The best means of prevention is overall mosquito control and the avoidance of bites by any infected

mosquitoes.[8] No specific treatment is known, but medications can be used to reduce symptoms. [8] Rest and
fluids may also be useful.[9]
Contents
[hide]

1 Signs and symptoms

1.1 Chronic disease

2 Virology
2.1 Type-1 interferon

3 Diagnosis
3.1 Differential diagnosis

4 Prevention
4.1 Vaccine

5 Treatment
5.1 Chronic arthritis

6 Epidemiology

7 History

8 Society and culture

o

8.1 Biological weapon

9 References

10 Further reading

11 External links

Signs and symptoms[edit]

The incubation period of chikungunya disease ranges from 2 to 12 days, typically two to three. The majority of
those infected will develop symptoms.[10] Symptoms include a fever up to 40 C
(104 F), petechial or maculopapular rash of the trunk and occasionally the limbs, and arthralgia or arthritis
affecting multiple joints.[11] Othernonspecific symptoms can include headache, nausea, vomiting, conjunctivitis,
slight photophobia, and partial loss of taste.[12] Ocular inflammation from chikungunya may present

as iridocyclitis, or uveitis. Retinal lesions may also occur.[13] Swelling of legs is observed in many people, the
cause of which remains obscure as it is not related to any cardiovascular, renal, or hepatic abnormalities.
Typically, the fever lasts for two days and then ends abruptly. However, other symptoms, namely joint pain,
intense headache, insomnia and an extreme degree of prostration, last for a variable period, usually about five
to seven days.[11] People have complained of joint pains for much longer time periods, some as long as two
years, depending on their age.[14][15] Recovery from the disease varies by age. Younger people recover within five
to 15 days; middle-aged people recover in 1.0 to 2.5 months. Recovery is longer for the elderly. The severity of
the disease, as well as its duration, is less in younger people and pregnant women. In pregnant women, no
untoward effects are noticed after the infection.

Chronic disease[edit]
Observations during recent epidemics have suggested chikungunya may cause long-term symptoms following
acute infection. During the La Reunion outbreak in 2006, more than 50% of subjects over the age of 45
reported long-term musculoskeletal pain[16] with up to 60% of people reporting prolonged arthralgia three years
following initial infection.[17] A study of imported cases in France reported that 59% of people still suffered from
arthralgia two years after acute infection.[18] Following a local epidemic of chikungunya in Italy, 66% of people
reported muscles pains, joint pains, or asthenia at one year after acute infection. [19] Long-term symptoms are
not an entirely new observation; long-term arthritis was observed following an outbreak in 1979. [20] Common
predictors of prolonged symptoms are increased age and prior rheumatological disease. [16][17][19][21] The cause of
these chronic symptoms is currently not fully known. Markers of autoimmune or rheumatoid disease have not
been found in people reporting chronic symptoms. [17][22] However, some evidence from humans and animal
models suggests chikungunya may be able to establish chronic infections within the host. Viral antigen was
detected in a muscle biopsy of a people suffering a recurrent episode of disease three months after initial
onset.[23]Additionally, viral antigen and RNA were found in synovial macrophages of a person during a relapse of
musculoskeletal disease 18 months after initial infection.[24]Several animal models have also suggested
chikungunya virus may establish persistent infections. In a mouse model, viral RNA was detected specifically in
joint-associated tissue for at least 16 weeks after inoculation, and was associated with chronic synovitis.
[25]

Similarly, another study reported detection of a viral reporter gene in joint tissue of mice for weeks after

inoculation.[26] In a nonhuman primate model, chikungunya virus was found to persist in the spleen for at least
six weeks.[27]

Virology[edit]
Chikungunya virus

Cryoelectron microscopy reconstruction

of chikungunya virus.
From EMDB entryEMD-5577[28]

Virus classification

Group:

Group IV ((+)ssRNA)

Order:

Unassigned

Family:

Togaviridae

Genus:

Alphavirus

Species:

Chikungunya virus

Chikungunya virus is an alphavirus with a positive-sense single-stranded RNA genome of about 11.6kb. It is a
member of theSemliki Forest virus complex and is closely related to Ross River virus, O'nyong'nyong virus,
and Semliki Forest virus.[29] In the United States, it is classified as a category C priority pathogen [30] and work
requires biosafety level III precautions.[31]
Human epithelial and endothelial cells, primary fibroblasts, and monocyte-derived macrophages are permissive
for chikungunya virus in vitro, and viral replication is highly cytopathic, but susceptible to type-I and -II
interferon.[32] In vivo, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells, and
myofibers.[23][33][34]
Chikungunya virus is an alphavirus and the viruses that cause eastern equine encephalitis and western equine
encephalitis.[35]

Chikungunya is generally spread through bites from A. aegypti mosquitoes, but recent research by the Pasteur
Institute in Paris has suggested chikungunya virus strains in the 2005-2006 Reunion Island outbreak incurred a
mutation that facilitated transmission by the Asian tiger mosquito (A. albopictus).[36]
Chikungunya virus infection of A. albopictus was caused by a point mutation in one of the viral envelope genes
(E1).[37][38]Enhanced transmission of chikungunya virus by A. albopictus could mean an increased risk for
outbreaks in other areas where the Asian tiger mosquito is present. A recent epidemic in Italy was likely
perpetuated by A. albopictus.[39] In Africa, chikungunya is spread by a sylvatic cycle in which the virus largely
resides in other primates between human outbreaks.[35]

Type-1 interferon[edit]
Upon infection with chikungunya, the host's fibroblasts produce type-1 (alpha and beta) interferon.[40] Mice that
lack the interferon alpha receptor die in two to three days upon being exposed to 10 2 chikungunya PFUs, while
wild-type mice survive even when exposed to as many as 10 6 PFUs of the virus.[40] At the same time, mice that
are partially type-1 deficient (IFN / +/) are mildly affected and experience symptoms such as muscle
weakness and lethargy.[41] Partidos et al. 2011 saw similar results with the live attenuated strain CHIKV181/25.
However, rather than dying, the type-1 interferon-deficient (IFN / /) mice were temporarily disabled and the
partially type-1 interferon-deficient mice did not have any problems. [42]
Several studies have attempted to find the upstream components of the type-1 interferon pathway involved in
the host's response to chikungunya infection. So far, no one knows the chikungunya-specific pathogen
associated molecular pattern.[43] Nonetheless, IPS-1also known as Cardif, MAVS, and VISAhas been found
to be an important factor. In 2011, White et al. found that interfering with IPS-1 decreased the phosphorylation
of interferon regulatory factor 3 (IRF3) and the production of IFN-.[43] Other studies have found that IRF3
and IRF7 are important in an age-dependent manner. Adult mice that lack both of these regulatory factors die
upon infection with chikungunya.[44] Neonates, on the other hand, succumb to the virus if they are deficient in
one of these factors.[45]
Chikungunya counters the type-I interferon response by producing NS2, a nonstructural protein that degrades
Rpb and turns off the host cell's ability to transcribe DNA. [46] NS2 interferes with the JAK-STAT signaling
pathway and prevents STAT from becoming phosphorylated. [47]

Diagnosis[edit]
Common laboratory tests for chikungunya include RT-PCR, virus isolation, and serological tests.

Virus isolation provides the most definitive diagnosis, but takes one to two weeks for completion and
must be carried out in biosafety level III laboratories.[48] The technique involves exposing specific cell
lines to samples from whole blood and identifying chikungunya virus-specific responses.

RT-PCR using nested primer pairs is used to amplify several chikungunya-specific genes from whole
blood. Results can be determined in one to two days.[48]

Serological diagnosis requires a larger amount of blood than the other methods, and uses
an ELISA assay to measure chikungunya-specific IgM levels. Results require two to three days, and false

positives can occur with infection via other related viruses, such as o'nyong'nyong virus and Semliki Forest
virus.[48]

Differential diagnosis[edit]
The differential diagnosis may include infection with other mosquito-borne viruses, such as dengue and
influenza. Chronic recurrent polyarthralgia occurs in at least 20% of chikungunya patients one year after
infection, whereas such symptoms are uncommon in dengue. [49]

Prevention[edit]

An A. aegypti mosquito biting a person

The most effective means of prevention are protection against contact with the disease-carrying mosquitoes
and mosquito control.[8] These include using insect repellents with substances such as DEET (N,N-diethylmeta-toluamide; also known as N,N'-diethyl-3-methylbenzamide or NNDB), icaridin (also known as picaridin
and KBR3023), PMD (p-menthane-3,8-diol, a substance derived from the lemon eucalyptus tree), or IR3535.
Wearing bite-proof long sleeves and trousers also offers protection.
In addition, garments can be treated with pyrethroids, a class of insecticides that often has repellent properties.
Vaporized pyrethroids (for example in mosquito coils) are also insect repellents. Securing screens on windows
and doors will help to keep mosquitoes out of the house. In the case of the day-active A. aegypti and A.
albopictus, however, this will have only a limited effect, since many contacts between the mosquitoes and
humans occur outside.

Vaccine[edit]
Currently, no approved vaccines are available. A phase-II vaccine trial used a live, attenuated virus, to develop
viral resistance in 98% of those tested after 28 days and 85% still showed resistance after one year.
[50]

However, 8% of people reported transient joint pain, and attenuation was found to be due to only two

mutations in the E2 glycoprotein.[51] Alternative vaccine strategies have been developed, and show efficacy in
mouse models, but have so far not reached clinical trials. [52][53] In August 2014 it was revealed researchers at
the National Institute of Allergy and Infectious Diseases were testing an experimental vaccine.[54] If a vaccine
becomes available, public health officials will then have to decide who should be vaccinated and under what
conditions a vaccination is necessary. Chikungunya will be difficult to control with a vaccine alone. [55]

Treatment[edit]

Currently, no specific treatment is available.[8] Attempts to relieve the symptoms include the use of NSAIDs such
as naproxen or paracetamol (acetaminophen) and fluids.[8] Aspirin is not recommended.[56]

Chronic arthritis[edit]
In those who have more than two weeks of arthritis, ribavirin may be useful.[8] The effect of chloroquine is not
clear.[8] It does not appear to help acute disease, but tentative evidence indicates it might help those with
chronic arthritis.[8] Steroids do not appear useful, either.[8]

Epidemiology[edit]
Main article: Chikungunya outbreaks

Cases of chikungunya fever (between 1952 and 2006) have been reported in the countries depicted in red on this map: Since 2006,
local transmission has occurred in areas within Taiwan, Australia, the Caribbean, Venezuela, and the United States.

Three genotypes of this virus have been described: West African, East/Central/South African, and Asian
genotypes.[57]Explosive epidemics in Indian Ocean in 2005 and Pacific Islands in 2011, as well as now in the
Americas, continue to change the distribution of genotypes, like the 5 serotypes of dengue, an entry of a new
genotype into a previously infected area causes new epidemics. [58]
On 28 May 2009 in Changwat Trang of Thailand, where the virus is endemic, the provincial hospital decided to
deliver byCaesarean section a male baby from his chikungunya-infected mother, Khwanruethai Sutmueang, 28,
a Trang native, to prevent mother-fetus virus transmission. However, after delivering the baby, the physicians
discovered the baby was already infected with the virus, and put him into intensive care because the infection
had left the baby unable to breathe by himself or to drink milk. The physicians presumed the virus might be
able to be transmitted from a mother to her fetus, but without laboratory confirmation. [59]
In December 2013, chikungunya was confirmed on the Caribbean island of St. Martin with 66 confirmed cases
and suspected cases of around 181.[60] This outbreak is the first time in the Western Hemisphere that the
disease has spread to humans from a population of infected mosquitoes. [61] By January 2014, the Public Health
Agency of Canada reported that cases were confirmed on the British Virgin Islands, SaintBarthlemy, Guadeloupe, and Martinique.[62] In April 2014, chikungunya was also confirmed in the Dominican
Republic by the Centers for Disease Control and Prevention (CDC).[63] By the end of April, it had spread to 14
countries in all, including Jamaica, St. Lucia, and Haiti where an epidemic was declared.[64][65]

By the end of May 2014, over ten imported cases of the virus had been reported in the United States by people
traveling to Florida from areas where the virus is endemic. [66]
On June 2014 six cases of the virus were confirmed in Brazil, two in the city of Campinas in the state of So
Paulo. The six cases are Brazilian army soldiers who had recently returned from Haiti, where they were
participating in the reconstruction efforts.United Nations Stabilisation Mission in Haiti.[67] The information was
officially released by Campinas municipality health secretary that has taken the appropriate actions. [68]
On June 11, 2014, a case was reported in Forsyth County, North Carolina, USA.[69]
On June 16, 2014, Florida had a cumulative 42 cases. [70]
As of September 11, 2014, the number of reported cases in Puerto Rico for the year is at
1,636.http://www.elnuevodia.com/seextiendeelcontagiodelchikungunyaporlaisla-1851846.html
On June 17, 2014, Department of Health officials in the U.S. state of Mississippi confirmed they are
investigating the first potential case in a Mississippi resident who recently travelled to Haiti. [71]
On June 19, 2014, the virus had spread to Georgia, USA. [72]
On June 24, 2014, a case was reported in Poinciana, Polk County, Florida, USA.[70]
On June 25, 2014, the Health Department of the U.S. state of Arkansas confirmed one person from the Natural
State is carrying Chikungunya.[73]
On June 26, 2014, a case was reported in the Mexican state of Jalisco.[74]
On July 17, 2014, the first chikungunya case acquired in the United States were reported in Florida by
the Centers for Disease Control and Prevention.[75] Since 2006 over 200 cases have been reported in the United
States but only in people who had traveled to other countries. This is the first time the virus was passed by
mosquitoes to a person on the U.S. mainland.[76]
On September 2, 2014, the Centers for Disease Control and Prevention reported that there had been 7
confirmed cases of Chikungunya in the United States in people who had acquired the disease locally.[77]
On September 25, 2014, official authorities in El Salvador report over 30,000 confirmed cases of this new
epidemy. [78][79] The new epidemy is also on the raise in Jamaica.[80][81] Tourists to those countries are bearing the
risk to bring the virus to their own countries.
Chikungunya cases development in Western Hemisphere from 2013

Source:[60][82][83][84][85]

History[edit]
The word 'chikungunya' is thought to derive from a description in the Makonde language, meaning "that
which bends up", of the contorted posture of people affected with the severe joint pain
and arthritic symptoms associated with this disease.[86] The disease was first described by Marion
Robinson[87] and W.H.R. Lumsden[88] in 1955, following an outbreak in 1952 on the Makonde Plateau, along
the border between Mozambique and Tanganyika (the mainland part of modern day Tanzania).
According to the initial 1955 report about the epidemiology of the disease, the term 'chikungunya' is
derived from the Makonde root verb kungunyala, meaning to dry up or become contorted. In concurrent
research, Robinson glossed the Makonde term more specifically as "that which bends up". Subsequent
authors apparently overlooked the references to the Makonde language and assumed the term derived
from Swahili, the lingua franca of the region. The erroneous attribution of the term as a Swahili word has
been repeated in numerous print sources. Many erroneous spellings of the name of the disease are in
common use.
Since its discovery in Tanganyika, Africa, in 1952, chikungunya virus outbreaks have occurred occasionally
in Africa, South Asia, and Southeast Asia, but recent outbreaks have spread the disease over a wider
range.
The first recorded outbreak of this disease may have been in 1779. [89] This is in agreement with the
molecular genetics evidence that suggests it evolved around the year 1700. [90]

Society and culture[edit]

Biological weapon[edit]
Chikungunya was one of more than a dozen agents researched as potential biological weapons.[91]

References[edit]
1.

Jump up^ Powers AM, Logue CH (September 2007). "Changing patterns of chikungunya virus: reemergence of a zoonotic arbovirus". J. Gen. Virol. 88 (Pt 9): 236377.doi:10.1099/vir.0.828580. PMID 17698645.

2.

Jump up^ Sourisseau M, Schilte C, Casartelli N, et al. (June 2007). "Characterization of

reemerging chikungunya virus". PLoS Pathog. 3 (6):
e89.doi:10.1371/journal.ppat.0030089. PMC 1904475. PMID 17604450.

3.

Jump up^ Lahariya C, Pradhan SK (December 2006). "Emergence of chikungunya virus in Indian
subcontinent after 32 years: A review". J Vector Borne Dis 43 (4): 15160.PMID 17175699.