Chikungunya

Chikungunya (in the Makonde language "that leans downward") 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 causes an illness with symptoms similar to dengue fever. CHIKV manifests itself 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 four 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, conjunctival Infection, 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 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

This has been poorly researched to date.

Human epithelial and endothelial cells, primary 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, Malaysia.

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] Research by an Italian scientist, Andrea Savarino, and his colleagues together with a French government press release in March 2006^[12] have added more credence to the claim that chloroquine might be effective in treating chikungunya. 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.

DNA vaccine

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 well as to several tumour models. DNA vaccines have a number of advantages over conventional vaccines, including the ability to induce a wider range of immune response types. A recent study supports a novel consensus-based approach to vaccine design for Chikungunya virus employing a DNA vaccine strategy. 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. Analysis of cellular immune responses, including epitope mapping, demonstrates that these constructs induces both potent and broad cellular immunity in mice. In addition, antibody ELISAs demonstrate that these synthetic immunogens are capable of inducing high titer antibodies capable of recognizing native antigen. Taken together, these results support further study of the use of consensus CHIKV antigens in a potential vaccine cocktail.^[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]

The Aedes aegypti mosquito biting human flesh.

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).^[18] 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).^[19][20] 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.^[21]

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-foetus 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.^[22]

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^[23] and W.H.R. Lumsden^[24] 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".

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.

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.^[25]

See also

• Chikungunya outbreaks: outbreaks of the disease, 2004 to present.
• DEET
• O'nyong'nyong virus: a similar virus.

Further reading

• "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. 

References

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. PMID 16700631. PMC 1463904. 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
• Information about previous outbreaks of Chikungunya