Chikungunya

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Chikungunya
2012-01-09 Chikungunya on the right feet at The Philippines.jpeg
Rash from chikungunya
Pronunciation
Specialty Infectious disease
Symptoms Fever, joint pain, headache, muscle pain, joint swelling, and rash. [2]
Complications Long term joint pain [2]
Usual onset2 to 14 days after exposure [3]
DurationUsually less than a week [2]
Causes Chikungunya virus spread by mosquitoes [3]
Diagnostic method Blood test for viral RNA or antibodies [3]
Differential diagnosis Dengue fever, Zika fever [3]
Prevention Chikungunya vaccine, Mosquito control, avoidance of bites [4]
Treatment Supportive care [3]
Prognosis Risk of death ~ 1 in 1,000 [4]
Frequency> 1 million (2014) [3]

Chikungunya is an infection caused by the chikungunya virus. [3] The most common symptoms are fever and joint pain, [2] typically occurring four to eight days after the bite of an infected mosquito; [3] however some people may be infected without showing any symptoms. [5] Other symptoms may include headache, muscle pain, joint swelling, and a rash. [2] Symptoms usually improve within a week; however, occasionally the joint pain may last for months or years. [2] [6] The very young, old, and those with other health problems are at risk of more severe disease. [2]

Contents

The virus is spread between people by two species of mosquito in the Aedes genus: Aedes albopictus and Aedes aegypti , [3] which mainly bite during the day, [7] [8] particularly around dawn and in the late afternoon. [9] The virus may circulate within a number of animals, including birds and rodents. [3] Diagnosis is done by testing the blood for either viral RNA or antibodies to the virus. [3] The symptoms can be mistaken for those of dengue fever and Zika fever, which are spread by the same mosquitoes. [3] It is believed most people become immune after a single infection. [2]

The best means of prevention are overall mosquito control and the avoidance of bites in areas where the disease is common. [4] This may be partly achieved by decreasing mosquitoes' access to water, as well as the use of insect repellent and mosquito nets. Chikungunya vaccines have been approved for use in the United States [10] and in the European Union. [11] [12] [13] No specific treatment for chikungunya is available; supportive care is recommended, with symptomatic treatment of fever and joint swelling. [4]

The chikungunya virus is widespread in tropical and subtropical regions where warm climates and abundant populations of its mosquito vectors (A. aegypti and A. albopictus) facilitate its transmission. [3] The disease was first identified in 1952 in Tanzania and named based on the Makonde words for "to become contorted". [3] While the disease is endemic in Africa and Asia, outbreaks have been reported in Europe and the Americas since the 2000s. [3] In 2014, more than a million suspected cases occurred globally. [3] Chikungunya has become a global health concern due to its rapid geographic expansion, recurrent outbreaks, the lack of effective antiviral treatments, and potential to cause severe symptoms and death. [14]

Signs and symptoms

Chikungunya can be asymptomatic, with estimates of between 17% and 40% of infections showing no symptoms. [5] For those experiencing symptoms, they typically begin with a sudden high fever above 39 °C (102 °F) around 3 to 7 days after the bite of an infected mosquito. [15] [5] The fever is often accompanied by severe muscle and joint pain, which affects multiple joints in the arms and legs and is often symmetric – i.e. if one elbow is affected, the other is as well. [16] [5] People with chikungunya also frequently experience headaches, back pain, nausea, and fatigue. [16] Around half of those affected develop a rash, with reddening and sometimes small bumps on the palms, foot soles, torso, and face. [16]

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. [15] Some people experience gastrointestinal issues, with abdominal pain and vomiting. Others experience eye problems, namely sensitivity to light, conjunctivitis, and pain behind the eye. [16] This first set of symptoms – called the "acute phase" of chikungunya – lasts around a week, after which most symptoms resolve on their own. [16]

For those with severe symptoms, approximately 30% to 40% continue to have symptoms after the "acute phase" resolves. [5] [16] The lasting symptoms tend to be joint pains: arthritis, tenosynovitis, and/or bursitis. [16] If the affected person has pre-existing joint issues, these tend to worsen. [16] Overuse of a joint can result in painful swelling, stiffness, nerve damage, and neuropathic pain. [16] Typically the joint pain improves with time; however, the chronic stage can last anywhere from a few months to several years. [16]

Almost all symptomatic cases feature joint pain, generally in more than one joint. [17] 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. [17] [18] Joints are more likely to be affected if they have previously been damaged by disorders such as arthritis. [18] Pain may also occur in the muscles or ligaments. In more than half of cases, normal activity is limited by significant fatigue and pain. [17] Infrequently, inflammation of the eyes may occur in the form of iridocyclitis, or uveitis, and retinal lesions may occur. [19] Temporary damage to the liver may occur. [20]

People with chikungunya occasionally develop long term neurologic disorders, most frequently swelling or degeneration of the brain, inflammation or degeneration of the myelin sheaths around neurons, Guillain–Barré syndrome, acute disseminated encephalomyelitis, hypotonia (in newborns), and issues with visual processing. [16]

Newborns, the elderly, and those with diabetes, heart disease, liver and kidney diseases, and human immunodeficiency virus infection tend to have more severe cases of chikungunya. Fewer than 1 in 1,000 people with symptomatic chikungunya die of the disease; generally these are people with pre-existing health conditions. [16] [5]

Transmission

Chikungunya is generally transmitted from mosquitoes to humans. Chikungunya is spread through bites from Aedes mosquitoes, specifically A. aegypti (Egyptian mosquito) and A. albopictus (Tiger mosquito). [3] Because high amounts of virus are present in the blood during the first few days of infection, the virus can spread from an infected human to a mosquito, where it replicates without harming the mosquito. Subsequently, a bite from the infected mosquito will transmit the virus back to a human. [3] The incubation period ranges from one to twelve days and is most typically three to seven. [17]

Rarely, the disease can be transmitted from mother to child during pregnancy or at birth, in women who become infected a few days before delivery. [5]

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 virus initially replicates in cells near the location of the bite; from here it enters the lymphatic system and the bloodstream, enabling it to circulate to organs and tissues which become infected. Most frequently it reproduces in the lymphatic system and the spleen, as well as peripheral joints, muscles and tendons where symptoms frequently occur; it appears that the virus is able to penetrate and replicate in many different types of cells. [21] In severe cases it can infect the brain and liver. [22] [21]

During the acute phase of infection, large numbers of infectious virus particles are present in the bloodstream, making it very likely that an uninfected mosquito will pick up the virus if it bites the human host. [22] [21]

During the first few days of infection, the host's innate immune system is activated, producing type I interferons and inflammatory cytokines to fight the infection. This generates the fever and localised inflammation which is characteristic of the disease. [21] [23] It takes about a week before the host's adaptive immune system begins to develop antibodies which eventually clear the virus from the bloodstream. [24] However the virus can persist within specific tissues, especially the joints, causing long term inflammation and pain in chronic cases. [23]

The virus has mechanisms which help it to evade the immune response. Within an infected cell, the viral nonstructural protein 2 (nsP2) interferes with the JAK-STAT signalling pathway to hinder it from triggering an antiviral response. [25] The virus can induce apoptosis (programmed cell death) in host cells; virus laden debris from apoptosis is engulfed by macrophages which in turn become infected. [26] The virus also seems to be able to evade T lymphocytes which seek to target and destroy the virus particles. [27]

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. However a definitive laboratory diagnosis can be accomplished through viral isolation, RT-PCR, or serological diagnosis. [28]

The differential diagnosis may include other mosquito-borne diseases, such as dengue 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. [29]

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. [30] 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, generating thousands to millions of copies of the genes to identify them. RT-PCR can also quantify the viral load in the blood. Using RT-PCR, diagnostic results can be available in one to two days. [30] For rapid identification and genotyping of the chikungunya virus, a method combining RT-PCR with restriction fragment length polymorphism (RFLP) analysis can be used. It is based on amplifying a specific 648 bp fragment of the nsP2 gene, encoding nonstructural protein 2. The unique pattern of restriction sites for the endonucleases PspEI, PvuII, and DraI within this fragment allows for the discrimination of the four major virus genotypes. [31]

Serological diagnosis requires a larger amount of blood than the other methods and uses an ELISA assay to measure chikungunya-specific IgM 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 and Semliki Forest virus. [30]

Presently,[ when? ] 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 and elevated cytokines can correlate with disease activity. [32]

Prevention

A. aegypti mosquito biting a person Aedes aegypti biting human.jpg
A. aegypti mosquito biting a person

Although an approved vaccine exists, the most effective means of prevention are protection against contact with disease-carrying mosquitoes and controlling mosquito populations by limiting their habitat. [4]  Access to the chikungunya vaccine remains limited in many endemic regions.[ citation needed ] Mosquito control focuses on eliminating standing water where mosquitos lay eggs and develop as larvae. [33]

Vaccination

This section is an excerpt from Chikungunya vaccine.[ edit ]

Chikungunya vaccines are vaccines intended to provide acquired immunity against the chikungunya virus. [34] [35]

The most commonly reported side effects include headache, fatigue, muscle pain, joint pain, fever, nausea and tenderness at the injection site. [36]

The first chikungunya vaccine was approved for medical use in the United States in November 2023. [36] Chikungunya vaccines were also authorized in the European Union in May 2024. [37] [38] [39]

Treatment

No specific treatment for chikungunya is available. [4] Supportive care is recommended, and symptomatic treatment of fever and joint swelling includes the use of nonsteroidal anti-inflammatory drugs such as naproxen, non-aspirin analgesics such as paracetamol (acetaminophen) and fluids. [4] [5] Aspirin is not recommended due to the increased risk of bleeding. Despite anti-inflammatory effects, corticosteroids are not recommended [5] during the acute phase of disease, as they may cause immunosuppression and worsen infection. [18]

Chronic arthritis

In those who have more than two weeks of arthritis, ribavirin may be useful. [4] The effect of chloroquine is not clear. [4] It does not appear to help acute disease, but tentative evidence indicates it might help those with chronic arthritis. [4] Steroids do not appear to be an effective treatment. [4] NSAIDs and simple analgesics can be used to provide partial symptom relief in most cases. Methotrexate, a drug used in the treatment of rheumatoid arthritis, has been shown to have a benefit in treating inflammatory polyarthritis resulting from chikungunya, though the drug mechanism for improving viral arthritis is unclear. [40]

Prognosis

The mortality rate of chikungunya is slightly less than 1 in 1000. [41] Those over the age of 65, infants, and those with underlying chronic medical problems are most likely to have severe complications. [42] Newborn infants are especially vulnerable as they lack fully developed immune systems, and may pick up the infection through vertical transmission from their mother. [42] The likelihood of prolonged symptoms or chronic joint pain is increased with increased age and prior rheumatological disease. [43] [44]

Epidemiology

Dark green denotes countries with current or previous local transmission of chikungunya virus, per US Centers for Disease Control and Prevention (CDC) as of September 2019. CHIK-World-Map-09-17-2019.jpg
Dark green denotes countries with current or previous local transmission of chikungunya virus, per US Centers for Disease Control and Prevention (CDC) as of September 2019.
A. albopictus distribution as of December 2007 Dark blue: Native range Teal: introduced Albopictus distribution 2007.png
A. albopictus distribution as of December 2007
Dark blue: Native range
Teal: introduced

Historically, chikungunya has been present mostly in the developing world. The disease causes an estimated 3 million infections each year. [45] Epidemics in the Indian Ocean, Pacific Islands, and in the Americas, continue to change the distribution of the disease. [46] In Africa, chikungunya is spread by a sylvatic cycle in which the virus largely cycles between other non-human primates, small mammals, and mosquitos between human outbreaks. [47]

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. [47] 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. [33] This emergence and spread beyond Africa may have started as early as the 18th century. [33]

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. [33] 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. [18]

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. 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. [48]

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. [18] In 2005, an outbreak on the island of Réunion was the largest then documented, with an estimated 266,000 cases on an island with a population of approximately 770,000. [49] In a 2006 outbreak, India reported 1.25 million suspected cases. [50]

Chikungunya was introduced to the Americas in 2013, first detected on the French island of Saint Martin, [51] and for the next two years in the Americas, 1,118,763 suspected cases and 24,682 confirmed cases were reported by the PAHO. [52] In 2023, Brazil experienced a significant outbreak, with over 180,000 cases reported, prompting intensified public health interventions and renewed research efforts on viral mutations and transmission patterns [53]

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. [54] The change allows the virus to use Aedes albopictus as a vector in addition to the more strictly tropical main vector, Aedes aegypti . [55] Enhanced transmission of chikungunya virus by A. albopictus could mean an increased risk for outbreaks in other areas where the mosquito is present. [56] A. albopictus is an invasive species which since the 1960's has spread through Europe, the Americas, the Caribbean, Africa, and the Middle East. [57]

After the detection of zika virus in Brazil in April 2015, the first ever in the Western Hemisphere, [58] [59] it is now[ when? ] thought some chikungunya and dengue cases could in fact be zika virus cases or coinfections.[ citation needed ]

Since the start of 2025, and as of 25 February, more than 30,000 chikungunya virus cases and 14 related deaths have been reported across 14 countries and territories in the Americas, Africa, Asia, and Europe. [60]

History

The disease was first described by Marion Robinson [61] and W.H.R. Lumsden [62] in a pair of 1955 papers, following an outbreak in 1952 on the Makonde Plateau, along the border between Mozambique and Tanganyika (the mainland part of modern-day Tanzania). Since then outbreaks have occurred occasionally in Africa, South Asia, and Southeast Asia; recent outbreaks have spread the disease over a wider range.[ citation needed ]

The first recorded outbreak may have been in 1779. [63] This is in agreement with the molecular genetics evidence that suggests it evolved around the year 1700. [64]

According to the original paper by Lumsden, the term 'chikungunya' is derived from the Makonde root verb kungunyala, meaning to dry up or become contorted. In concurrent research, Robinson[ citation needed ] glossed the Makonde term more specifically as "that which bends up". It is understood to refer to the contorted posture of people affected with severe joint pain and arthritic symptoms associated with this disease. [65] Subsequent authors overlooked the references to the Makonde language and assumed the term to have been derived from Swahili, the lingua franca of the region and part of a different branch of Bantu languages. The erroneous attribution to Swahili has been repeated in numerous print sources. [66]

In July 2025, a severe outbreak occurred in China’s Guangdong province. Seven thousand people tested positive for the disease, although symptoms were said to be minor for 95% of those people. [67]

Research

Chikungunya is one of more than a dozen agents researched as a potential biological weapon. [68] [69]

This disease is part of the group of neglected tropical diseases. [70]

Chikungunya virus

Virology

Chikungunya virus
Chikungunya Virus.png
Chikungunya virus structure at atomic resolution. Bar = 100 Å [71]
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Alsuviricetes
Order: Martellivirales
Family: Togaviridae
Genus: Alphavirus
Species:
Alphavirus chikungunya

Chikungunya virus is a member of the genus Alphavirus , and family Togaviridae . Chikungunya virus features an icosahedral capsid surrounded by a lipid envelope, with a diameter ranging from 60 to 70 nm. [72] It was first isolated in 1953 in Tanzania and is an RNA virus with a positive-sense single-stranded genome of about 11.6kb. [73] It is a member of the Semliki Forest virus complex and is closely related to Ross River virus, O'nyong'nyong virus, and Semliki Forest virus. [74] Because it is transmitted by arthropods, namely mosquitoes, it can also be referred to as an arbovirus (arthropod-borne virus). In the United States, it is classified as a category B priority pathogen, [75] and work requires biosafety level III precautions. [76]

Three genotypes of this virus have been described, each with a distinct genotype and antigenic character: West African, East/Central/South African, and Asian genotypes. [77] 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 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. [78] 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). [78]

The chikungunya virus genome consists of structural and non-structural proteins as typical of alphavirus genomic organization. [79] The structural proteins, including the capsid, E3, E2, 6K and E1, are responsible for encapsulating the viral genome and assembling new viral particles. These proteins are critical for viral entry into host cells. Meanwhile, the non-structural proteins, nsP1, nsP2, nsP3, and nsP4, play essential roles in viral replication, translation, and immune evasion. [79]

Viral replication

Transmission electron micrograph of chikungunya virus particles Chikungunya virus particles-PHIL-17369.jpg
Transmission electron micrograph of chikungunya virus particles

The virus consists of four nonstructural proteins and three structural proteins. [33] The structural proteins are the capsid and two envelope glycoproteins: E1 and E2, which form heterodimeric 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. [80] The mature virion contains 240 heterodimeric 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. [73]

See also

References

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