

Nosocomial and vertical transmission Additional modes of transmission include nosocomial and vertical

transmission. Nosocomial transmission has been described in France, where a nurse was infected by exposure to

blood while caring for a patient infected in Reunion [9,11]. Transmission via transfusion of blood products and/or

organ transplantation could also occur, since chikungunya viremia (may exceed 10 RNA copies/mL plasma) is likely

prior to onset of symptoms [11,48]. Chikungunya virus infects the human cornea and could be transmitted via

corneal grafts. Infected corneas have been documented in individuals in the absence of systemic symptoms of

chikungunya infection [49].

9


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Vertical transmission of chikungunya has been described in Reunion; among 39 women in the outbreak with viremia

at the time of delivery, the rate of vertical transmission was 48.7 percent [50]. Symptoms among neonates were

observed within three to seven days and included fever, poor feeding, and rash; 89 percent had thrombocytopenia.

Among 19 infected neonates, 10 had severe disease, primarily encephalopathy. Caesarean delivery was not

protective against vertical transmission.

There is no evidence of congenital infection in infants who were exposed in utero [51].

VIROLOGY Chikungunya is a single-stranded RNA virus of the genus Alphavirus (Togaviridae family). It was first

isolated from mosquitoes and humans during an outbreak in Tanganyika (Tanzania) in 1952 to 1953 [52]. Thus far,

three lineages distinguishable by genotypic and antigenic characteristics have been identified: the clusters of Central

and East Africa, West Africa, and Asia.

Other alphaviruses that cause illnesses associated with fever and arthralgia or arthritis include O'nyong-nyong (East

and Central Africa), Barmah and Ross River viruses (Australia and the Pacific), Semliki virus (Africa), Mayaro virus

(South America), and Sindbis group viruses (widespread excluding the Americas) [27,53]. (See "Specific viruses that

cause arthritis".)

The pathogenesis of the severe and persistent joint symptoms that characterize chikungunya virus infections is

uncertain. Some data suggest that macrophage-derived products such as tumor necrosis factor-alpha, interferon-

gamma, and macrophage chemoattractant protein-1 may play important roles in the joint tissue damage [54].

Mutation of virus and vector replication The replication efficiency of chikungunya virus within the Ae.

albopictus mosquito may be enhanced in the presence of a mutation in the viral gene encoding the envelope protein

of the virus (mutation A226V). This mutation was observed in >90 percent of viral sequences in the latter period of

the Reunion outbreak, although it was not observed in the initial outbreak strains, suggesting an enhanced survival

benefit for this mutant (A226V) [55]. The mutation was also found in chikungunya virus isolates from the outbreak in

Italy [56].

The presence of this mutation has been associated with enhanced Ae. albopictus susceptibility to infection and more

rapid viral dissemination into the mosquito salivary glands [47]. As a result, a lower level of human viremia is

required for transmission of this mutant virus to a biting mosquito, facilitating the cycle of infection.

CLINICAL MANIFESTATIONS

Acute infection Clinical signs and symptoms begin abruptly with fever and malaise following an incubation

period of two to four days (range 1 to 14) [57].

Fever may be high grade (40C); the usual duration of fever is three to five days (range 1 to 10 days). Polyarthralgia

begins two to five days after onset of fever and commonly involves multiple joints (often 10 or more joint groups)

[9,21,58,59]. Joints affected include hands (50 to 76 percent), wrists (29 to 81 percent), and ankles (41 to 68

percent). Arthralgia is symmetrical in 64 to 73 percent and involves distal joints more than proximal joints.

Involvement of the axial skeleton was noted in 34 to 52 percent of cases. Pain may be intense and disabling, leading

to immobilization.

Skin manifestations have been reported in 40 to 75 percent of patients [21,59]. The most common skin manifestation

is macular or maculopapular rash (usually appearing three days or later after onset of illness and lasting three to

seven days). The rash often starts on the limbs and trunk, can involve the face, and may be patchy or diffuse.

Islands of normal skin may be seen along with the diffuse rash. Pruritus has been reported in 25 to 50 percent of

patients in some series. Bullous skin lesions have also been described, most often in children. Hemorrhagic

manifestations are uncommon.

Additional manifestations may include headache, myalgia, and gastrointestinal symptoms.

On physical examination, periarticular edema or swelling has been observed in 32 to 95 percent of cases. In one

series, large joint effusions were noted in 15 percent of cases. Peripheral lymphadenopathy (most often cervical)


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may be present (9 to 41 percent of cases) [10,60]. Conjunctivitis may be observed [61].

The most common laboratory abnormalities are lymphopenia and thrombocytopenia. Liver enzymes may be

elevated.

Persistent symptoms Following acute illness (usually lasting 7 to 10 days), some patients may experience

persistent signs and symptoms including arthritis/arthralgia, edematous polyarthritis of fingers and toes, morning

pain and stiffness, and severe tenosynovitis (especially of wrists, hands, and ankles) [62]. Carpal tunnel syndromes

may result from hypertrophic tenosynovitis. In addition, patients may report joint or bone pain at sites of previous

injury. Occasionally, unusual joints (such as sternoclavicular or temporomandibular joints) are involved. New onset

Raynaud phenomena in the second or third month following infection have been described in up to 20 percent of

cases [58]. Cryoglobulinemia has also been found in patients with persistent symptoms attributed to chikungunya

infection, >90 percent in one series [63].

Chronic symptoms usually involve joints affected during the acute illness and can be relapsing or unremitting and

incapacitating. Study with detailed analysis found arthralgias were typically polyarthralgia [64]; 63 percent had

associated local swelling.

The duration of persistent symptoms is variable. Among 47 patients with acute chikungunya fever followed in

Marseilles, France, 82 percent had persistent joint symptoms. At one, three, and six months following acute illness,

symptoms persisted in 88, 86, and 48 percent of patients, respectively; at 15 months, 4 percent remained

symptomatic [58]. In contrast, among 88 patients in Reunion evaluated a mean of 18 months after confirmation of

acute chikungunya infection, 63 percent reported persistent polyarthralgia [60]. Morning stiffness was reported by 75

percent of individuals, and almost half reported that the pain had a negative impact on daily activities. Another study

of 180 patients from Reunion with viremic chikungunya infection found that at 36 months 60 percent still had

arthralgias [64]. One study in South Africa reported arthralgia three years after the acute illness in 12 percent of

patients [65].

Severe complications In older reports, chikungunya fever has been described as a self-limited illness, although

severe complications and death have been reported in the more recent outbreaks. It is unclear whether these

differences reflect a modulation in virus virulence, improved epidemiologic observation, or both. Severe

complications and death occur more often among patients older than 65 years and in those with underlying chronic

medical problems.

Severe complications include respiratory failure, cardiovascular decompensation, myocarditis, acute hepatitis, renal

failure, and neurologic involvement. Meningoencephalitis is the most common neurologic complication; other

manifestations include acute flaccid paralysis and Guillain Barr syndrome [66-68]. Ocular manifestations

(iridocyclitis, retinitis, episcleritis, macular choroiditis) and sensorineural hearing loss have also been described

[61,69,70]. In Reunion, the estimated incidence of severe disease (eg, hospitalized patients with complications, such

as respiratory failure, meningoencephalitis, acute hepatitis, or kidney failure) was 17 per 100,000 population [18,71].

Deaths associated with chikungunya virus infection were reported during outbreaks in Mauritius, Reunion, and India

[71-74]. In Reunion there were 228 deaths; the mean age was 78 years [71]. During the chikungunya epidemic in

Ahmedabad, India, in 2006, about 60,000 cases were described; the number of deaths during the four months of

peak epidemic activity exceeded the average death rate during those months in the previous four years by almost

3000 [74].

Subclinical infection Some individuals have serologic evidence for exposure to chikungunya virus infection in

the absence of clinical symptoms. As noted above, in West Africa seropositivity has been noted in 35 to 50 percent

of the individuals in the absence of recognized outbreaks. During the Reunion outbreak, a survey found that about

3.2 percent of military policemen were seropositive in the absence of clinical symptoms [75]. A Thai study noted a

ratio of clinical-to-subclinical chikungunya infection of about 1.8:1 [76].

DIFFERENTIAL DIAGNOSIS Prominent arthralgia, high fever, diffuse rash, and absence of respiratory symptoms

can help to distinguish chikungunya from other illnesses. The differential diagnosis includes:


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Dengue fever Dengue virus and chikungunya infections share some clinical symptoms and areas of

geographic distribution; distinguishing them may be difficult in the setting of acute febrile illness with rash.

However, polyarthralgia occurs in virtually all cases of chikungunya fever but is not typical of dengue fever [77].

Cytopenia, particularly thrombocytopenia, may distinguish dengue from chikungunya infection. The diagnosis is

established via serology. (See "Clinical manifestations and diagnosis of dengue virus infection".)

Seronegative rheumatoid arthritis Clinical manifestations of seronegative rheumatoid arthritis include

inflammatory arthritis involving three or more joints for >6 weeks, with negative rheumatoid factor and

anticyclic citrullinated peptide (CCP) antibody tests. It is a diagnosis of exclusion. (See "Diagnosis and

differential diagnosis of rheumatoid arthritis", section on 'Patients not meeting above criteria'.)

African tick bite fever African tick bite fever occurs as a result of infection with Rickettsia africae and is

observed among travelers to Africa [78]. It is associated with headache, fever, myalgia, solitary or multiple

eschars with regional lymphadenopathy, and generalized rash. The diagnosis is established via serology. (See

"Other spotted fever group rickettsial infections".)

Enteric fever Clinical manifestations of enteric fever include fever, bradycardia, abdominal pain, and,

infrequently, a rash (rose spots). The presentation of enteric fever is typically subacute, whereas the

presentation of chikungunya infection is typically abrupt in onset. The diagnosis is established by stool and/or

blood culture. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of typhoid fever".)

Leptospirosis Leptospirosis is characterized by fever, rigors, myalgia, and headache. Less common

symptoms include cough, nausea, vomiting, diarrhea, abdominal pain, and arthralgia. It may be distinguished

from chikungunya infection by the presence of conjunctival suffusion and jaundice. The diagnosis is established

via serology. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of leptospirosis".)

Malaria Malaria is characterized by fever, malaise, nausea, vomiting, abdominal pain, diarrhea, myalgia, and

anemia. Fever in the setting of malaria is often intermittent, whereas fever in the setting of chikungunya

infection is typically persistent. The diagnosis of malaria is established by visualization of parasites on

peripheral smear. (See "Clinical manifestations of malaria".)

Relapsing fever Clinical manifestations of relapsing fever include fever, headache, neck stiffness, arthralgia,

myalgia, and nausea. Fever in the setting of relapsing fever is typically intermittent, whereas fever in the setting

of chikungunya infection is typically persistent. Diagnostic tools include direct smear and polymerase chain

reaction (PCR). (See "Clinical features, diagnosis, and management of relapsing fever".)

Ross river virus Clinical manifestations of Ross River virus infection include fever, arthritis, and rash.

Epidemiologic history can help to exclude Ross River virus infection as it is transmitted only in Australia. The

diagnosis of Ross River virus is typically established by serology. (See "Ross River virus infection".)

Measles Clinical manifestations of measles include fever, cough, sore throat, coryza, conjunctivitis, and

lymphadenitis. Koplik spots may precede generalized rash. The diagnosis is established via serology. (See

"Clinical manifestations and diagnosis of measles".)

Rubella Clinical manifestations of rubella include low-grade fever, coryza, conjunctivitis, and

lymphadenopathy. Macular rash begins on the face and spreads to the trunk, and arthritis may be present. The

diagnosis is established via serology. (See "Rubella".)

Epstein-Barr virus Clinical manifestations of mononucleosis include fever, malaise, and pharyngitis.

Lymphadeonpathy and splenomegaly may be present along with atypical lymphocytosis. The diagnosis is

established via detection of heterophile antibodies.

Meningococcal infection Meningococcal infection may be associated with meningitis and hemorrhagic rash.

The diagnosis is established based on cerebrospinal fluid examination. (See "Clinical manifestations of

meningococcal infection".)


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Other infections in the differential diagnosis include primary HIV infection and rickettsial infections. The possibility of

dual infection should be considered if the clinical course is atypical or fever persists longer than five to seven days

[79]. Chikungunya virus outbreaks have occurred simultaneously with outbreaks of dengue, Zika virus [36], or yellow

fever [80], and coinfection with chikungunya virus and other pathogens has been described (eg, chikungunya and

dengue [81], chikungunya and yellow fever [79], chikungunya and amebiasis [82]).

DIAGNOSIS Diagnostic techniques for identification of chikungunya virus include serology, viral culture, and

molecular techniques [11,21,53]. Serology is the primary tool for diagnosis in the clinical setting. Immunoglobulin M

(IgM) anti-chikungunya virus antibodies (detected by direct enzyme-linked immunosorbent assay [ELISA]) are

present starting about five days (range 1 to 12 days) following onset of symptoms and persist for several weeks to

three months. Immunoglobulin G (IgG) antibodies begin to appear about two weeks following onset of symptoms

and persist for years.

In endemic areas, chikungunya infection can be suspected based on characteristic clinical findings in outbreaks; in

endemic areas where good laboratory facilities are unavailable, many infections may remain undiagnosed.

Viral culture and molecular techniques are important research tools. Chikungunya virus can be isolated from blood

during the first week of illness using mosquito cells, mammalian cells (Vero), or in mice. Sensitivity of viral culture is

high in early infection but drops five days after onset of illness. Chikungunya virus RNA can also be detected by

reverse transcription polymerase chain reaction (RT-PCR) during the first five days following onset of symptoms with

excellent sensitivity and specificity [11]. Virus isolation allows identification of the viral strain and can be important for

epidemiologic and research purposes, but RT-PCR is faster than culture with greater sensitivity and specificity.

TREATMENT AND PREVENTION Treatment of chikungunya infection consists of supportive care including

antiinflammatory agents that relieve symptoms in many patients and analgesic agents [58]. No antiviral agents have

been shown to be effective in human infection, although ribavirin and interferon-alpha appear to have in vitro activity

against virus replication [83]. Chloroquine sulfate has been suggested as a possible treatment because of its

antiinflammatory properties but has not been demonstrated to be effective [84]. For seriously ill patients, there are

insufficient data for use of corticosteroids or antiviral therapy. The documentation of long-term viral persistence in

nonhuman primates raises questions about the roles immune dysregulation and persistent virus in chronic

symptoms [85].

Thus far, there is no licensed vaccine for prevention of chikungunya infection; active research is under way to

develop a vaccine using variety of approaches [86-90]. Active work is also underway to develop monoclonal

antibodies for treatment [91].

Prevention consists of minimizing mosquito exposure [92]. Patients receiving care in an area inhabited by

mosquitoes competent to transmit chikungunya virus should be treated in screened, mosquito-free areas or under a

bednet to avoid spread. (See "Prevention of arthropod and insect bites: Repellents and other measures".)

SUMMARY AND RECOMMENDATIONS

Chikungunya is an arthropod-borne virus (arbovirus) endemic to West Africa that causes acute febrile

polyarthralgia and arthritis. (See 'Introduction' above.)

Chikungunya virus appears to spread across wide geographic areas via travel of infected individuals between

regions where competent mosquitoes exist for perpetuation of local transmission. Multiple outbreaks beyond

West Africa have been described; since 2004, chikungunya virus has spread broadly, causing massive

outbreaks with explosive onset in the Indian Ocean region, India, other parts of Asia, Europe, and, most

recently, the Americas. (See 'Epidemiology' above.)

Clinical manifestations of acute infection include high fever and bilateral polyarthralgia with intense pain. The

most common skin manifestation is macular or maculopapular rash (usually appearing three days or later after

onset of illness and lasting three to seven days). Additional manifestations may include headache, myalgia,

and gastrointestinal symptoms. (See 'Acute infection' above.)


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Many patients experience persistent rheumatologic symptoms following acute illness. These may include

polyarthralgia, morning stiffness, tenosynovitis, and Raynaud phenomena. Severe complications (including

meningoencephalitis, cardiopulmonary decompensation, acute renal failure, and death) have been described

with greater frequency among patients older than 65 years and those with underlying chronic medical

problems. (See 'Persistent symptoms' above and 'Severe complications' above.)

Serology is the primary tool for diagnosis in the clinical setting. Immunoglobulin M (IgM) anti-chikungunya virus

antibodies are present starting about five days (range 1 to 12 days) following onset of symptoms and persist for

several weeks to three months. Immunoglobulin G (IgG) antibodies start to appear about two weeks following

onset of symptoms and persist for years. (See 'Diagnosis' above.)

Treatment of chikungunya infection consists of supportive care including antiinflammatory and analgesic

agents. No antiviral agents have been shown to be effective in human infection. Prevention consists of

minimizing mosquito exposure. Patients receiving care in an area inhabited by mosquitoes competent to

transmit chikungunya should be treated in screened, mosquito-free areas or under a bednet to avoid spread.

(See 'Treatment and prevention' above.)


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Disclosures: Mary Elizabeth Wilson, MD Nothing to disclose. Martin S Hirsch, MD Nothing to disclose. Elinor L Baron, MD, DTMHNothing to disclose.

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Conflict of interest policy

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