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Chikungunya is an infection caused by the ''Chikungunya virus'' (CHIKV). Symptoms include fever and
joint pains Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...
. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a rash. Symptoms usually improve within a week; however, occasionally the joint pain may last for months or years. The risk of death is around 1 in 1,000. The very young, old, and those with other health problems are at risk of more severe disease. The virus is spread between people by two types of mosquitos: ''
Aedes albopictus ''Aedes albopictus'' (''Stegomyia albopicta''), from the mosquito (Culicidae) family, also known as the (Asian) tiger mosquito or forest mosquito, is a mosquito native to the tropical and subtropical areas of Southeast Asia. In the past few cen ...
'' and ''
Aedes aegypti ''Aedes aegypti'', the yellow fever mosquito, is a mosquito that can spread dengue fever, chikungunya, Zika fever, Mayaro and yellow fever viruses, and other disease agents. The mosquito can be recognized by black and white markings on its l ...
''. They mainly bite during the day. The virus may circulate within a number of animals including birds and rodents. Diagnosis is by either testing the blood for the virus's RNA or
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
to the virus. The symptoms can be mistaken for those of
dengue fever Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic ...
and
Zika fever Zika fever, also known as Zika virus disease or simply Zika, is an infectious disease caused by the Zika virus. Most cases have no symptoms, but when present they are usually mild and can resemble dengue fever. Symptoms may include fever, red ...
. It is believed most people become immune after a single infection. The best means of prevention is overall mosquito control and the avoidance of bites in areas where the disease is common. This may be partly achieved by decreasing mosquito access to water and with the use of
insect repellent An insect repellent (also commonly called "bug spray") is a substance applied to skin, clothing, or other surfaces to discourage insects (and arthropods in general) from landing or climbing on that surface. Insect repellents help prevent and cont ...
and
mosquito nets A mosquito net is a type of meshed curtain that is circumferentially draped over a bed or a sleeping area, to offer the sleeper barrier protection against bites and stings from mosquitos, flies, and other pest insects, and thus against the d ...
. There is no vaccine and no specific treatment as of 2016. Recommendations include rest, fluids, and medications to help with fever and joint pain. While the disease typically occurs in Africa and Asia,
outbreak In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
s have been reported in Europe and the
Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. Along with t ...
since the 2000s. In 2014 more than a million suspected cases occurred. In 2014 it was occurring in Florida in the continental United States but as of 2016 there were no further locally acquired cases. The disease was first identified in 1952 in Tanzania. The term is from the
Kimakonde language Makonde, or Kimakonde, is the language spoken by the Makonde, an ethnic group in southeast Tanzania and northern Mozambique. Makonde is a central Bantu language closely related to Yao. The Matambwe (Matembwe) and Mabiha (Maviha) dialects are ...
and means "to become contorted".


Signs and symptoms

Around 85% of people infected with Chikungunya virus experience symptoms, typically beginning with a sudden high fever above . The fever is soon followed by severe muscle and joint pain. Pain usually affects multiple joints in the arms and legs, and is symmetric – i.e. if one elbow is affected, the other is as well. People with Chikungunya also frequently experience headache, back pain, nausea, and fatigue. Around half of those affected develop a rash, with reddening and sometimes small bumps on the palms, foot soles, torso, and face. For some, the rash remains constrained to a small part of the body; for others, the rash can be extensive, covering more than 90% of the skin. Some people experience gastrointestinal issues, with abdominal pain and vomiting. Others experience eye problems, namely sensitivity to light,
conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The ...
, and pain behind the eye. This first set of symptoms – called the "acute phase" of Chikungunya – lasts around a week, after which most symptoms resolve on their own. Many people continue to have symptoms after the "acute phase" resolves, termed the "post-acute phase" for symptoms lasting three weeks to three months, and the "chronic stage" for symptoms lasting longer than three months. In both cases, the lasting symptoms tend to be joint pains:
arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some ...
,
tenosynovitis Tenosynovitis is the inflammation of the fluid-filled sheath (called the synovium) that surrounds a tendon, typically leading to joint pain, swelling, and stiffness. Tenosynovitis can be either infectious or noninfectious. Common clinical manifes ...
, and/or
bursitis Bursitis is the inflammation of one or more bursae (fluid filled sacs) of synovial fluid in the body. They are lined with a synovial membrane that secretes a lubricating synovial fluid. There are more than 150 bursae in the human body. The bursae ...
. If the affected person had pre-existing joint issues, these tend to worsen. Overuse of a joint can result in painful swelling, stiffness, nerve damage, and neuropathic pain. Typically the joint pain improves with time; however, the chronic stage can last anywhere from a few months to several years. Joint pain is reported in 87–98% of cases, and nearly always occurs in more than one joint, though joint swelling is uncommon. Typically the affected joints are located in both arms and legs. Joints are more likely to be affected if they have previously been damaged by disorders such as
arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some ...
. Pain most commonly occurs in peripheral joints, such as the wrists, ankles, and joints of the hands and feet as well as some of the larger joints, typically the shoulders, elbows and knees. Pain may also occur in the muscles or ligaments. In more than half of cases, normal activity is limited by significant fatigue and pain. Infrequently, inflammation of the eyes may occur in the form of
iridocyclitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...
, or uveitis, and retinal lesions may occur. Temporary damage to the liver may occur. People with Chikungunya occasionally develop neurologic disorders, most frequently swelling or degeneration of the brain, inflammation or degneration of the myelin sheaths around neurons, Guillain–Barré syndrome,
acute disseminated encephalomyelitis Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord ...
,
hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...
(in newborns), and issues with visual processing. In particularly rare cases, people may develop behavioral changes, seizures, irritation of the
cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebe ...
or
meninges In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in ...
,
oculomotor nerve palsy Oculomotor nerve palsy or oculomotor neuropathy is an eye condition resulting from damage to the third cranial nerve or a branch thereof. As the name suggests, the oculomotor nerve supplies the majority of the muscles controlling eye movements (fou ...
, or paralysis of the eye muscles. Newborns are susceptible to particularly severe effects of Chikungunya infection. Signs of infection typically begin with fever, rash, and swelling at the extremities. Around half of newborns have a mild case of the disease that resolves on its own; the other half have severe disease with inflammation of the brain and
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s. In severe cases, affected newborns may also have issues with bleeding and bloodflow, and problems with heart function. In addition to newborns, the elderly, and those with diabetes,
heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
, liver and kidney diseases, and human immunodeficiency virus infection tend to have more severe cases of Chikungunya. Around 1 to 5 in 1,000 people with symptomatic Chikungunya die of the disease.


Cause


Virology

''Chikungunya virus'' (CHIKV), is a member of the genus ''
Alphavirus ''Alphavirus'' is a genus of RNA viruses, the sole genus in the ''Togaviridae'' family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphaviruses, w ...
'', and family ''
Togaviridae This category is for articles about virus families (or redirects to such articles). There should be no subcategories. families Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity ( ...
''. It was first isolated in 1953 in Tanzania and is an RNA virus with a positive-sense single-stranded genome of about 11.6kb. It is a member of the Semliki Forest virus complex and is closely related to
Ross River virus ''Ross River virus'' (RRV) is a small encapsulated single-strand RNA '' Alphavirus'' endemic to Australia, Papua New Guinea and other islands in the South Pacific. It is responsible for a type of mosquito-borne non-lethal but extremely debilit ...
,
O'nyong'nyong virus The o'nyong'nyong virus (ONNV) was first isolated by researchers at the Uganda Virus Research Institute in Entebbe, Uganda, during a large outbreak of a disease in 1959 that resembled dengue fever. ONNV is a togavirus (family Togaviridae), genu ...
, and
Semliki Forest virus The Semliki Forest virus is an alphavirus found in central, eastern, and southern Africa. It was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942 and described by Smithburn and Haddow. ...
. Because it is transmitted by
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chitin, o ...
s, namely mosquitoes, it can also be referred to as an
arbovirus Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term ''arbovirus'' is a portmanteau word (''ar''thropod-''bo''rne ''virus''). ''Tibovirus'' (''ti''ck-''bo''rne ''virus'') is sometimes used to more spe ...
(''ar''thropod-''bo''rne virus). In the United States, it is classified as a category B priority pathogen, and work requires biosafety level III precautions.


Transmission

Chikungunya is generally transmitted from mosquitoes to humans. Less common modes of transmission include vertical transmission, which is transmission from mother to child during pregnancy or at birth. Transmission via infected blood products and through organ donation is also theoretically possible during times of outbreak, though no cases have yet been documented. The
incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the in ...
ranges from one to twelve days, and is most typically three to seven. Chikungunya is related to mosquitoes, their environments, and human behavior. The adaptation of mosquitoes to the changing climate of North Africa around 5,000 years ago made them seek out environments where humans stored water. Human habitation and the mosquitoes' environments were then very closely connected. During periods of epidemics humans are the reservoir of the virus. Because high amounts of virus are present in the blood in the beginning of acute infection, the virus can be spread from a viremic human to a mosquito, and back to a human. During other times, monkeys, birds and other vertebrates have served as reservoirs. Three genotypes of this virus have been described, each with a distinct
genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
and
antigenic In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
character: West African, East/Central/South African, and Asian genotypes. The Asian lineage originated in 1952 and has subsequently split into two lineages – India (Indian Ocean Lineage) and South East Asian clades. This virus was first reported in the Americas in 2014. Phylogenetic investigations have shown that there are two strains in Brazil – the Asian and East/Central/South African types – and that the Asian strain arrived in the Caribbean (most likely from Oceania) in about March 2013. The rate of molecular evolution was estimated to have a mean rate of 5 × 10−4 substitutions per site per year (95% higher probability density 2.9–7.9 × 10−4). Chikungunya is spread through bites from ''
Aedes ''Aedes'' is a genus of mosquitoes originally found in tropical and subtropical zones, but now found on all continents except perhaps Antarctica. Some species have been spread by human activity: ''Aedes albopictus'', a particularly invasive spe ...
'' mosquitoes, and the species '' A. aegypti'' was identified as the most common vector, though the virus has recently been associated with many other species, including '' A. albopictus''. Research by the Pasteur Institute in Paris has suggested ''Chikungunya virus'' strains in the 2005-2006
Reunion Island Reunion may refer to: * Class reunion * Family reunion Reunion, Réunion, Re-union, Reunions or The Reunion may also refer to: Places * Réunion, a French overseas department and island in the Indian Ocean * Reunion, Commerce City, Colorado, ...
outbreak incurred a mutation that facilitated transmission by the
Asian tiger mosquito ''Aedes albopictus'' (''Stegomyia albopicta''), from the mosquito (Culicidae) family, also known as the (Asian) tiger mosquito or forest mosquito, is a mosquito native to the tropical and subtropical areas of Southeast Asia. In the past few cen ...
(''A. albopictus''). Other species potentially able to transmit ''Chikungunya virus'' include '' Ae. furcifer-taylori'', '' Ae. africanus'', and '' Ae. luteocephalus''.


Mechanism

''Chikungunya virus'' is passed to humans when a bite from an infected mosquito breaks the skin and introduces the virus into the body. The pathogenesis of chikungunya infection in humans is still poorly understood, despite recent outbreaks. It appears that '' in vitro'', ''Chikungunya virus'' is able to replicate in human
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
and endothelial cells, primary fibroblasts, and monocyte-derived macrophages. Viral replication is highly cytopathic, but susceptible to type-I and -II interferon. '' In vivo'', in studies using living cells, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells, and myofibers. The type-1 interferon response seems to play an important role in the host's response to chikungunya infection. Upon infection with chikungunya, the host's fibroblasts produce type-1 alpha and beta interferon (
IFN-α The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cy ...
and
IFN-β The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cy ...
). In mouse studies, deficiencies in INF-1 in mice exposed to the virus cause increased morbidity and mortality. The chikungunya-specific upstream components of the type-1 interferon pathway involved in the host's response to chikungunya infection are still unknown. Nonetheless, mouse studies suggest that
IPS-1 Mitochondrial antiviral-signaling protein (MAVS) is a protein that is essential for antiviral innate immunity. MAVS is located in the outer membrane of the mitochondria, peroxisomes, and mitochondrial-associated endoplasmic reticulum membrane (MA ...
is an important factor, and that
IRF3 Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor. Function IRF3 is a member of the interferon regulatory transcription factor (IRF) family. IRF3 was originally discovered as a homolog of IRF1 and IRF2. ...
and
IRF7 Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors. Function IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription fac ...
are important in an age-dependent manner. Mouse studies also suggest that chikungunya evades host defenses and counters the type-I interferon response by producing NS2, a nonstructural protein that degrades
RBP1 Retinol binding protein 1, cellular, also known as RBP1, is a protein that in humans is encoded by the ''RBP1'' gene. Function RBP1 is the carrier protein involved in the transport of retinol (vitamin A alcohol) from the liver storage site to ...
and turns off the host cell's ability to transcribe DNA. NS2 interferes with the
JAK-STAT signaling pathway The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals out ...
and prevents
STAT STAT, Stat. , or stat may refer to: * Stat (system call), a Unix system call that returns file attributes of an inode * ''Stat'' (TV series), an American sitcom that aired in 1991 * Stat (website), a health-oriented news website * STAT protein, a ...
from becoming
phosphorylate In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
d. In the acute phase of chikungunya, the virus is typically present in the areas where symptoms present, specifically skeletal muscles, and joints. In the chronic phase, it is suggested that viral persistence (the inability of the body to entirely rid itself of the virus), lack of clearance of the
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
, or both, contribute to joint pain. The inflammation response during both the acute and chronic phase of the disease results in part from interactions between the virus and monocytes and macrophages. ''Chikungunya virus'' disease in humans is associated with elevated serum levels of specific
cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocr ...
and
chemokines Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additi ...
. High levels of specific cytokines have been linked to more severe acute disease:
interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...
(IL-6), IL-1β,
RANTES Chemokine (C-C motif) ligand 5 (also CCL5) is a protein which in humans is encoded by the ''CCL5'' gene. The gene has been discovered in 1990 by ''in situ'' hybridisation and it is localised on 17q11.2-q12 chromosome. It is also known as RANTES ...
, monocyte chemoattractant protein 1 (MCP-1), monokine induced by gamma interferon (MIG), and interferon gamma-induced protein 10 (IP-10). Cytokines may also contribute to chronic ''Chikungunya virus'' disease, as persistent joint pain has been associated with elevated levels of IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In those with chronic symptoms, a mild elevation of
C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 ...
(CRP) has been observed, suggesting ongoing chronic inflammation. However, there is little evidence linking chronic ''Chikungunya virus'' disease and the development of
autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
.


Viral replication

The virus consists of four nonstructural proteins and three structural proteins. The structural proteins are the capsid and two
envelope An envelope is a common packaging item, usually made of thin, flat material. It is designed to contain a flat object, such as a letter or card. Traditional envelopes are made from sheets of paper cut to one of three shapes: a rhombus, a sho ...
glycoproteins: E1 and E2, which form
heterodimeric In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ...
spikes on the viron surface. E2 binds to cellular receptors in order to enter the host cell through receptor-mediated endocytosis. E1 contains a fusion peptide which, when exposed to the acidity of the endosome in eukaryotic cells, dissociates from E2 and initiates membrane fusion that allows the release of nucleocapsids into the host cytoplasm, promoting infection. The mature virion contains 240
heterodimeric In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ...
spikes of E2/E1, which after release, bud on the surface of the infected cell, where they are released by exocytosis to infect other cells.


Diagnosis

Chikungunya is diagnosed on the basis of clinical, epidemiological, and laboratory criteria. Clinically, acute onset of high fever and severe joint pain would lead to suspicion of chikungunya. Epidemiological criteria consist of whether the individual has traveled to or spent time in an area in which chikungunya is present within the last twelve days (i.e.) the potential incubation period). Laboratory criteria include a decreased lymphocyte count consistent with
viremia Viremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to ''bacteremia'', a condition where bacteria enter the bloodstream. The name comes from combining the word "virus" wit ...
. However a definitive laboratory diagnosis can be accomplished through viral isolation, RT-PCR, or
serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
diagnosis. The differential diagnosis may include other mosquito-borne diseases, such as
dengue Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic ...
or malaria, or other infections such as influenza. Chronic recurrent polyarthralgia occurs in at least 20% of chikungunya patients one year after infection, whereas such symptoms are uncommon in dengue.
Virus isolation Viral culture is a laboratory technique in which samples of a virus are placed to different cell lines which the virus being tested for its ability to infect. If the cells show changes, known as cytopathic effects, then the culture is positive. ...
provides the most definitive diagnosis, but takes one to two weeks for completion and must be carried out in biosafety level III laboratories. The technique involves exposing specific
cell line An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cell ...
s to samples from whole blood and identifying ''Chikungunya virus''-specific responses.
RT-PCR Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase chai ...
using nested primer pairs is used to amplify several chikungunya-specific genes from whole blood, generating thousands to millions of copies of the genes in order to identify them. RT-PCR can also be used to quantify the viral load in the blood. Using RT-PCR, diagnostic results can be available in one to two days. Serological diagnosis requires a larger amount of blood than the other methods, and uses an
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presenc ...
assay to measure chikungunya-specific
IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
levels in the blood serum. One advantage offered by serological diagnosis is that serum IgM is detectable from 5 days to months after the onset of symptoms, but drawbacks are that results may require two to three days, and false positives can occur with infection due to other related viruses, such as
o'nyong'nyong virus The o'nyong'nyong virus (ONNV) was first isolated by researchers at the Uganda Virus Research Institute in Entebbe, Uganda, during a large outbreak of a disease in 1959 that resembled dengue fever. ONNV is a togavirus (family Togaviridae), genu ...
and
Semliki Forest virus The Semliki Forest virus is an alphavirus found in central, eastern, and southern Africa. It was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942 and described by Smithburn and Haddow. ...
. Presently, there is no specific way to test for chronic signs and symptoms associated with Chikungunya fever although nonspecific laboratory findings such as
C reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...
and elevated
cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocr ...
can correlate with disease activity.


Prevention

Because no approved vaccine exists, the most effective means of prevention are protection against contact with the disease-carrying mosquitoes and controlling mosquito populations by limiting their habitat. Mosquito control focuses on eliminating the standing water where mosquitos lay eggs and develop as larva; if elimination of the standing water is not possible,
insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to ...
s or biological control agents can be added. Methods of protection against contact with mosquitos include using
insect repellent An insect repellent (also commonly called "bug spray") is a substance applied to skin, clothing, or other surfaces to discourage insects (and arthropods in general) from landing or climbing on that surface. Insect repellents help prevent and cont ...
s with substances such as DEET, icaridin, PMD ( p-menthane-3,8-diol, a substance derived from the lemon eucalyptus tree), or
ethyl butylacetylaminopropionate Ethyl butylacetylaminopropionate (trade name IR3535) is an insect repellent which is applied topically to prevent bites and stings from mosquitos, ticks, and other insects. It is a colorless and almost odorless oil, has efficacy against a broad ran ...
(IR3535). However, increasing
insecticide resistance Pesticide resistance describes the decreased susceptibility of a pest population to a pesticide that was previously effective at controlling the pest. Pest species evolve pesticide resistance via natural selection: the most resistant specimens su ...
presents a challenge to chemical control methods. Wearing bite-proof long sleeves and trousers also offers protection, and garments can be treated with
pyrethroids A pyrethroid is an organic compound similar to the natural pyrethrins, which are produced by the flowers of pyrethrums (''Chrysanthemum cinerariaefolium'' and '' C. coccineum''). Pyrethroids are used as commercial and household insecticides. ...
, a class of insecticides that often has repellent properties. Vaporized pyrethroids (for example in mosquito coils) are also insect repellents. As infected mosquitoes often feed and rest inside homes, 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 outdoors.


Vaccine

, no approved vaccines are available. A phase-II vaccine trial used a live,
attenuated virus An attenuated vaccine (or a live attenuated vaccine, LAV) is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live"). Attenuation takes an infectious agent and alters it so that it becomes harmless or less ...
, to develop viral resistance in 98% of those tested after 28 days and 85% still showed resistance after one year. However, 8% of people reported transient joint pain, and attenuation was found to be due to only two mutations in the E2 glycoprotein. Alternative vaccine strategies have been developed, and show efficacy in mouse models. In August 2014 researchers at the National Institute of Allergy and Infectious Diseases in the USA were testing an experimental vaccine which uses
virus-like particle Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural pro ...
s (VLPs) instead of attenuated virus. All the 25 people participated in this phase 1 trial developed strong immune responses. As of 2015, a phase 2 trial was planned, using 400 adults aged 18 to 60 and to take place at 6 locations in the
Caribbean The Caribbean (, ) ( es, El Caribe; french: la Caraïbe; ht, Karayib; nl, De Caraïben) is a region of the Americas that consists of the Caribbean Sea, its islands (some surrounded by the Caribbean Sea and some bordering both the Caribbean S ...
. Even with a vaccine, mosquito population control and bite prevention will be necessary to control chikungunya disease. In 2021, two vaccine manufacturers, one in France, the other in the United States, reported successful completion of Phase II clinical trials.


Treatment

Currently, no specific treatment for chikungunya is available.
Supportive care Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the comfor ...
is recommended, and symptomatic treatment of fever and joint swelling includes the use of nonsteroidal anti-inflammatory drugs such as
naproxen Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formula ...
, non-aspirin
analgesics An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...
such as paracetamol (acetaminophen) and fluids.
Aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat in ...
is not recommended due to the increased risk of bleeding. Despite anti-inflammatory effects,
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
are not recommended during the acute phase of disease, as they may cause immunosuppression and worsen infection. Passive immunotherapy has potential benefit in treatment of chikungunya. Studies in animals using passive immunotherapy have been effective, and clinical studies using passive immunotherapy in those particularly vulnerable to severe infection are currently in progress. Passive immunotherapy involves administration of anti-CHIKV hyperimmune human intravenous antibodies (immunoglobulins) to those exposed to a high risk of chikungunya infection. No antiviral treatment for ''Chikungunya virus'' is currently available, though testing has shown several medications to be effective '' in vitro''.


Chronic arthritis

In those who have more than two weeks of arthritis, ribavirin may be useful. The effect of
chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...
is not clear. It does not appear to help acute disease, but tentative evidence indicates it might help those with chronic arthritis.
Steroids A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
do not appear to be an effective treatment. NSAIDs and simple
analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...
s can be used to provide partial symptom relief in most cases.
Methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
, a drug used in the treatment of rheumatoid arthritis, has been shown to have benefit in treating inflammatory polyarthritis resulting from chikungunya, though the drug mechanism for improving viral arthritis is unclear.


Prognosis

The
mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of de ...
of chikungunya is slightly less than 1 in 1000. Those over the age of 65, neonates, and those with underlying chronic medical problems are most likely to have severe complications. Neonates are vulnerable as it is possible to vertically transmit chikungunya from mother to infant during delivery, which results in high rates of morbidity, as infants lack fully developed immune systems. The likelihood of prolonged symptoms or chronic joint pain is increased with increased age and prior rheumatological disease.


Epidemiology

Historically, chikungunya has been present mostly in the developing world. The disease causes an estimated 3 million infections each year. Epidemics in the Indian Ocean, Pacific Islands, and in the Americas, continue to change the distribution of the disease. In Africa, chikungunya is spread by a
sylvatic cycle The sylvatic cycle, also enzootic or sylvatic transmission cycle, is a portion of the natural transmission cycle of a pathogen. Sylvatic refers to the occurrence of a subject in or affecting wild animals. The sylvatic cycle is the fraction of the p ...
in which the virus largely cycles between other non-human primates, small mammals, and mosquitos between human outbreaks. During outbreaks, due to the high concentration of virus in the blood of those in the acute phase of infection, the virus can circulate from humans to mosquitoes and back to humans. The transmission of the pathogen between humans and mosquitoes that exist in urban environments was established on multiple occasions from strains occurring on the eastern half of Africa in non-human primate hosts. This emergence and spread beyond Africa may have started as early as the 18th century. Currently, available data does not indicate whether the introduction of chikungunya into Asia occurred in the 19th century or more recently, but this epidemic Asian strain causes outbreaks in India and continues to circulate in Southeast Asia. In Africa, outbreaks were typically tied to heavy rainfall causing increased mosquito population. In recent outbreaks in urban centers, the virus has spread by circulating between humans and mosquitoes. Global rates of chikungunya infection are variable, depending on outbreaks. When chikungunya was first identified in 1952, it had a low-level circulation in West Africa, with infection rates linked to rainfall. Beginning in the 1960s, periodic outbreaks were documented in Asia and Africa. However, since 2005, following several decades of relative inactivity, chikungunya has re-emerged and caused large outbreaks in Africa, Asia, and the Americas. In India, for instance, chikungunya re-appeared following 32 years of absence of viral activity. Outbreaks have occurred in Europe, the Caribbean, and South America, areas in which chikungunya was not previously transmitted. Local transmission has also occurred in the United States and Australia, countries in which the virus was previously unknown. In 2005, an outbreak on the island of
Réunion Réunion (; french: La Réunion, ; previously ''Île Bourbon''; rcf, label= Reunionese Creole, La Rényon) is an island in the Indian Ocean that is an overseas department and region of France. It is located approximately east of the island o ...
was the largest then documented, with an estimated 266,000 cases on an island with a population of approximately 770,000. In a 2006 outbreak, India reported 1.25 million suspected cases. Chikungunya was recently introduced to the Americas, and from 2013 to 2014 in the Americas, 1,118,763 suspected cases and 24,682 confirmed cases were reported by the
PAHO The Pan American Health Organization (PAHO) is an international public health agency working to improve the health and living standards of the people of the Americas. It is part of the United Nations system, serving as the Regional Office for ...
. An analysis of the genetic code of ''Chikungunya virus'' suggests that the increased severity of the 2005–present outbreak may be due to a change in the genetic sequence which altered the E1 segment of the virus' viral coat protein, a variant called E1-A226V. This mutation potentially allows the virus to multiply more easily in mosquito cells. The change allows the virus to use the
Asian tiger mosquito ''Aedes albopictus'' (''Stegomyia albopicta''), from the mosquito (Culicidae) family, also known as the (Asian) tiger mosquito or forest mosquito, is a mosquito native to the tropical and subtropical areas of Southeast Asia. In the past few cen ...
(an invasive species) as a vector in addition to the more strictly
tropical The tropics are the regions of Earth surrounding the Equator. They are defined in latitude by the Tropic of Cancer in the Northern Hemisphere at N and the Tropic of Capricorn in the Southern Hemisphere at S. The tropics are also referred to ...
main vector, ''
Aedes aegypti ''Aedes aegypti'', the yellow fever mosquito, is a mosquito that can spread dengue fever, chikungunya, Zika fever, Mayaro and yellow fever viruses, and other disease agents. The mosquito can be recognized by black and white markings on its l ...
''. 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 albopictus'' is an invasive species which has spread through Europe, the Americas, the Caribbean, Africa and the Middle East. After the detection of
zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, wh ...
in Brazil in April 2015, the first ever in the Western Hemisphere, it is now thought some chikungunya and dengue cases could in fact be zika virus cases or
coinfection Coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with he ...
s.


History

The word 'chikungunya' is believed to have been derived from a description in the
Makonde language Makonde, or Kimakonde, is the language spoken by the Makonde people, Makonde, an ethnic group in southeast Tanzania and northern Mozambique. Makonde is a central Bantu language closely related to Yao language, Yao. The Matambwe language, Matambw ...
, meaning "that which bends up", of the contorted
posture Posture or posturing may refer to: Medicine * Human position ** Abnormal posturing, in neurotrauma ** Spinal posture ** List of human positions * Posturography, in neurology Other uses * Posture (psychology) In humans, posture can provide a ...
of people affected with the severe joint pain and
arthritic Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some ...
symptoms associated with this disease. The disease was first described by Marion Robinson and W.H.R. Lumsden in 1955, following an outbreak in 1952 on the
Makonde Plateau The Makonde Plateau, also known as the Newala Plateau, is a plateau in southeastern Tanzania. It is mostly within Mtwara Region, with the northeast corner in Lindi Region. The Makonde Plateau is a roughly rectangular, rising from the coast west ...
, along the border between Mozambique and
Tanganyika Tanganyika may refer to: Places * Tanganyika Territory (1916–1961), a former British territory which preceded the sovereign state * Tanganyika (1961–1964), a sovereign state, comprising the mainland part of present-day Tanzania * Tanzania Main ...
(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 A gloss is a brief notation, especially a marginal one or an interlinear one, of the meaning of a word or wording in a text. It may be in the language of the text or in the reader's language if that is different. A collection of glosses is a ' ...
the Makonde term more specifically as "that which bends up". Subsequent authors apparently overlooked the references to the Makonde language and assumed the term to have been derived from Swahili, the '' lingua franca'' of the region. The erroneous attribution to Swahili has been repeated in numerous print sources. Many erroneous spellings of the name of the disease are also in common use. Since its discovery in
Tanganyika Tanganyika may refer to: Places * Tanganyika Territory (1916–1961), a former British territory which preceded the sovereign state * Tanganyika (1961–1964), a sovereign state, comprising the mainland part of present-day Tanzania * Tanzania Main ...
, 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. This is in agreement with the molecular genetics evidence that suggests it evolved around the year 1700.


Research

Chikungunya is one of more than a dozen agents researched as a potential
biological weapon A biological agent (also called bio-agent, biological threat agent, biological warfare agent, biological weapon, or bioweapon) is a bacterium, virus, protozoan, parasite, fungus, or toxin that can be used purposefully as a weapon in bioterroris ...
.Chemical and Biological Weapons: Possession and Programs Past and Present
", James Martin Center for Nonproliferation Studies,
Middlebury College Middlebury College is a private liberal arts college in Middlebury, Vermont. Founded in 1800 by Congregationalists, Middlebury was the first operating college or university in Vermont. The college currently enrolls 2,858 undergraduates from all 5 ...
, 9 April 2002, accessed 18 June 2014.
This disease is part of the group of
neglected tropical diseases Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bact ...
.


See also

*
Coalition for Epidemic Preparedness Innovations The Coalition for Epidemic Preparedness Innovations (CEPI) is a foundation that takes donations from public, private, philanthropic, and civil society organisations, to finance independent research projects to develop vaccines against emerging ...
* Epidemiology of chikungunya


References


Works cited

* *


External links


Chikungunya fact sheet
��from the World Health Organization (WHO)
Chikungunya outbreaks
��from the World Health Organization (WHO)
Togaviridae
��from the Virus Pathogen Database and Analysis Resource (ViPR) *
Chikungunya in Cuba

Chikungunya: The key role of "innate immunity"
{{Taxonbar, from=Q15794049 Biological weapons Health disasters in India Tropical diseases