Chikungunya

Chikungunya coyچچ
Classification and external resources
ICD-10	A92.0
ICD-9	065.4, 066.3
DiseasesDB	32213
MeSH	D018354

Chikungunya virus
Virus classification
Group:	Group IV ((+)ssRNA)
Family:	Togaviridae
Genus:	Alphavirus
Species:	Chikungunya virus

Chikungunya (in the Makonde language "that which bends up") virus (CHIKV) is an insect-borne virus, of the genus Alphavirus, that is transmitted to humans by virus-carrying Aedes mosquitoes.^[1] There have been recent breakouts of CHIKV associated with severe illness. CHIKV infection causes an illness with symptoms similar to dengue fever, with an acute febrile phase of the illness lasting only two to five days, followed by a prolonged arthralgic 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.^[2][3]

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 rash of the trunk and occasionally the limbs, and arthralgia or arthritis affecting multiple joints.^[4] Other nonspecific symptoms can include headache, conjunctivitis, and slight photophobia. 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 for about 5 to 7 days.^[4] Patients have complained of joint pains for much longer time periods; some as long as 2 years, depending on their age.^[5][6]

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.^[7] 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 genes from whole blood. Results can be determined in 1–2 days.^[7]
• 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 2–3 days and false positives can occur with infection via other related viruses such as O'nyong'nyong virus and Semliki Forest Virus.^[7]

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 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.^[8] The main virus reservoirs are monkeys, but other species can also be affected, including humans.^[9]

Pathophysiology

Human epithelial and endothelial cells, primarily fibroblasts and monocyte-derived macrophages, are susceptible to infection. Lymphoid and monocytoid cells, primary lymphocytes and monocytes and monocyte-derived dendritic cells are not susceptible to infection. Viral entry occurs through pH-dependent endocytosis. Infection is cytopathic and associated with the induction of apoptosis in the infected cell.

Infection is highly sensitive to the antiviral activity of type I and II interferon.

Prevention

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 like 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 (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 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 vaccine trial, sponsored by the US Government and published in the American Journal of Tropical Medicine and Hygiene in 2000, used a live, attenuated virus, developing viral resistance in 98% of those tested after 28 days and 85% still showed resistance after one year.^[10]

A serological test for Chikungunya is available from the University of Malaya in Kuala Lumpur, icul.

Chloroquine 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 study found that for arthritis-like symptoms that are not relieved by aspirin and non-steroidal anti-inflammatory drugs (NSAID), chloroquine phosphate (250 mg/day) has given promising results.^[11] Unpublished studies in cell culture and monkeys show no effect of chloroquine treatment on reduction of chikungunya disease. The fact sheet^[9] 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.^[12]

A DNA vaccine 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.^[13]

Passive immunity

Antibodies isolated from patients recovering from Chikungunya fever have been shown to protect mice from infection.^[14]

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, and have retinal lesions as well.^[15]

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 closely related to the O'nyong'nyong virus,^[16] the Ross River virus in Australia, and the viruses that cause eastern equine encephalitis and western equine encephalitis.^[17]

Three genotypes of this virus have been described: West African, East/Central/South African and Asian genotypes.^[18]

The Aedes aegypti mosquito biting a person.

Chikungunya is generally spread through bites from Aedes aegypti mosquitoes, but recent research by the Pasteur Institute in Paris has suggested that Chikungunya virus strains in the 2005-2006 Reunion Island outbreak incurred a mutation that facilitated transmission by Aedes albopictus (Tiger mosquito).^[19] 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).^[20][21] 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.^[22]

In Africa, chikungunya is spread via a sylvatic cycle in which the virus largely resides in other primates in between human outbreaks.^[17]

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—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.^[23]

History

The name is derived from the Makonde word meaning "that which bends up" in reference to the stooped posture developed as a result of the arthritic symptoms of the disease. The disease was first described by Marion Robinson^[24] and W.H.R. Lumsden^[25] 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 that 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 other erroneous spellings and forms of the term are in common use including "Chicken guinea", "Chicken gunaya," and "Chickengunya".^{[citation needed]}

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.

The first recorded outbreak of this disease may have in 1779.^[26]

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.^[27]

See also

• Chikungunya outbreaks: outbreaks of the disease, 2004 to present.
• DEET
• O'nyong'nyong virus: a similar virus.
• Vector (epidemology)
• Climate change, industry and society

References

1. ^ Lahariya C, Pradhan SK (December 2006). "Emergence of chikungunya virus in Indian subcontinent after 32 years: a review" (PDF). J Vect Borne Dis 43 (4): 151–60. http://www.mrcindia.org/journal/issues/434151.PDF. 
2. ^ 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. 
3. ^ 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 (June 2007). "Characterization of reemerging chikungunya virus". PLoS Pathog. 3 (6): e89. doi:10.1371/journal.ppat.0030089. PMC 1904475. PMID 17604450. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1904475. 
4. ^ ^{a b} 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. PMID 18227590. http://www.ijmm.org/article.asp?issn=0255-0857;year=2008;volume=26;issue=1;spage=5;epage=12;aulast=Chhabra. 
5. ^ Simon F, Parola P, Grandadam M, Fourcade S, Oliver M, Brouqui P, Hance P, Kraemer P, Ali Mohamed A, de Lamballerie X, Charrel R, Tolou H (May 2007). "Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases". Medicine (Baltimore) 86 (3): 123–37. doi:10.1097/MD/0b013e31806010a5. PMID 17505252. 
6. ^ Taubitz W, Cramer JP, Kapaun A, Pfeffer M, Drosten C, Dobler G, Burchard GD, Löscher T (July 2007). "Chikungunya fever in travelers: clinical presentation and course". Clin. Infect. Dis. 45 (1): e1–4. doi:10.1086/518701. PMID 17554689. 
7. ^ ^{a b c} "WHO — Laboratory Diagnosis of Chikungunya Fevers". http://www.searo.who.int/EN/Section10/Section2246_12902.htm. Retrieved 2008-07-11. 
8. ^ Centers for Disease Control and Prevention (CDC) (September 29, 2006). "Chikungunya fever diagnosed among international travelers—United States, 2005–2006". MMWR Morb. Mortal. Wkly. Rep. 55 (38): 1040–2. PMID 17008866. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5538a2.htm. 
9. ^ ^{a b} "Chikungunya—Fact sheet". European Centre for Disease Prevention and Control. 2008-01-23. http://ecdc.europa.eu/en/Health_Topics/Chikungunya_Fever/facts.aspx. Retrieved 2008-03-25. ^{[dead link]}
10. ^ 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. http://www.ajtmh.org/cgi/reprint/62/6/681. 
11. ^ Alphaviruses
12. ^ Akahata W, Yang ZY, Andersen H, et al. (March 2010). "A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection". Nat. Med. 16 (3): 334–8. doi:10.1038/nm.2105. PMC 2834826. PMID 20111039. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2834826. 
13. ^ Muthumani K, Lankaraman KM, Laddy DJ, et al. (September 2008). "Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus". Vaccine 26 (40): 5128–34. doi:10.1016/j.vaccine.2008.03.060. PMC 2582145. PMID 18471943. http://linkinghub.elsevier.com/retrieve/pii/S0264-410X(08)00341-1. 
14. ^ Couderc T, Khandoudi N, Grandadam M, et al. (2009). "Prophylaxis and therapy for Chikungunya virus infection". J Infect Dis 200 (4): 516–523. doi:10.1086/600381. PMID 19572805. http://www.journals.uchicago.edu/doi/full/10.1086/600381. 
15. ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0161-6420(07)00488-5. 
16. ^ Vanlandingham DL, Hong C, Klingler K, Tsetsarkin K, McElroy KL, Powers AM, Lehane MJ, Higgs S (2005). "Differential infectivities of o'nyong-nyong and chikungunya virus isolates in Anopheles gambiae and Aedes aegypti mosquitoes". Am J Trop Med Hyg 72 (5): 616–21. PMID 15891138. 
17. ^ ^{a b} Martin Enserink (2007). "Chikungunya: No Longer a Third World Disease". Science 318 (5858): 1860–1. doi:10.1126/science.318.5858.1860. PMID 18096785. 
18. ^ Powers AM, Brault AC, Tesh RB, Weaver SC (2000) Re-emergence of Chikungunya and O'nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships. J Gen Virol 81(2):471-479
19. ^ Martin E (2007). "EPIDEMIOLOGY: Tropical Disease Follows Mosquitoes to Europe". Science 317 (5844): 1485. doi:10.1126/science.317.5844.1485a. PMID 17872417. 
20. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2134949. 
21. ^ ProMED-mail (2007) Chikungunya virus: genetic change. Archive Number 20071209.3973
22. ^ European Centers for Disease Control Report Chikungunya in Italy.
23. ^ T Rath (2009). Trang hospital found Chikungunya transmitted from a mother to her foetus, 28 May 2009. (Accessed: 29 May 2009).
24. ^ 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. 
25. ^ 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. 
26. ^ Carey DE (July 1971). "Chikungunya and dengue: a case of mistaken identity?". J Hist Med Allied Sci 26 (3): 243–62. PMID 4938938. http://jhmas.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=4938938. 
27. ^ "Chemical and Biological Weapons: Possession and Programs Past and Present", James Martin Center for Nonproliferation Studies, Middlebury College, April 9, 2002, accessed November 14, 2008.

Further reading

• 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. 
• "Chikungunya — Fact sheet". European Centre for Disease Prevention and Control. 2008-01-23. http://www.ecdc.europa.eu/en/Health_topics/Chikungunya_Fever/. Retrieved 2008-03-19. ^{[dead link]}

External links

• WHO site on disease outbreak news
• Chikungunya and Pregnancy
• Chikungunya Infection in India and Vector Control
• 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. http://dx.plos.org/10.1371/journal.pmed.0030263. 
• Chikungunya, a debilitating illness From Reuters Alertnet
• Mosquito-borne African virus a new threat to West Update on increasing threat, from Reuters
• Virus Pathogen Database and Analysis Resource (ViPR): Togaviridae