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Chikungunya fever
Author
Mary Elizabeth Wilson, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Elinor L Baron, MD, DTMH
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 <40 years old versus 8.8 percent
for those 80 years of age and older) [24]. Cases of chikungunya fever related to local transmission ceased in Italy
when temperatures dropped, and human cases were not reported in 2008. Local transmission occurred in France in
2010 [25] and was subsequently reported again in 2014 [26].
Because the Indian Ocean islands, India, and Malaysia are popular tourist destinations among European travelers,
many imported cases of chikungunya fever appeared in Europe at the time of the outbreaks in India and the Indian
Ocean islands [27].
Americas In December 2013, chikungunya fever was reported in the Caribbean Island of Saint Martin [3,28].
Since then, local transmission has been confirmed in many countries and territories in the Caribbean, North
America, Central America, and South America [28-32]. The majority of cases reported in the continental United
States have been imported cases [29,30,33]. The first two cases of local transmission in the continental United
States were reported in Florida in mid-July 2014 [31,32,34]; local transmission has been reported more widely in
Puerto Rico [33,35]. This is the first time that local transmission of chikungunya virus has been reported in the
Americas.
The United States Centers for Disease Control maintains a page summarizing the status of chikungunya
transmission in the Caribbean and the Americas.
Pacific region In 2013 and 2014, outbreaks of chikungunya virus infection spread in the Pacific region on
multiple islands, including Tonga, American Samoa, Yap, Papua New Guinea, and others. Concurrent outbreaks of
dengue and Zika virus infection have been confirmed on some of the islands [36].
TRANSMISSION In endemic areas of Africa, chikungunya virus transmission occurs in a cycle involving humans,
several species of Aedes mosquitoes that inhabit forests and villages, and animals (nonhuman primates and
perhaps other animals). In Asia and elsewhere, however, major outbreaks are sustained by mosquito transmission
among susceptible humans. The virus can spread via travel of infected individuals between regions where
competent mosquitoes exist for perpetuation of local transmission. (See 'Epidemiology' above.)
Mosquito vectors The major chikungunya virus mosquito vectors are Aedes aegypti and Aedes albopictus.
These vectors are also capable of transmitting dengue virus, which, like chikungunya virus, is increasing in
geographic range and intensity of transmission. (See "Mosquito vectors of infectious diseases" and "Epidemiology of
dengue virus infections".)
Aedes aegypti Ae. aegypti is well adapted to urban settings and is widely distributed in urban areas of the
tropics and subtropics. It prefers the human host as a source of blood meals and breeds readily in flowerpots and in
trash, such as discarded cups. A single Ae. aegypti mosquito may be able to infect more than one human, since this
species feeds on another host if its blood meal is interrupted.
Ae. aegypti is found in the southeastern United States and in limited parts of the Southwest [31].
Aedes albopictus Ae. albopictus (the so-called Asian tiger mosquito) is competent to transmit a number of
arboviruses in the laboratory (including yellow fever, West Nile, Japanese encephalitis, and eastern equine
encephalitis viruses). It bites a range of animal species so has been considered a relatively inefficient vector, since
blood meals taken from nonsusceptible hosts do not contribute to virus transmission [37]. However, some
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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 109 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].
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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, interferongamma, 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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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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REFERENCES
1. Charrel RN, de Lamballerie X, Raoult D. Chikungunya outbreaks--the globalization of vectorborne diseases. N
Engl J Med 2007; 356:769.
2. Mavalankar D, Shastri P, Raman P. Chikungunya epidemic in India: a major public-health disaster. Lancet
Infect Dis 2007; 7:306.
3. Morens DM, Fauci AS. Chikungunya at the door--dj vu all over again? N Engl J Med 2014; 371:885.
4. Enserink M. Infectious diseases. Chikungunya: no longer a third world disease. Science 2007; 318:1860.
5. Pan American Health Organization. Preparedness and response for chikungunya virus: introduction into the
Americas. Washington, DC: PAHO; 2011. http://new.paho.org/hq/index.php?option=com_content&task=view&
id=6464&itemid=1926 (Accessed on October 05, 2012).
6. Chevillon C, Briant L, Renaud F, Devaux C. The Chikungunya threat: an ecological and evolutionary
perspective. Trends Microbiol 2008; 16:80.
7. Staples JE, Breiman RF, Powers AM. Chikungunya fever: an epidemiological review of a re-emerging
infectious disease. Clin Infect Dis 2009; 49:942.
8. Weaver SC, Lecuit M. Chikungunya virus and the global spread of a mosquito-borne disease. N Engl J Med
2015; 372:1231.
9. Parola P, de Lamballerie X, Jourdan J, et al. Novel chikungunya virus variant in travelers returning from Indian
Ocean islands. Emerg Infect Dis 2006; 12:1493.
10. Hochedez P, Jaureguiberry S, Debruyne M, et al. Chikungunya infection in travelers. Emerg Infect Dis 2006;
12:1565.
11. Panning M, Grywna K, van Esbroeck M, et al. Chikungunya fever in travelers returning to Europe from the
Indian Ocean region, 2006. Emerg Infect Dis 2008; 14:416.
12. Lanciotti RS, Kosoy OL, Laven JJ, et al. Chikungunya virus in US travelers returning from India, 2006. Emerg
Infect Dis 2007; 13:764.
13. Nicoletti L, Ciccozzi M, Marchi A, et al. Chikungunya and dengue viruses in travelers. Emerg Infect Dis 2008;
14:177.
14. Centers for Disease Control and Prevention (CDC). Chikungunya fever diagnosed among international
travelers--United States, 2005-2006. MMWR Morb Mortal Wkly Rep 2006; 55:1040.
15. Centers for Disease Control and Prevention (CDC). Update: chikungunya fever diagnosed among international
travelers--United States, 2006. MMWR Morb Mortal Wkly Rep 2007; 56:276.
Chikungunya fever
9 de 12
http://www.uptodate.com.wdg.biblio.udg.mx:2048/contents/chikungunya...
16. Gibney KB, Fischer M, Prince HE, et al. Chikungunya fever in the United States: a fifteen year review of cases.
Clin Infect Dis 2011; 52:e121.
17. Sergon K, Njuguna C, Kalani R, et al. Seroprevalence of Chikungunya virus (CHIKV) infection on Lamu Island,
Kenya, October 2004. Am J Trop Med Hyg 2008; 78:333.
18. Renault P, Solet JL, Sissoko D, et al. A major epidemic of chikungunya virus infection on Reunion Island,
France, 2005-2006. Am J Trop Med Hyg 2007; 77:727.
19. Sissoko D, Malvy D, Giry C, et al. Outbreak of Chikungunya fever in Mayotte, Comoros archipelago,
2005-2006. Trans R Soc Trop Med Hyg 2008; 102:780.
20. Yergolkar PN, Tandale BV, Arankalle VA, et al. Chikungunya outbreaks caused by African genotype, India.
Emerg Infect Dis 2006; 12:1580.
21. Lakshmi V, Neeraja M, Subbalaxmi MV, et al. Clinical features and molecular diagnosis of Chikungunya fever
from South India. Clin Infect Dis 2008; 46:1436.
22. AbuBakar S, Sam IC, Wong PF, et al. Reemergence of endemic Chikungunya, Malaysia. Emerg Infect Dis
2007; 13:147.
23. Wu D, Wu J, Zhang Q, et al. Chikungunya outbreak in Guangdong Province, China, 2010. Emerg Infect Dis
2012; 18:493.
24. Rezza G, Nicoletti L, Angelini R, et al. Infection with chikungunya virus in Italy: an outbreak in a temperate
region. Lancet 2007; 370:1840.
25. Gould EA, Gallian P, De Lamballerie X, Charrel RN. First cases of autochthonous dengue fever and
chikungunya fever in France: from bad dream to reality! Clin Microbiol Infect 2010; 16:1702.
26. World Health Organization. Global Alert and Response: Chikungunya - France. http://www.who.int/csr/don
/23-october-2014-chikungunya/en/ (Accessed on October 23, 2014).
27. Pialoux G, Gazre BA, Jaurguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis
2007; 7:319.
28. Centers for Disease Control and Prevention. Chikungunya in the Caribbean. http://wwwnc.cdc.gov/travel
/notices/watch/chikungunya-saint-martin (Accessed on June 02, 2014).
29. Pan American Health Organization, World Health Organization. Chikungunya. http://www.paho.org
/hq/index.php?option=com_content&view=article&id=9053&Itemid=39843 (Accessed on July 21, 2014).
30. Fischer M, Staples JE, Arboviral Diseases Branch, National Center for Emerging and Zoonotic Infectious
Diseases, CDC. Notes from the field: chikungunya virus spreads in the Americas - Caribbean and South
America, 2013-2014. MMWR Morb Mortal Wkly Rep 2014; 63:500.
31. Centers for Disease Control and Prevention. CDC newsroom - press release. First Chikungunya case acquired
in the United States reported in Florida. http://www.cdc.gov/media/releases/2014/p0717-chikungunya.html
(Accessed on July 18, 2014).
32. Florida Health. Florida Department of Health confirms first locally acquired cases of chikungunya fever.
http://newsroom.doh.state.fl.us/wp-content/uploads/newsroom/2014/05/071714-Locally-AquiredChikungunya.pdf (Accessed on July 18, 2014).
33. Centers for Disease Control and Prevention. Chikungunya virus in the United States. http://www.cdc.gov
/chikungunya/geo/united-states.html (Accessed on July 18, 2014).
34. Kendrick K, Stanek D, Blackmore C, Centers for Disease Control and Prevention (CDC). Notes from the field:
Transmission of chikungunya virus in the continental United States--Florida, 2014. MMWR Morb Mortal Wkly
Rep 2014; 63:1137.
35. Sharp TM, Roth NM, Torres J, et al. Chikungunya cases identified through passive surveillance and household
investigations--Puerto Rico, May 5-August 12, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:1121.
36. Roth A, Mercier A, Lepers C, et al. Concurrent outbreaks of dengue, chikungunya and Zika virus infections an unprecedented epidemic wave of mosquito-borne viruses in the Pacific 2012-2014. Euro Surveill 2014; 19.
37. Reiter P, Fontenille D, Paupy C. Aedes albopictus as an epidemic vector of chikungunya virus: another
emerging problem? Lancet Infect Dis 2006; 6:463.
38. Enserink M. Entomology. A mosquito goes global. Science 2008; 320:864.
Chikungunya fever
10 de 12
http://www.uptodate.com.wdg.biblio.udg.mx:2048/contents/chikungunya...
39. Rochlin I, Ninivaggi DV, Hutchinson ML, Farajollahi A. Climate change and range expansion of the Asian tiger
mosquito (Aedes albopictus) in Northeastern USA: implications for public health practitioners. PLoS One 2013;
8:e60874.
40. Gubler DJ. Aedes albopictus in Africa. Lancet Infect Dis 2003; 3:751.
41. Tatem AJ, Hay SI, Rogers DJ. Global traffic and disease vector dispersal. Proc Natl Acad Sci U S A 2006;
103:6242.
42. Caron M, Paupy C, Grard G, et al. Recent introduction and rapid dissemination of Chikungunya virus and
Dengue virus serotype 2 associated with human and mosquito coinfections in Gabon, central Africa. Clin Infect
Dis 2012; 55:e45.
43. Tesh RB, Gubler DJ, Rosen L. Variation among goegraphic strains of Aedes albopictus in susceptibility to
infection with chikungunya virus. Am J Trop Med Hyg 1976; 25:326.
44. Reiskind MH, Pesko K, Westbrook CJ, Mores CN. Susceptibility of Florida mosquitoes to infection with
chikungunya virus. Am J Trop Med Hyg 2008; 78:422.
45. Vazeille M, Jeannin C, Martin E, et al. Chikungunya: a risk for Mediterranean countries? Acta Trop 2008;
105:200.
46. Charrel RN, de Lamballerie X, Raoult D. Seasonality of mosquitoes and chikungunya in Italy. Lancet Infect Dis
2008; 8:5.
47. Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S. A single mutation in chikungunya virus affects vector
specificity and epidemic potential. PLoS Pathog 2007; 3:e201.
48. Brouard C, Bernillon P, Quatresous I, et al. Estimated risk of Chikungunya viremic blood donation during an
epidemic on Reunion Island in the Indian Ocean, 2005 to 2007. Transfusion 2008; 48:1333.
49. Couderc T, Gangneux N, Chrtien F, et al. Chikungunya virus infection of corneal grafts. J Infect Dis 2012;
206:851.
50. Grardin P, Barau G, Michault A, et al. Multidisciplinary prospective study of mother-to-child chikungunya virus
infections on the island of La Runion. PLoS Med 2008; 5:e60.
51. Ramful D, Sampriz S, Fritel X, et al. Antibody kinetics in infants exposed to Chikungunya virus infection
during pregnancy reveals absence of congenital infection. J Infect Dis 2014; 209:1726.
52. LUMSDEN WH. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. II.
General description and epidemiology. Trans R Soc Trop Med Hyg 1955; 49:33.
53. Simon F, Savini H, Parola P. Chikungunya: a paradigm of emergence and globalization of vector-borne
diseases. Med Clin North Am 2008; 92:1323.
54. Lidbury BA, Rulli NE, Suhrbier A, et al. Macrophage-derived proinflammatory factors contribute to the
development of arthritis and myositis after infection with an arthrogenic alphavirus. J Infect Dis 2008;
197:1585.
55. Schuffenecker I, Iteman I, Michault A, et al. Genome microevolution of chikungunya viruses causing the Indian
Ocean outbreak. PLoS Med 2006; 3:e263.
56. Bordi L, Carletti F, Castilletti C, et al. Presence of the A226V mutation in autochthonous and imported Italian
chikungunya virus strains. Clin Infect Dis 2008; 47:428.
57. Burt FJ, Rolph MS, Rulli NE, et al. Chikungunya: a re-emerging virus. Lancet 2012; 379:662.
58. Simon F, Parola P, Grandadam M, et al. Chikungunya infection: an emerging rheumatism among travelers
returned from Indian Ocean islands. Report of 47 cases. Medicine (Baltimore) 2007; 86:123.
59. Taubitz W, Cramer JP, Kapaun A, et al. Chikungunya fever in travelers: clinical presentation and course. Clin
Infect Dis 2007; 45:e1.
60. Borgherini G, Poubeau P, Staikowsky F, et al. Outbreak of chikungunya on Reunion Island: early clinical and
laboratory features in 157 adult patients. Clin Infect Dis 2007; 44:1401.
61. Mahendradas P, Ranganna SK, Shetty R, et al. Ocular manifestations associated with chikungunya.
Ophthalmology 2008; 115:287.
62. Parola P, Simon F, Oliver M. Tenosynovitis and vascular disorders associated with Chikungunya virus-related
Chikungunya fever
11 de 12
http://www.uptodate.com.wdg.biblio.udg.mx:2048/contents/chikungunya...
Chikungunya fever
12 de 12
http://www.uptodate.com.wdg.biblio.udg.mx:2048/contents/chikungunya...
87. Akahata W, Yang ZY, Andersen H, et al. A virus-like particle vaccine for epidemic Chikungunya virus protects
nonhuman primates against infection. Nat Med 2010; 16:334.
88. Roy CJ, Adams AP, Wang E, et al. Chikungunya vaccine candidate is highly attenuated and protects
nonhuman primates against telemetrically monitored disease following a single dose. J Infect Dis 2014;
209:1891.
89. Chang LJ, Dowd KA, Mendoza FH, et al. Safety and tolerability of chikungunya virus-like particle vaccine in
healthy adults: a phase 1 dose-escalation trial. Lancet 2014; 384:2046.
90. Ramsauer K, Schwameis M, Firbas C, et al. Immunogenicity, safety, and tolerability of a recombinant measlesvirus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, firstin-man trial. Lancet Infect Dis 2015; 15:519.
91. Fric J, Bertin-Maghit S, Wang CI, et al. Use of human monoclonal antibodies to treat Chikungunya virus
infection. J Infect Dis 2013; 207:319.
92. Centers for Disease Control and Prevention. Health Information for International Travel, Oxford University
Press, New York 2014.
Topic 3024 Version 42.0
Disclosures
Disclosures: Mary Elizabeth Wilson, MD Nothing to disclose. Martin S Hirsch, MD Nothing to disclose. Elinor L Baron, MD, DTMH
Nothing to disclose.
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