Chikungunya
Encyclopedia
Chikungunya virus (CHIKV) is an insect-borne virus
Arbovirus
Arbovirus is a term used to refer to a group of viruses that are transmitted by arthropod vectors. The word arbovirus is an acronym . Some arboviruses are able to cause emergent disease.-Transmission:...

, of the genus Alphavirus
Alphavirus
In biology and immunology, an alphavirus belongs to the group IV Togaviridae family of viruses, according to the system of classification based on viral genome composition introduced by David Baltimore in 1971. Alphaviruses, like all other group IV viruses have a positive sense single stranded RNA...

, that is transmitted to humans by virus-carrying Aedes
Aedes
Aedes is a genus of mosquito originally found in tropical and subtropical zones, but now found on all continents excluding Antarctica. Some species have been spread by human activity. Aedes albopictus, a most invasive species was recently spread to the New World, including the U.S., by the used...

mosquitoes. There have been recent breakouts of CHIKV associated with severe illness. CHIKV infection causes an illness with symptoms similar to dengue fever
Dengue fever
Dengue fever , also known as breakbone fever, is an infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles...

, with an acute febrile phase of the illness lasting only two to five days, followed by a prolonged arthralgic
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....

 disease that affects the joints of the extremities. The pain associated with CHIKV infection of the joints persists for weeks or months, or in some cases years.

Signs and symptoms

The incubation period of Chikungunya disease is from two to five days. Symptoms of the disease include a fever up to 40 °C (104 °F), a petechial or maculopapular
Maculopapular rash
A maculopapular rash is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. The term "maculopapular" is a compound: macules are small, flat discolored spots on the surface of the skin; and papules are small, raised bumps...

 rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...

 of the trunk and occasionally the limbs, and arthralgia or arthritis affecting multiple joints. Other nonspecific symptoms can include headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...

, and slight photophobia
Photophobia
Photophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...

. Typically, the fever lasts for two days and then ends abruptly. However, other symptoms—namely joint pain, intense headache, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

 and an extreme degree of prostration—last for a variable period; usually for about 5 to 7 days. Patients have complained of joint pains for much longer time periods; some as long as 2 years, depending on their age.

Diagnosis

Common laboratory tests for chikungunya include RT-PCR, virus isolation, and serological tests.
  • Virus isolation provides the most definitive diagnosis but takes 1–2 weeks for completion and must be carried out in Biosafety level 3 laboratories. The technique involves exposing specific cell lines to samples from whole blood and identifying chikungunya virus-specific responses.
  • RT-PCR using nested primer pairs to amplify several Chikungunya-specific gene
    Gene
    A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

    s from whole blood. Results can be determined in 1–2 days.
  • Serological diagnosis requires a larger amount of blood than the other methods and uses an ELISA
    ELISA
    Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

     assay to measure Chikungunya-specific IgM
    IGM
    IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...

     levels. Results require 2–3 days and false positives can occur with infection via other related viruses such as O'nyong'nyong virus
    O'nyong'nyong virus
    The O'nyong'nyong virus or O'nyong-nyong virus is a virus first isolated by the Uganda Virus Research Institute in Entebbe, Uganda in 1959. It is a togavirus , genus Alphavirus and is closely related to the Chikungunya and Igbo Ora viruses. The name comes from the Nilotic language of Uganda and...

     and Semliki Forest Virus
    Semliki Forest Virus
    The Semliki Forest virus was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942. It is known to cause disease in both animals and man...

    .

Causes

Chikungunya virus is indigenous to tropical Africa and Asia, where it is transmitted to humans by the bite of infected mosquitoes, usually of the genus Aedes. Chikungunya virus belongs to alphavirus genus of the Togaviridae
Togaviridae
The Togaviridae are a family of viruses, including the following genera:* Genus Alphavirus; type species: Sindbis virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Ross River virus, O'nyong'nyong virus, Chikungunya* Genus Rubivirus;...

 family. It is an "Arbovirus" (Ar-arthropod, bo-borne).

CHIK fever epidemics are sustained by human-mosquito-human transmission. The word "chikungunya" is thought to derive from description in local dialect of the contorted posture of patients afflicted with the severe joint pain associated with this disease. The main virus reservoirs are monkeys, but other species can also be affected, including humans.

Pathophysiology

Human epithelial and endothelial cells, primarily fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

s and monocyte-derived macrophages, are susceptible to infection. Lymphoid and monocytoid cells, primary lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

s and monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...

s and monocyte-derived dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s are not susceptible to infection. Viral entry occurs through pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

-dependent endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

. Infection is cytopathic and associated with the induction of apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 in the infected cell.

Infection is highly sensitive to the antiviral activity of type I and II interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

.

Prevention

The most effective means of prevention are protection against contact with the disease-carrying mosquitoes and mosquito control
Mosquito control
Mosquito control manages the population of mosquitoes to reduce their damage to human health, economies, and enjoyment. Mosquito control is a vital public-health practice throughout the world and especially in the tropics because mosquitoes spread many diseases, such as malaria.Mosquito-control...

. These include using insect repellent
Insect repellent
An insect repellent is a substance applied to skin, clothing, or other surfaces which discourages insects from landing or climbing on that surface. There are also insect repellent products available based on sound production, particularly ultrasound...

s with substances like DEET
DEET
N,N-Diethyl-meta-toluamide, abbreviated DEET, is a slightly yellow oil. It is the most common active ingredient in insect repellents...

 (N,N-Diethyl-meta-toluamide; also known as N,N'-Diethyl-3-methylbenzamide or NNDB), icaridin
Icaridin
Icaridin, also known as picaridine, KBR 3023, under the INCI name hydroxyethyl isobutyl piperidine carboxylate, and the trade names Bayrepel and Saltidin, is an insect repellent...

 (also known as picaridin and KBR3023), PMD (p-menthane-3,8-diol
P-menthane-3,8-diol
p-Menthane-3,8-diol, also known as para-menthane-3,8-diol, PMD, or Menthoglycol, is an active ingredient used in insect repellents. It smells similar to menthol and acts as a coolant. PMD is found in very small quantities in the essential oil within leaves of the Eucalyptus citriodora tree...

, a substance derived from the lemon eucalyptus tree), or IR3535. Wearing bite-proof long sleeves and trousers (pants) also offers protection. In addition, garments can be treated with pyrethroids, a class of insecticides that often has repellent properties. Vaporized pyrethroids (for example in mosquito coils) are also insect repellents. Securing screens on windows and doors will help to keep mosquitoes out of the house. In the case of the day-active Aedes aegypti
Aedes aegypti
The yellow fever mosquito, Aedes aegypti is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking in the form of a lyre on the thorax...

and Aedes albopictus, however, this will have only a limited effect, since many contacts between the vector and the host occur outside.

Treatment

There are no specific treatments for Chikungunya. There is no vaccine currently available. A Phase II
Phase II
Phase II may refer to:* Phase II clinical trial* Drug metabolism Phase II* Star Trek: Phase II, a planned Star Trek television series that eventually evolved into Star Trek: The Motion Picture...

 vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

 trial, sponsored by the US Government and published in the American Journal of Tropical Medicine and Hygiene in 2000, used a live, attenuated virus
Attenuated virus
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable . Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus .-Examples:Examples of...

, developing viral resistance in 98% of those tested after 28 days and 85% still showed resistance after one year.

A serological
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

 test for Chikungunya is available from the University of Malaya
University of Malaya
The University of Malaya is located on a campus near the centre of Kuala Lumpur, and is the oldest university in Malaysia. It was founded in 1905 as a public-funded tertiary institution...

 in Kuala Lumpur
Kuala Lumpur
Kuala Lumpur is the capital and the second largest city in Malaysia by population. The city proper, making up an area of , has a population of 1.4 million as of 2010. Greater Kuala Lumpur, also known as the Klang Valley, is an urban agglomeration of 7.2 million...

, icul.

Chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...

 is gaining ground as a possible treatment for the symptoms associated with Chikungunya, and as an anti-inflammatory agent to combat the arthritis associated with Chikungunya virus. A University of Malaya
University of Malaya
The University of Malaya is located on a campus near the centre of Kuala Lumpur, and is the oldest university in Malaysia. It was founded in 1905 as a public-funded tertiary institution...

 study found that for arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

-like symptoms that are not relieved by aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

 and non-steroidal anti-inflammatory drugs (NSAID), chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...

 phosphate (250 mg/day) has given promising results. Unpublished studies in cell culture and monkeys show no effect of chloroquine treatment on reduction of chikungunya disease. The fact sheet on Chikungunya advises against using aspirin, ibuprofen, naproxen and other NSAIDs that are recommended for arthritic pain and fever.

Vaccine development

A virus-like particle based vaccine has protected monkeys from Chikungunya virus infection, and passive immunization from these monkeys protected immunodeficient mice against exposure to a dose of virus that would otherwise be lethal, demonstrating that the humoral response was highly protective.

A DNA vaccine
DNA vaccination
DNA vaccination is a technique for protecting an organism against disease by injecting it with genetically engineered DNA to produce an immunological response. Nucleic acid vaccines are still experimental, and have been applied to a number of viral, bacterial and parasitic models of disease, as...

 candidate is also being tested. The vaccine cassette was designed based on CHIKV Capsid and Envelope specific consensus sequences with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. These constructs induced humoral and cellular immune responses in mice.

Passive immunity

Antibodies isolated from patients recovering from Chikungunya fever have been shown to protect mice from infection.

Prognosis

Recovery from the disease varies by age. Younger patients recover within 5 to 15 days; middle-aged patients recover in 1 to 2.5 months. Recovery is longer for the elderly. The severity of the disease as well as its duration is less in younger patients and pregnant women. In pregnant women, no untoward effects are noticed after the infection.

Ocular inflammation from Chikungunya may present as iridocyclitis
Iridocyclitis
Iridocyclitis, a type of anterior uveitis, is a condition in which the uvea of the eye is inflamed.Iridocyclitis isInflammation of the iris and the ciliary body.- Symptoms :Symptoms include:* Photophobia* Redness* Watering of the eyes* Lacrimation...

, and have retinal lesions as well.

Pedal oedema (swelling of legs) is observed in many patients, the cause of which remains obscure as it is not related to any cardiovascular, renal or hepatic abnormalities.

Epidemiology

Chikungunya virus is an alphavirus
Alphavirus
In biology and immunology, an alphavirus belongs to the group IV Togaviridae family of viruses, according to the system of classification based on viral genome composition introduced by David Baltimore in 1971. Alphaviruses, like all other group IV viruses have a positive sense single stranded RNA...

 closely related to the O'nyong'nyong virus
O'nyong'nyong virus
The O'nyong'nyong virus or O'nyong-nyong virus is a virus first isolated by the Uganda Virus Research Institute in Entebbe, Uganda in 1959. It is a togavirus , genus Alphavirus and is closely related to the Chikungunya and Igbo Ora viruses. The name comes from the Nilotic language of Uganda and...

, the Ross River virus
Ross River virus
Ross River virus 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 debilitating tropical disease known as Ross River fever, previously termed "epidemic...

 in Australia, and the viruses that cause eastern equine encephalitis and western equine encephalitis.

Three genotypes of this virus have been described: West African, East/Central/South African and Asian genotypes.

Chikungunya is generally spread through bites from Aedes aegypti
Aedes aegypti
The yellow fever mosquito, Aedes aegypti is a mosquito that can spread the dengue fever, Chikungunya and yellow fever viruses, and other diseases. The mosquito can be recognized by white markings on legs and a marking in the form of a lyre on the thorax...

mosquitoes, but recent research by the Pasteur Institute
Pasteur Institute
The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax...

 in Paris has suggested that Chikungunya virus strains in the 2005-2006 Reunion Island outbreak incurred a mutation that facilitated transmission by Aedes albopictus
Asian tiger mosquito
The Asian tiger mosquito or forest day mosquito, Aedes albopictus , from the mosquito family, is characterized by its black and white striped legs, and small black and white striped body...

 (Tiger mosquito). Concurrent studies by arbovirologists at the University of Texas Medical Branch in Galveston, Texas, confirmed definitively that enhanced chikungunya virus infection of Aedes albopictus was caused by a point mutation in one of the viral envelope genes (E1). Enhanced transmission of chikungunya virus by Aedes albopictus could mean an increased risk for chikungunya outbreaks in other areas where the Asian tiger mosquito is present. A recent epidemic in Italy was likely perpetuated by Aedes albopictus.

In Africa, chikungunya is spread via a sylvatic cycle
Sylvatic cycle
The sylvatic cycle, also enzootic or sylvatic transmission cycle, is a portion of the natural transmission cycle of a pathogen. The sylvatic cycle is the fraction of the pathogen population's lifespan spent cycling between wild animals and vectors. Humans are usually an incidental or dead-end host,...

 in which the virus largely resides in other primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...

s in between human outbreaks.

On 28 May 2009 in Changwat Trang
Trang Province
Trang is one of the southern provinces of Thailand, at the western shore of the Malay Peninsula to the Andaman Sea. Neighboring provinces are Krabi, Nakhon Si Thammarat, Phatthalung and Satun....

 of Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...

 where the virus is endemic, the provincial hospital decided to deliver by Caesarean section
Caesarean section
A Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...

 a male baby from his Chikungunya-infected mother—Khwanruethai Sutmueang, 28, a Trang native—in order to prevent mother-fetus virus transmission. However, after delivering the baby, the physicians discovered that the baby was infected with Chikungunya virus, and put him into intensive care because the infection had left the baby unable to breathe by himself or to drink milk. The physicians presumed that Chikungunya virus might be able to be transmitted from a mother to her foetus; however, there is no laboratory confirmation for this presumption.

History

The name is derived from the Makonde
Makonde
The Makonde are an ethnic group in southeast Tanzania and northern Mozambique. The Makonde developed their culture on the Mueda Plateau in Mozambique. At present they live throughout Tanzania and Mozambique and have a small presence in Kenya...

 word meaning "that which bends up" in reference to the stooped posture
Human position
Human positions refers to the different positions that the human body can take.There are several synonyms that refer to the human position, often used interchangeably, but having specific flavors....

 developed as a result of the arthritic
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

 symptoms of the 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, along the border between Mozambique
Mozambique
Mozambique, officially the Republic of Mozambique , is a country in southeastern Africa bordered by the Indian Ocean to the east, Tanzania to the north, Malawi and Zambia to the northwest, Zimbabwe to the west and Swaziland and South Africa to the southwest...

 and Tanganyika
Tanganyika
Tanganyika , later formally the Republic of Tanganyika, was a sovereign state in East Africa from 1961 to 1964. It was situated between the Indian Ocean and the African Great Lakes of Lake Victoria, Lake Malawi and Lake Tanganyika...

 (the mainland part of modern day Tanzania
Tanzania
The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...

).

According to the initial 1955 report about the epidemiology
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...

 of the disease, the term 'chikungunya' is derived from the Makonde root verb kungunyala, meaning to dry up or become contorted. In concurrent research, Robinson glossed the Makonde term more specifically as "that which bends up." Subsequent authors apparently overlooked the references to the Makonde language and assumed that the term derived from Swahili
Swahili language
Swahili or Kiswahili is a Bantu language spoken by various ethnic groups that inhabit several large stretches of the Mozambique Channel coastline from northern Kenya to northern Mozambique, including the Comoro Islands. It is also spoken by ethnic minority groups in Somalia...

, the lingua franca
Lingua franca
A lingua franca is a language systematically used to make communication possible between people not sharing a mother tongue, in particular when it is a third language, distinct from both mother tongues.-Characteristics:"Lingua franca" is a functionally defined term, independent of the linguistic...

 of the region. The erroneous attribution of the term as a Swahili word has been repeated in numerous print sources. Many other erroneous spellings and forms of the term are in common use including "Chicken guinea", "Chicken gunaya," and "Chickengunya".

Since its discovery in Tanganyika
Tanganyika
Tanganyika , later formally the Republic of Tanganyika, was a sovereign state in East Africa from 1961 to 1964. It was situated between the Indian Ocean and the African Great Lakes of Lake Victoria, Lake Malawi and Lake Tanganyika...

, Africa, in 1952, chikungunya virus outbreaks have occurred occasionally in Africa, South Asia, and Southeast Asia, but recent outbreaks have spread the disease over a wider range.

The first recorded outbreak of this disease may have in 1779.

Use as a biological weapon

Chikungunya was one of more than a dozen agents that the United States researched as potential biological weapons before the nation suspended its biological weapons program.

See also

  • Chikungunya outbreaks: outbreaks of the disease, 2004 to present.
  • DEET
    DEET
    N,N-Diethyl-meta-toluamide, abbreviated DEET, is a slightly yellow oil. It is the most common active ingredient in insect repellents...

  • O'nyong'nyong virus
    O'nyong'nyong virus
    The O'nyong'nyong virus or O'nyong-nyong virus is a virus first isolated by the Uganda Virus Research Institute in Entebbe, Uganda in 1959. It is a togavirus , genus Alphavirus and is closely related to the Chikungunya and Igbo Ora viruses. The name comes from the Nilotic language of Uganda and...

    : a similar virus.
  • Vector (epidemology)
  • Climate change, industry and society
    Climate change, industry and society
    This article is about climate change, industry and society.-Vulnerability:The ability to predict how climate change may affect industry, settlement and society is limited by uncertainites about climate change and future developments in social and economic systems...


External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK