Chikungunya

Chikungunya can be asymptomatic, with estimates of between 17% and 40% of infections showing no symptoms. People with chikungunya also frequently experience headaches, back pain, nausea, and fatigue. Some people experience gastrointestinal issues, with abdominal pain and vomiting. Others experience eye problems, namely sensitivity to light, conjunctivitis, and pain behind the eye. 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. Joints are more likely to be affected if they have previously been damaged by disorders such as arthritis. Temporary damage to the liver may occur. 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. Newborns, the elderly, and those with diabetes, heart disease, liver and kidney diseases, and HIV 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. 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). Because large 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. The incubation period ranges from one to twelve days and is most typically three to seven days. 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. ==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. It takes about a week before the host's adaptive immune system begins to develop antibodies which eventually clear the virus from the bloodstream. However the virus can persist within specific tissues, especially the joints, causing long term inflammation and pain in chronic cases. 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. == Diagnosis ==

Diagnosing chikungunya can be difficult because its symptoms, such as sudden fever and joint pain, closely resemble other mosquito-borne illnesses like dengue fever and malaria. Chikungunya should be suspected if a patient with these symptoms either lives in an area where the virus is endemic, or if they have recently traveled to such an area. During the first week of illness, when virus is present in the bloodstream, it is possible to detect viral RNA in a blood sample using techniques such as reverse transcription-polymerase chain reaction (RT-PCR) or viral culture. Other infections which should be considered include malaria, leptospirosis, measles, mononucleosis and African tick bite fever, which are often endemic in the same areas and can have similar symptoms. It is possible for a patient to be infected by more than one virus simultaneously. ==Prevention==

Although an approved vaccine exists, the most effective means of prevention is to avoid or prevent mosquito bites. The main strategies for this are: controlling mosquito populations by limiting their habitat; and protection against contact with disease-carrying mosquitoes. Individuals should use mosquito repellent, as well as barriers such as loose clothing that covers the arms and legs, mosquito nets and window and door screens. Once immunity against chikungunya has been acquired, whether as a result of infection or vaccination, it endures long term and may be lifelong. Vaccination ==Treatment==

No specific treatment for chikungunya is available. Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen should not be used in the acute phase until dengue fever has been ruled out, as these can increase the risk of bleeding in dengue. ==Prognosis==

The mortality rate of chikungunya is slightly less than 1 in 1000. Those over the age of 65, infants, and those with underlying chronic medical problems are most likely to have severe complications. Newborn infants are especially vulnerable as they lack fully developed immune systems, and may pick up the infection through vertical transmission from their mother. ==Epidemiology==

(CDC) as of September 2019. Chikungunya virus is transmitted by the bite of an infected mosquito of the genus Aedes, specifically Aedes aegypti and ''Aedes albopictus. In Africa, chikungunya virus is maintained by a sylvatic cycle in which the virus cycles between small mammals (principally non-human primates), and mosquitos; humans can be infected by a mosquito bite but the virus does not rely on humans for survival. , 119 countries and territories, principally those in tropical and subtropical regions, have reported local transmission of chikungunya. In some of these it is endemic (continually present). In some regions the disease tends to manifest as periodic epidemics which can be sudden and intense, as the virus spreads among a population with a low level of herd immunity. Because of the difficulty in reliably diagnosing chikungunya disease, especially in resource poor contexts, there are no reliable statistics on its incidence. However epidemiological modelling studies estimate between 14.4 million and 35 million people are infected annually. Up to 848,000 people experience chronic long-term pain; annual mortality is estimated at up to 3,700 deaths. ==History==

The term chikungunya is derived from the Makonde root verb kungunyala, meaning to dry up or become contorted, descriptive of the posture of people with chronic symptoms. The disease was first clearly described by Marion Robinson and W.H.R. Lumsden At that time, it was endemic to sub-saharan Africa, relying on A. aegypti to maintain its sylvatic cycle. Prior to this, the disease may have caused sporadic epidemics in other regions, which had been incorrectly ascribed to dengue. The first direct evidence of chikungunya spreading outside of Africa came from Bangkok, Thailand, in 1958, during an urban outbreak. It subsequently appeared in India and Cambodia in the early 1960s, associated with the spread of the A. aegypti mosquito to those regions. An outbreak on the coast of Kenya in 2004 rapidly spread to the islands of the Indian Ocean (such as La Réunion) in 2005, then to India and Southeast Asia where it caused explosive outbreaks affecting millions of people. Infected air travelers carried the virus into areas where the population had not previously been exposed to the disease and had no immunity. A. albopictus is an invasive species which since the 1960's has spread through parts of Europe, the Americas, the Caribbean, Africa, and the Middle East. Chikungunya was introduced to the Americas in 2013, first detected on the French island of Saint Martin, ==Research directions==

Chikungunya is recognised as a global threat; there are an estimated 35 million cases annually, with 2.8 billion people living in areas which are threatened by the disease. It is classed as a priority pathogen by the Coalition for Epidemic Preparedness Innovations (CEPI). Research on chikungunya focuses on improving knowledge of the mechanism of the disease and developing tools for its prevention, diagnosis and treatment. • Prevention of chikungunya is principally focused on the development and testing of vaccines. , two vaccines are available; each of them gives long lasting protection after administration of a single dose. Other vaccine candidates are under development. • Reliable diagnosis of chikungunya is difficult, slow and expensive. Research is under way to develop diagnostic tools which are cheaper, quicker and easier to use. • There is no effective antiviral treatment for chikungunya. Research directions include repurposing some existing licensed drugs and modifying plant-derived compounds. • For many, the sequelae of chikungunya can persist for month or years, and range from mild discomfort to severe and debilitating joint pain which severely affects their physical and mental well being. Research in to the underlying mechanism of long term pain, and its possible treatments, is ongoing. ==Chikungunya virus==

Virology 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. 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, O'nyong'nyong virus, and Semliki Forest virus. 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, and work requires biosafety level III precautions. 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. 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. 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). 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. 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. == References ==