|Classification and external resources|
Rash from chikungunya on the right foot
Chikungunya (English pronunciation: /ˌtʃɪkənˈgʊɲə/ CHI-kən-GUUN-yə; Makonde for "that which bends up") is an infection caused by the Chikungunya virus. It causes an illness with an acute febrile phase lasting two to five days, followed by a longer period of joint pains in the extremities; this pain may persist for years in some cases.
The disease is transmitted similarly to dengue fever to humans by virus-carrying Aedes mosquitoes. Specifically, two species of mosquitoes, A. albopictus and A. aegypti are extrinsic hosts (vectors) of chikungunya virus. The strain of chikungunya spreading to the US from the Caribbean is most easily spread by A. aegypti. Concern exists that this strain of chikungunya could mutate to make the A. albopictus vector more efficient. If this mutation were to occur, chikungunya would be more of a public health concern to the US. The A. albopictus or Asian tiger mosquito is more widespread in the US and is more aggressive than the A. aegypti. It is known that monkeys, apes, and rodents act as a reservoir for the virus. Having rodents as a viral reservoir for chikungunya differs from that of dengue which has only humans and nonhuman primates as hosts.
The best means of prevention is overall mosquito control and the avoidance of bites by any infected mosquitoes. No specific treatment is known, but medications can be used to reduce symptoms. Rest and fluids may also be useful.
Signs and symptoms
The incubation period of chikungunya disease ranges from 2 to 12 days, typically two to three. The majority of those infected will develop symptoms. Symptoms include a fever up to 40 °C (104 °F), petechial or maculopapular rash of the trunk and occasionally the limbs, and arthralgia or arthritis affecting multiple joints. Other nonspecific symptoms can include headache, nausea, vomiting, conjunctivitis, slight photophobia, and partial loss of taste. Ocular inflammation from chikungunya may present as iridocyclitis, or uveitis. Retinal lesions may also occur. Swelling of legs is observed in many people, the cause of which remains obscure as it is not related to any cardiovascular, renal, or hepatic abnormalities.
Typically, the fever lasts for two days and then ends abruptly. However, other symptoms, namely joint pain, intense headache, insomnia and an extreme degree of prostration, last for a variable period, usually about five to seven days. People have complained of joint pains for much longer time periods, some as long as two years, depending on their age. Recovery from the disease varies by age. Younger people recover within five to 15 days; middle-aged people recover in 1.0 to 2.5 months. Recovery is longer for the elderly. The severity of the disease, as well as its duration, is less in younger people and pregnant women. In pregnant women, no untoward effects are noticed after the infection.
Observations during recent epidemics have suggested chikungunya may cause long-term symptoms following acute infection. During the La Reunion outbreak in 2006, more than 50% of subjects over the age of 45 reported long-term musculoskeletal pain with up to 60% of people reporting prolonged arthralgia three years following initial infection. A study of imported cases in France reported that 59% of people still suffered from arthralgia two years after acute infection. Following a local epidemic of chikungunya in Italy, 66% of people reported muscles pains, joint pains, or asthenia at one year after acute infection. Long-term symptoms are not an entirely new observation; long-term arthritis was observed following an outbreak in 1979. Common predictors of prolonged symptoms are increased age and prior rheumatological disease. The cause of these chronic symptoms is currently not fully known. Markers of autoimmune or rheumatoid disease have not been found in people reporting chronic symptoms. However, some evidence from humans and animal models suggests chikungunya may be able to establish chronic infections within the host. Viral antigen was detected in a muscle biopsy of a people suffering a recurrent episode of disease three months after initial onset. Additionally, viral antigen and RNA were found in synovial macrophages of a person during a relapse of musculoskeletal disease 18 months after initial infection. Several animal models have also suggested chikungunya virus may establish persistent infections. In a mouse model, viral RNA was detected specifically in joint-associated tissue for at least 16 weeks after inoculation, and was associated with chronic synovitis. Similarly, another study reported detection of a viral reporter gene in joint tissue of mice for weeks after inoculation. In a nonhuman primate model, chikungunya virus was found to persist in the spleen for at least six weeks.
|Cryoelectron microscopy reconstruction of chikungunya virus. From EMDB entry |
|Group:||Group IV ((+)ssRNA)|
Chikungunya virus is an alphavirus with a positive-sense single-stranded RNA 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. In the United States, it is classified as a category C priority pathogen and work requires biosafety level III precautions.
Human epithelial and endothelial cells, primary fibroblasts, and monocyte-derived macrophages are permissive for chikungunya virus in vitro, and viral replication is highly cytopathic, but susceptible to type-I and -II interferon. In vivo, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells, and myofibers.
Chikungunya is generally spread through bites from A. aegypti mosquitoes, but recent 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).
Chikungunya virus infection of A. albopictus was caused by a point mutation in one of the viral envelope genes (E1). 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 recent epidemic in Italy was likely perpetuated by A. albopictus. In Africa, chikungunya is spread by a sylvatic cycle in which the virus largely resides in other primates between human outbreaks.
Upon infection with chikungunya, the host's fibroblasts produce type-1 (alpha and beta) interferon. Mice that lack the interferon alpha receptor die in two to three days upon being exposed to 102 chikungunya PFUs, while wild-type mice survive even when exposed to as many as 106 PFUs of the virus. At the same time, mice that are partially type-1 deficient (IFN α/β +/−) are mildly affected and experience symptoms such as muscle weakness and lethargy. Partidos et al. 2011 saw similar results with the live attenuated strain CHIKV181/25. However, rather than dying, the type-1 interferon-deficient (IFN α/β −/−) mice were temporarily disabled and the partially type-1 interferon-deficient mice did not have any problems.
Several studies have attempted to find the upstream components of the type-1 interferon pathway involved in the host's response to chikungunya infection. So far, no one knows the chikungunya-specific pathogen associated molecular pattern. Nonetheless, IPS-1—also known as Cardif, MAVS, and VISA—has been found to be an important factor. In 2011, White et al. found that interfering with IPS-1 decreased the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of IFN-β. Other studies have found that IRF3 and IRF7 are important in an age-dependent manner. Adult mice that lack both of these regulatory factors die upon infection with chikungunya. Neonates, on the other hand, succumb to the virus if they are deficient in one of these factors.
Chikungunya counters the type-I interferon response by producing NS2, a nonstructural protein that degrades Rpb and turns off the host cell's ability to transcribe DNA. NS2 interferes with the JAK-STAT signaling pathway and prevents STAT from becoming phosphorylated.
Common laboratory tests for chikungunya include RT-PCR, virus isolation, and serological tests.
- 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. 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. Results can be determined in one to two days.
- Serological diagnosis requires a larger amount of blood than the other methods, and uses an ELISA assay to measure chikungunya-specific IgM levels. Results require two to three days, and false positives can occur with infection via other related viruses, such as o'nyong'nyong virus and Semliki Forest virus.
The differential diagnosis may include infection with other mosquito-borne viruses, such as dengue and influenza. Chronic recurrent polyarthralgia occurs in at least 20% of chikungunya patients one year after infection, whereas such symptoms are uncommon in dengue.
The most effective means of prevention are protection against contact with the disease-carrying mosquitoes and mosquito control. These include using insect repellents with substances such as DEET (N,N-diethyl-meta-toluamide; also known as N,N'-diethyl-3-methylbenzamide or NNDB), icaridin (also known as picaridin and KBR3023), PMD (p-menthane-3,8-diol, a substance derived from the lemon eucalyptus tree), or IR3535. Wearing bite-proof long sleeves and trousers 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 A. aegypti and A. albopictus, however, this will have only a limited effect, since many contacts between the mosquitoes and humans occur outside.
Currently, no approved vaccines are available. A phase-II vaccine trial used a live, attenuated virus, 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, but have so far not reached clinical trials. In August 2014 it was revealed researchers at the National Institute of Allergy and Infectious Diseases were testing an experimental vaccine.
Currently, no specific treatment is available. Attempts to relieve the symptoms include the use of NSAIDs such as naproxen or paracetamol (acetaminophen) and fluids. Aspirin is not recommended.
In those who have more than two weeks of arthritis, ribavirin may be useful. The effect of chloroquine is not clear. It does not appear to help acute disease, but tentative evidence indicates it might help those with chronic arthritis. Steroids do not appear useful, either.
Three genotypes of this virus have been described: West African, East/Central/South African, and Asian genotypes. Explosive epidemics in Indian Ocean in 2005 and Pacific Islands in 2011, as well as now in the Americas, continue to change the distribution of genotypes, like the 5 serotypes of dengue, an entry of a new genotype into a previously infected area causes new epidemics.
On 28 May 2009 in Changwat Trang of Thailand, where the virus is endemic, the provincial hospital decided to deliver by Caesarean section a male baby from his chikungunya-infected mother, Khwanruethai Sutmueang, 28, a Trang native, to prevent mother-fetus virus transmission. However, after delivering the baby, the physicians discovered the baby was already infected with the 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 the virus might be able to be transmitted from a mother to her fetus, but without laboratory confirmation.
In December 2013, chikungunya was confirmed on the Caribbean island of St. Martin with 66 confirmed cases and suspected cases of around 181. This outbreak is the first time in the Western Hemisphere that the disease has spread to humans from a population of infected mosquitoes. By January 2014, the Public Health Agency of Canada reported that cases were confirmed on the British Virgin Islands, Saint-Barthélemy, Guadeloupe, and Martinique. In April 2014, chikungunya was also confirmed in the Dominican Republic by the Centers for Disease Control and Prevention (CDC). By the end of April, it had spread to 14 countries in all, including St. Lucia, and Haiti where an epidemic was declared.
By the end of May 2014, over ten imported cases of the virus had been reported in the United States by people traveling to Florida from areas where the virus is endemic.
On June 2014 six cases of the virus were confirmed in Brazil, two in the city of Campinas in the state of São Paulo. The six cases are Brazilian army soldiers who had recently returned from Haiti, where they were participating in the reconstruction efforts.United Nations Stabilisation Mission in Haiti. The information was officially released by Campinas municipality health secretary that has taken the appropriate actions.
On June 16, 2014, Florida had a cumulative 42 cases.
As of September 11, 2014 the number of reported cases in Puerto Rico for the year is at 1,636. http://www.elnuevodia.com/seextiendeelcontagiodelchikungunyaporlaisla-1851846.html
On June 17, 2014, Mississippi State Department of Health officials confirmed they are investigating the first potential case in a Mississippi resident who recently travelled to Caribbean nation of Haiti.
On June 19, 2014, the virus had spread to Georgia, USA.
On June 25, 2014, the Arkansas Health Department confirmed one person from the Natural State is carrying Chikungunya.
On July 17, 2014, the first chikungunya case acquired in the United States were reported in Florida by the Centers for Disease Control and Prevention. Since 2006 over 200 cases have been reported in the United States but only in people who had traveled to other countries. This is the first time the virus was passed by mosquitoes to a person on the U.S. mainland.
On September 2, 2014, the Centers for Disease Control and Prevention reported that there had been 7 confirmed cases of Chikungunya in the United States in people who had acquired the disease locally.
- Chikungunya cases development in Western Hemisphere from 2013
The word 'chikungunya' is thought to derive from a description in the Makonde language, meaning "that which bends up", of the contorted posture of people affected with the severe joint pain and arthritic 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, along the border between Mozambique and Tanganyika (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 the Makonde term more specifically as "that which bends up". Subsequent authors apparently overlooked the references to the Makonde language and assumed the term derived from Swahili, the lingua franca of the region. The erroneous attribution of the term as a Swahili word has been repeated in numerous print sources. Many erroneous spellings of the name of the disease are in common use.
Since its discovery in 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.
Society and culture
- Powers AM, Logue CH (September 2007). "Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus". J. Gen. Virol. 88 (Pt 9): 2363–77. doi:10.1099/vir.0.82858-0. PMID 17698645.
- Sourisseau M, Schilte C, Casartelli N, et al. (June 2007). "Characterization of reemerging chikungunya virus". PLoS Pathog. 3 (6): e89. doi:10.1371/journal.ppat.0030089. PMC 1904475. PMID 17604450.
- Lahariya C, Pradhan SK (December 2006). "Emergence of chikungunya virus in Indian subcontinent after 32 years: A review". J Vector Borne Dis 43 (4): 151–60. PMID 17175699.
- Staples, Erin; Fischer, Marc (4 Sep 2014). "Chikungunya Virus in the Americas — What a Vectorborne Pathogen Can Do". The New England Journal of Medicine (371): 887–889. doi:10.1056/NEJMp1407698. Retrieved 8 September 2014.
- Kuehn, B., 2014, After Chikungunya Virus Transmission Detected in United States, Health Authorities Brace for Wider Spread, news@JAMA
- Robert-Koch-Institut: Chikungunyafieber - eine Übersicht. In: Epidemiologisches Bulletin. 10. März 2006 / Nr. 10, S. 75-77, ISSN 1430-0265 (PDF; 115 kB)
- "Vector-borne viral infections" . World Health Organization. Retrieved 17 January 2011.
- Caglioti, C; Lalle, E; Castilletti, C; Carletti, F; Capobianchi, MR; Bordi, L (Jul 2013). "Chikungunya virus infection: an overview.". The new microbiologica 36 (3): 211–27. PMID 23912863.
- Fischer, M; Staples, JE; Arboviral Diseases Branch, National Center for Emerging and Zoonotic Infectious Diseases,, CDC (Jun 6, 2014). "Notes from the Field: Chikungunya Virus Spreads in the Americas - Caribbean and South America, 2013-2014.". MMWR. Morbidity and mortality weekly report 63 (22): 500–501. PMID 24898168.
- Powers, Ann. "Chikungunya". CDC. Retrieved 12 May 2014.
- Chhabra M, Mittal V, Bhattacharya D, Rana U, Lal S (2008). "Chikungunya fever: a re-emerging viral infection". Indian J Med Microbiol 26 (1): 5–12. doi:10.4103/0255-0857.38850. PMID 18227590.
- Vatsal Anand (18 March 2011). "Aftereffects of Chikungunya Fever". Retrieved 2012-06-29.
- Mahendradas P, Ranganna SK, Shetty R, et al. (February 2008). "Ocular manifestations associated with chikungunya". Ophthalmology 115 (2): 287–91. doi:10.1016/j.ophtha.2007.03.085. PMID 17631967.
- Simon F, Parola P, Grandadam M, et al. (May 2007). "Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases". Medicine 86 (3): 123–37. doi:10.1097/MD/0b013e31806010a5. PMID 17505252.
- Taubitz W, Cramer JP, Kapaun A, et al. (July 2007). "Chikungunya fever in travelers: clinical presentation and course". Clin. Infect. Dis. 45 (1): e1–4. doi:10.1086/518701. PMID 17554689.
- Gérardin, P; Fianu, A; Michault, A; Mussard, C; Boussaïd, K; Rollot, O; Grivard, P; Kassab, S; Bouquillard, E; Borgherini, G; Gaüzère, BA; Malvy, D; Bréart, G; Favier, F (Jan 9, 2013). "Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study.". Arthritis research & therapy 15 (1): R9. doi:10.1186/ar4137. PMID 23302155.
- Schilte, C; Staikowsky, F; Couderc, T; Madec, Y; Carpentier, F; Kassab, S; Albert, ML; Lecuit, M; Michault, A (2013). "Chikungunya virus-associated long-term arthralgia: a 36-month prospective longitudinal study.". PLoS neglected tropical diseases 7 (3): e2137. doi:10.1371/journal.pntd.0002137. PMID 23556021.
- Larrieu, S; Pouderoux, N; Pistone, T; Filleul, L; Receveur, MC; Sissoko, D; Ezzedine, K; Malvy, D (Jan 2010). "Factors associated with persistence of arthralgia among Chikungunya virus-infected travellers: report of 42 French cases.". Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 47 (1): 85–8. doi:10.1016/j.jcv.2009.11.014. PMID 20004145.
- Moro, ML; Grilli, E; Corvetta, A; Silvi, G; Angelini, R; Mascella, F; Miserocchi, F; Sambo, P; Finarelli, AC; Sambri, V; Gagliotti, C; Massimiliani, E; Mattivi, A; Pierro, AM; Macini, P; Study Group “Infezioni da Chikungunya in, Emilia-Romagna” (Aug 2012). "Long-term chikungunya infection clinical manifestations after an outbreak in Italy: a prognostic cohort study.". The Journal of infection 65 (2): 165–72. doi:10.1016/j.jinf.2012.04.005. PMID 22522292.
- Fourie, ED; Morrison, JG (Jul 28, 1979). "Rheumatoid arthritic syndrome after chikungunya fever.". South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 56 (4): 130–2. PMID 494034.
- Sissoko, D; Malvy, D; Ezzedine, K; Renault, P; Moscetti, F; Ledrans, M; Pierre, V (2009). "Post-epidemic Chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period.". PLoS neglected tropical diseases 3 (3): e389. doi:10.1371/journal.pntd.0000389. PMID 19274071.
- Manimunda, SP; Vijayachari, P; Uppoor, R; Sugunan, AP; Singh, SS; Rai, SK; Sudeep, AB; Muruganandam, N; Chaitanya, IK; Guruprasad, DR (Jun 2010). "Clinical progression of chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging.". Transactions of the Royal Society of Tropical Medicine and Hygiene 104 (6): 392–9. doi:10.1016/j.trstmh.2010.01.011. PMID 20171708.
- Ozden, S; Huerre, M; Riviere, JP; Coffey, LL; Afonso, PV; Mouly, V; de Monredon, J; Roger, JC; El Amrani, M; Yvin, JL; Jaffar, MC; Frenkiel, MP; Sourisseau, M; Schwartz, O; Butler-Browne, G; Desprès, P; Gessain, A; Ceccaldi, PE (Jun 13, 2007). "Human muscle satellite cells as targets of Chikungunya virus infection.". PLoS ONE 2 (6): e527. doi:10.1371/journal.pone.0000527. PMID 17565380.
- Hoarau, JJ; Jaffar Bandjee, MC; Krejbich Trotot, P; Das, T; Li-Pat-Yuen, G; Dassa, B; Denizot, M; Guichard, E; Ribera, A; Henni, T; Tallet, F; Moiton, MP; Gauzère, BA; Bruniquet, S; Jaffar Bandjee, Z; Morbidelli, P; Martigny, G; Jolivet, M; Gay, F; Grandadam, M; Tolou, H; Vieillard, V; Debré, P; Autran, B; Gasque, P (May 15, 2010). "Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response.". Journal of immunology (Baltimore, Md. : 1950) 184 (10): 5914–27. doi:10.4049/jimmunol.0900255. PMID 20404278.
- Hawman, DW; Stoermer, KA; Montgomery, SA; Pal, P; Oko, L; Diamond, MS; Morrison, TE (Dec 2013). "Chronic joint disease caused by persistent chikungunya virus infection is controlled by the adaptive immune response.". Journal of Virology 87 (24): 13878–88. doi:10.1128/JVI.02666-13. PMID 24131709.
- Teo, TH; Lum, FM; Claser, C; Lulla, V; Lulla, A; Merits, A; Rénia, L; Ng, LF (Jan 1, 2013). "A pathogenic role for CD4+ T cells during Chikungunya virus infection in mice.". Journal of immunology (Baltimore, Md. : 1950) 190 (1): 259–69. doi:10.4049/jimmunol.1202177. PMID 23209328.
- Labadie, K; Larcher, T; Joubert, C; Mannioui, A; Delache, B; Brochard, P; Guigand, L; Dubreil, L; Lebon, P; Verrier, B; de Lamballerie, X; Suhrbier, A; Cherel, Y; Le Grand, R; Roques, P (Mar 2010). "Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages.". The Journal of Clinical Investigation 120 (3): 894–906. doi:10.1172/JCI40104. PMID 20179353.
- Sun, S.; Xiang, Y.; Akahata, W.; Holdaway, H.; Pal, P.; Zhang, X.; Diamond, M. S.; Nabel, G. J.; Rossmann, M. G. (2013). "Structural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization". ELife 2: e00435. doi:10.7554/eLife.00435. PMC 3614025. PMID 23577234.
- Powers, AM; Brault, AC; Shirako, Y; Strauss, EG; Kang, W; Strauss, JH; Weaver, SC (November 2001). "Evolutionary relationships and systematics of the alphaviruses". Journal of Virology 75 (21): 10118–31. doi:10.1128/JVI.75.21.10118-10131.2001. PMC 114586. PMID 11581380.
- "NIAID Category A, B, and C Priority Pathogens". Retrieved 1 January 2014.
- "Biosafety in Microbiological and Biomedical Laboratories (BMBL) Fifth Edition". Retrieved 1 January 2014.
- Sourisseau, M; Schilte, C; Casartelli, N; Trouillet, C; Guivel-Benhassine, F; Rudnicka, D; Sol-Foulon, N; Le Roux, K; Prevost, MC; Fsihi, H; Frenkiel, MP; Blanchet, F; Afonso, PV; Ceccaldi, PE; Ozden, S; Gessain, A; Schuffenecker, I; Verhasselt, B; Zamborlini, A; Saïb, A; Rey, FA; Arenzana-Seisdedos, F; Desprès, P; Michault, A; Albert, ML; Schwartz, O (Jun 2007). "Characterization of reemerging chikungunya virus.". PLoS Pathogens 3 (6): e89. doi:10.1371/journal.ppat.0030089. PMC 1904475. PMID 17604450.
- Schilte, C; Couderc, T; Chretien, F; Sourisseau, M; Gangneux, N; Guivel-Benhassine, F; Kraxner, A; Tschopp, J; Higgs, S; Michault, A; Arenzana-Seisdedos, F; Colonna, M; Peduto, L; Schwartz, O; Lecuit, M; Albert, ML (Feb 15, 2010). "Type I IFN controls chikungunya virus via its action on nonhematopoietic cells.". The Journal of experimental medicine 207 (2): 429–42. doi:10.1084/jem.20090851. PMC 2822618. PMID 20123960.
- Rohatgi, A; Corbo, JC; Monte, K; Higgs, S; Vanlandingham, DL; Kardon, G; Lenschow, DJ (Dec 11, 2013). "Infection of myofibers contributes to the increased pathogenicity during infection with an epidemic strain of Chikungunya Virus.". Journal of Virology 88 (5): 2414–25. doi:10.1128/JVI.02716-13. PMID 24335291.
- Enserink M (December 2007). "Infectious diseases. Chikungunya: no longer a third world disease". Science 318 (5858): 1860–1. doi:10.1126/science.318.5858.1860. PMID 18096785.
- Martin E (2007). "EPIDEMIOLOGY: Tropical Disease Follows Mosquitoes to Europe". Science 317 (5844): 1485. doi:10.1126/science.317.5844.1485a. PMID 17872417.
- Tsetsarkin KA, Vanlandingham DL, McGee CE, Higgs S (2007). "A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential". PLoS Pathog 3 (12): e201. doi:10.1371/journal.ppat.0030201. PMC 2134949. PMID 18069894.
- "(2007) Chikungunya virus: genetic change. Archive Number 20071209.3973". ProMED-mail. Retrieved 2014-05-19.
- European Centers for Disease Control Report Chikungunya in Italy.[dead link]
- Schilte C, Couderc T, Chretien F, et al. (February 2010). "Type I IFN controls chikungunya virus via its action on nonhematopoietic cells". J. Exp. Med. 207 (2): 429–42. doi:10.1084/jem.20090851. PMC 2822618. PMID 20123960.
- Couderc T, Chrétien F, Schilte C, et al. (February 2008). "A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease". PLoS Pathog. 4 (2): e29. doi:10.1371/journal.ppat.0040029. PMC 2242832. PMID 18282093.
- Partidos CD, Weger J, Brewoo J, et al. (April 2011). "Probing the attenuation and protective efficacy of a candidate chikungunya virus vaccine in mice with compromised interferon (IFN) signaling". Vaccine 29 (16): 3067–73. doi:10.1016/j.vaccine.2011.01.076. PMC 3081687. PMID 21300099.
- White LK, Sali T, Alvarado D, et al. (January 2011). "Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff". J. Virol. 85 (1): 606–20. doi:10.1128/JVI.00767-10. PMC 3014158. PMID 20962078.
- Rudd PA, Wilson J, Gardner J, et al. (September 2012). "Interferon response factors 3 and 7 protect against Chikungunya virus hemorrhagic fever and shock". J. Virol. 86 (18): 9888–98. doi:10.1128/JVI.00956-12. PMC 3446587. PMID 22761364.
- Schilte C, Buckwalter MR, Laird ME, Diamond MS, Schwartz O, Albert ML (April 2012). "Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and nonhematopoietic cells during host response to Chikungunya infection". J. Immunol. 188 (7): 2967–71. doi:10.4049/jimmunol.1103185. PMID 22371392.
- Akhrymuk I, Kulemzin SV, Frolova EI (July 2012). "Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II". J. Virol. 86 (13): 7180–91. doi:10.1128/JVI.00541-12. PMC 3416352. PMID 22514352.
- Fros JJ, Liu WJ, Prow NA, et al. (October 2010). "Chikungunya virus nonstructural protein 2 inhibits type I/II interferon-stimulated JAK-STAT signaling". J. Virol. 84 (20): 10877–87. doi:10.1128/JVI.00949-10. PMC 2950581. PMID 20686047.
- "Laboratory Diagnosis of Chikungunya Fevers". World Health Organization. Archived from the original on September 8, 2012. Retrieved May 20, 2013.
- Morens DM and Fauci AS (4 September 2014). "Chikungunya at the Door — Déjà Vu All Over Again?". New England Journal of Medicine 371 (10): 885–887. doi:10.1056/NEJMp1408509. Retrieved 12 September 2014.
- Edelman R, Tacket CO, Wasserman SS, Bodison SA, Perry JG, Mangiafico JA (June 2000). "Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218". Am. J. Trop. Med. Hyg. 62 (6): 681–5. PMID 11304054.
- Gorchakov, R; Wang, E; Leal, G; Forrester, NL; Plante, K; Rossi, SL; Partidos, CD; Adams, AP; Seymour, RL; Weger, J; Borland, EM; Sherman, MB; Powers, AM; Osorio, JE; Weaver, SC (Jun 2012). "Attenuation of Chikungunya virus vaccine strain 181/clone 25 is determined by two amino acid substitutions in the E2 envelope glycoprotein.". Journal of Virology 86 (11): 6084–96. doi:10.1128/JVI.06449-11. PMID 22457519.
- Plante, K; Wang, E; Partidos, CD; Weger, J; Gorchakov, R; Tsetsarkin, K; Borland, EM; Powers, AM; Seymour, R; Stinchcomb, DT; Osorio, JE; Frolov, I; Weaver, SC (Jul 2011). "Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.". PLoS Pathogens 7 (7): e1002142. doi:10.1371/journal.ppat.1002142. PMID 21829348.
- Hallengärd, D; Kakoulidou, M; Lulla, A; Kümmerer, BM; Johansson, DX; Mutso, M; Lulla, V; Fazakerley, JK; Roques, P; Le Grand, R; Merits, A; Liljeström, P (Dec 26, 2013). "Novel attenuated Chikungunya vaccine candidates elicit protective immunity in C57BL/6 mice.". Journal of Virology 88 (5): 2858–66. doi:10.1128/JVI.03453-13. PMID 24371047.
- "Experimental chikungunya vaccine shows promise". Big News Network.com. 15 August 2014. Retrieved 15 August 2014.
- "Chikungunya—Fact sheet". European Centre for Disease Prevention and Control (ECDC). Retrieved 2013-12-17.
- Powers AM, Brault AC, Tesh RB, Weaver SC (February 2000). "Re-emergence of Chikungunya and O'nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships". J. Gen. Virol. 81 (Pt 2): 471–9. PMID 10644846.
- T Rath (2009). Trang hospital found Chikungunya transmitted from a mother to her foetus, 28 May 2009. Accessed: 29 May 2009.
- "Caribbean chikungunya outbreak grows, poses threat to US | CIDRAP". Cidrap.umn.edu. 2013-12-30. Retrieved 2014-05-06.
- "Mosquito-borne health alerts issued for St. Martin". Canadian Broadcasting Corporation.
- "Mosquito-borne chikungunya virus infects people on 5 Caribbean islands". Canadian Broadcasting Corporation. 2014-01-21. Retrieved 2014-02-01.
- "Pruebas de laboratorio confirman virus de Chikungunya en Nigua". Diario Libre.
- "Chikungunya now an epidemic in the Caribbean". Jamaica Observer. May 1, 2014. Retrieved May 2, 2014.
- "Caribbean hospitals overwhelmed with rapidly spreading virus". The Canadian Press. 2014-05-22. Retrieved 2014-05-22.
- http://www.floridahealth.gov/diseases-and-conditions/mosquito-borne-diseases/surveillance.html | accessed May 24, 2014
- "Illness Borne By Mosquitoes Reported in Polk County". The Ledger. 2014-06-23. Retrieved 2014-07-01.
- Chikungunya virus in the United States. Centers for Disease Control. September 2, 2014 http://www.cdc.gov/chikungunya/geo/united-states.html
|url=missing title (help). Retrieved 8 Sep 2014.
- Centers for Disease Control and Prevention (29 September 2006). "Chikungunya fever diagnosed among international travelers—United States, 2005–2006". MMWR Morb. Mortal. Wkly. Rep. 55 (38): 1040–2. PMID 17008866.
- Robinson MC (1955). "An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features". Trans. R. Soc. Trop. Med. Hyg. 49 (1): 28–32. doi:10.1016/0035-9203(55)90080-8. PMID 14373834.
- Lumsden WH (1955). "An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–53. II. General description and epidemiology". Trans. R. Soc. Trop. Med. Hyg. 49 (1): 33–57. doi:10.1016/0035-9203(55)90081-X. PMID 14373835.
- Carey DE (July 1971). "Chikungunya and dengue: a case of mistaken identity?". J Hist Med Allied Sci 26 (3): 243–62. doi:10.1093/jhmas/XXVI.3.243. PMID 4938938.
- Cherian SS, Walimbe AM, Jadhav SM, et al. (January 2009). "Evolutionary rates and timescale comparison of Chikungunya viruses inferred from the whole genome/E1 gene with special reference to the 2005-07 outbreak in the Indian subcontinent". Infect. Genet. Evol. 9 (1): 16–23. doi:10.1016/j.meegid.2008.09.004. PMID 18940268.
- "Chemical and Biological Weapons: Possession and Programs Past and Present", James Martin Center for Nonproliferation Studies, Middlebury College, 9 April 2002, accessed 18 June 2014.
- "Chikungunya". European Centre for Disease Prevention and Control. 23 January 2008. Retrieved May 20, 2013.
- Doucleff, Michaeleen. "Chikun-What? A New Mosquito-Borne Virus Lands In The U.S." NPR. 3 July 2014. Retrieved 4 July 2014.
- Morgan, David. "Mosquito-borne African virus a new threat to West." Reuters. 18 September 2009. Retrieved 4 July 2014.
- Powers AM, Logue CH (2007). "Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus". J Gen Virol 88 (9): 2363–77. doi:10.1099/vir.0.82858-0. PMID 17698645.
- Schuffenecker I, Iteman I, Michault A, et al. (July 2006). "Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak". PLoS Med. 3 (7): e263. doi:10.1371/journal.pmed.0030263. PMC 1463904. PMID 16700631.
- Chikungunya fact sheet — from WHO World Health Organization
- Chikungunya outbreaks — from WHO World Health Organization
- Togaviridae — from ViPR Virus Pathogen Resource
- Chikungunya in Cuba