Chikungunya is an infection caused by the Alphavirus chikungunya (CHIKV).[7][8][5] The disease was first identified in 1952 in Tanzania and named based on the Kimakonde words for "to become contorted".[5]
Symptoms include fever and joint pain.[4] These typically occur two to twelve days after exposure.[5] Other symptoms may include headache, muscle pain, joint swelling, and a rash.[4] Symptoms usually improve within a week; however, occasionally the joint pain may last for months or years.[4][9] The risk of death is around 1 in 1,000.[6] The very young, old, and those with other health problems are at risk of more severe disease.[4]
The virus is spread between people by two types of mosquitos: Aedes albopictus and Aedes aegypti,[5] which mainly bite during the day.[10] The virus may circulate within a number of animals, including birds and rodents.[5] Diagnosis is done by either testing the blood for viral RNA or antibodies to the virus.[5] The symptoms can be mistaken for those of dengue fever and Zika fever.[5] It is believed most people become immune after a single infection.[4]
The best means of prevention are overall mosquito control and the avoidance of bites in areas where the disease is common.[6] This may be partly achieved by decreasing mosquitoes' access to water, as well as the use of insect repellent and mosquito nets. In November 2023 the USFDA approved an adults-only vaccine (Ixchiq) for prevention of the disease.[11] Once infected and symptomatic, recommendations to patients should include rest, fluids, and medications to help with fever and joint pain.[4][5]
In 2014, more than a million suspected cases occurred globally.[5] While the disease is endemic in Africa and Asia, outbreaks have been reported in Europe and the Americas since the 2000s;[5] in 2014, an outbreak was reported in Florida in the continental United States, but as of 2016 there were no further locally-acquired cases.[12][13]
Around 85% of people infected with chikungunya virus experience symptoms, typically beginning with a sudden high fever above 39 °C (102 °F).[14] The fever is soon followed by severe muscle and joint pain.[15] 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.[15] People with chikungunya also frequently experience headache, back pain, nausea, and fatigue.[15] Around half of those affected develop a rash, with reddening and sometimes small bumps on the palms, foot soles, torso, and face.[15] 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.[14] Some people experience gastrointestinal issues, with abdominal pain and vomiting. Others experience eye problems, namely sensitivity to light, conjunctivitis, and pain behind the eye.[15] This first set of symptoms – called the "acute phase" of chikungunya – lasts around a week, after which most symptoms resolve on their own.[15]
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.[15] In both cases, the lasting symptoms tend to be joint pains: arthritis, tenosynovitis, and/or bursitis.[15] If the affected person had pre-existing joint issues, these tend to worsen.[15] Overuse of a joint can result in painful swelling, stiffness, nerve damage, and neuropathic pain.[15] Typically the joint pain improves with time; however, the chronic stage can last anywhere from a few months to several years.[15]
Joint pain is reported in 87–98% of cases, and nearly always occurs in more than one joint, though joint swelling is uncommon.[16] 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.[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.[16][17] Pain may also occur in the muscles or ligaments. In more than half of cases, normal activity is limited by significant fatigue and pain.[16] Infrequently, inflammation of the eyes may occur in the form of iridocyclitis, or uveitis, and retinal lesions may occur.[18] Temporary damage to the liver may occur.[19]
People with chikungunya occasionally develop 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.[15] In particularly rare cases, people may develop behavioral changes, seizures, irritation of the cerebellum or meninges, oculomotor nerve palsy, or paralysis of the eye muscles.[15]
Newborns are susceptible to particularly severe effects of Chikungunya infection. Signs of infection typically begin with fever, rash, and swelling in the extremities.[15] 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 seizures.[15] In severe cases, affected newborns may also have issues with bleeding and bloodflow, and problems with heart function.[15]
In addition to 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. Around 1 to 5 in 1,000 people with symptomatic Chikungunya die of the disease.[15]
Chikungunya virus (CHIKV), is a member of the genus Alphavirus, and family Togaviridae. It was first isolated in 1953 in Tanzania and is an RNA virus with a positive-sense single-stranded genome of about 11.6kb.[21] 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.[22] 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,[23] and work requires biosafety level III precautions.[24]
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.[17] The incubation period ranges from one to twelve days, and is most typically three to seven.[16]
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.[25] During other times, monkeys, birds and other vertebrates have served as reservoirs.[26] 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.[27] 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.[28] 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).[28]
Chikungunya is spread through bites from Aedes 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.[17] 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).[29] Other species potentially able to transmit Chikungunya virus include Ae. furcifer-taylori, Ae. africanus, and Ae. luteocephalus.[17]
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 and endothelial cells, primary fibroblasts, and monocyte-derived macrophages. Viral replication is highly cytopathic, but susceptible to type-I and -II interferon.[30] In vivo, in studies using living cells, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells, and myofibers.[31][32][33]
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 and IFN-β).[8][32] In mouse studies, deficiencies in INF-1 in mice exposed to the virus cause increased morbidity and mortality.[32][34][35] The chikungunya-specific upstream components of the type-1 interferon pathway involved in the host's response to chikungunya infection are still unknown.[36] Nonetheless, mouse studies suggest that IPS-1 is an important factor,[36] and that IRF3 and IRF7 are important in an age-dependent manner.[37][38] 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 and turns off the host cell's ability to transcribe DNA.[39] NS2 interferes with the JAK-STAT signaling pathway and prevents STAT from becoming phosphorylated.[40]
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, 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.[41] Chikungunya virus disease in humans is associated with elevated serum levels of specific cytokines and chemokines. High levels of specific cytokines have been linked to more severe acute disease: interleukin-6 (IL-6), IL-1β, 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).[25] In those with chronic symptoms, a mild elevation of C-reactive protein (CRP) has been observed, suggesting ongoing chronic inflammation. However, there is little evidence linking chronic Chikungunya virus disease and the development of autoimmunity.[citation needed][42]
