A Review Of Chikungunya

Vaccines and new drugs against chikungunya are urgently needed. Chikungunya is generally not fatal.

However, in 2005-2007, many deaths have been associated with chikungunya worldwide and still it is continuing. Currently there is no vaccine and fully satisfied drugs to treat all symptoms of chikungunya.Treatment are just symptomatic and in many cases improper use of NSAIDS leads to more complications. Every year 1000s are getting infected and many are dying. So it is high time to turn health organisation’s concentration to find a solution for this health issue.

Introduction

The word chikungunya meaning "that which bends up", which is derived from its arthritic symptoms. It is the hottest topic of discussion among public today, so is necessary to know the causes, symptoms, treatment and preventive measures of this viral fever. Usually chikungunya virus or CHIKV is spread by mosquito bites from Aedes aegypti mosquitoes, Aedes albopictus (Tiger mosquito), Aedes luteocephalus, or A. taylori.. There is no reported case of human-human transmission of CHIKV. The outbreak of infection and studies about it reveals that people living near to forest and water stores are more prone to this viral desease, since these areas provide better environment for mosquito breeding.

High fever and arthritic pain, especially severe pain on extremes is characteristic of chikungunya fever. In allopathic, treatment is based on the symptoms and no preventive drugs are available. Siddha system claims some medicines for both treatment and prevention, but is not scientifically proven. By taking proper precaution against mosquito bites by using insecticides, repellents and other measures, transmission of CHIKV can be prevented to greater extent.

What is chikungunya?

Chikungunya is a viral disease transmitted to humans by the bite of infected mosquitoes. Chikungunya virus (CHIKV) is a member of the genus Alphavirus, in the family Togaviridae^[1,2]. In India, this viral disease is spread by mosquito bites from Aedes aegypti mosquitoes,^{[3, 4, 5]}, though recent research by the Pasteur Institute in Paris claims the virus has suffered a mutation that enables it to be transmitted by Aedes albopictus (Tiger mosquito).a genetic change in position 226 of E1 in a close relative of the chikungunya virus meant that, that virus no longer needed cholesterol (which viruses normally need to infect the cells of their human and mosquito hosts) ^[6]. Because mosquitoes often do not have enough cholesterol for viruses to efficiently affect their cells, it is possible that the more recent version of the chikungunya virus (the V version) could have survived and multiplied better in mosquitoes, which in turn could have contributed to its rapid spread.^[7]CHIKV was first isolated from the blood of a febrile patient in Tanzania in 1953, and has since been identified repeatedly in west, central and southern Africa and many areas of Asia, and has been cited as the cause of numerous human epidemics in those areas since that time. The virus circulates throughout much of Africa, with transmission thought to occur mainly between mosquitoes and monkeys.

Etymology

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 ^[8] and W.H.R. Lumsden ^[9]in 1956, following an outbreak on the Makonde Plateau, along the border between Tanganyika and Mozambique, in 1952 ^[10]. Chikungunya is closely related to O'nyong'nyong virus ^{[11, 12,} ^13] which can cause human death.

Epidemiology

Chikungunya was first described in Tanzania, Africa in 1952. The first outbreak ^[14] in India was in 1963 in Calcutta. An outbreak of chikungunya was also discovered in Port Klang in Malaysia in 1999 affecting 27 people.

Impact

Chikungunya is generally not fatal. However, in 2005-till date, many deaths have been associated with chikungunya on Reunion island and a widespread outbreak in India, primarily in Tamil Nadu, Karnataka, Kerala, and Andhra Pradesh. After flood and heavy rains in Rajasthan, India in August 2006, thousands of cases were detected in Rajsamand, Bhilwara, Udaipur, and Chittorgarh districts and also in adjoining regions of Gujarat and Madhya Pradesh, and in the neighbouring country of Sri Lanka. In the southern Indian state of Kerala, 125 deaths were attributed to Chikungunya with the majority of the casualties reported in the district of Alapuzha [mainly in Cherthala Taluk]. In December 2006, an outbreak of 3,500 confirmed cases occurred in Maldives, and over 60,000 cases in Sri Lanka, with over 80 deaths. In October 2006 more than a dozen cases of Chikungunya were reported in Pakistan. ^{[15, 16]}

An analysis of the virus's ^[17] genetic code suggests that the increased severity of the 2005 - present outbreak may be due to a change in the genetic sequence, altering the virus's coat protein, which potentially allows it to multiply more easily in mosquito cells. In July 2006, a team analyzed the virus's RNA ^[18] and determined the genetic changes that have occurred in various strains of the virus and identified those genetic sequences which led to the increased virulence of recent strains. ^{[12, 19]}

Causes and transmission of CHICV

CHIKV is spread by the bite of an infected mosquito. Mosquitoes become infected when they feed from a person infected with CHIKV. Monkeys, and possibly other wild animals, may also serve as reservoirs of the virus. Infected mosquitoes can then spread the virus to other humans when they bite. In Africa, the virus is maintained through a sylvatic transmission cycle between wild primates and mosquitoes such as Aedes luteocephalus, A. furcifer, or A. taylori. ^[8] In Asia, CHIKV is transmitted from human to human mainly by A. aegypti (the yellow fever mosquito), a household container breeder and aggressive daytime biter which is attracted to humans, and, to a lesser extent, by A. albopictus (the Asian tiger mosquito) through an urban transmission cycle.

The time of greatest risk of chikungunya virus transmission from a mother to fetus appears to be during birth, if the mother acquired the disease, days before delivery and carries the virus, according to the Perinatal Network of Reunion. This network of physicians and researchers on the French island of La Reunion has published a wealth of data on chikungunya infection during pregnancy since the epidemic began in March 2005. Preliminary data showed that such a contamination is "rarely serious" and more than 90 percent of the infected newborns recovered quickly without sequelae.

According to Dr. Marc Gabriele and Dr. Alby Jean Dominique of the Perinatal Network, they have seen cases of mother-to-fetus infection which occurred between 3 and 4.5 months of pregnancy. Beyond this period of pregnancy, no infection was found. However, there is a 48 percentage risk of infection at birth if the virus is still present in the mother's blood.

The incubation period (time from infection to illness) can be 2-12 days, but is usually 3-7 days. “Silent” CHIKV infections (infections without illness) do occur; but how commonly this happens is not yet known.

CHIKV infection (whether clinical or silent) is thought to confer life-long immunity. According to the Regional Department of Health and Social Affairs of La Reunion, Immunoglobulin M [IgM], an antibody, generally appears between 4 and 7 days after the onset of clinical signs. IgM, however, does not pass through the placental barrier. The body starts producing Immunoglobulin G [IgG] around Day 15 and does pass it through the placenta and confer immunity to the fetus.

The Health and Social Affair Department mentions that such an infection may be "at the origin of miscarriages", but that they have not seen any increases in cases of birth defects associated with the illness. Fever, in general, can trigger uterine contractions, miscarriages or fetal deaths.

When the babies were infected during birth, signs of infection appeared around Day 4. More than 90 percent of the infected newborns recovered rapidly without any subsequent problems.

Detection of chikungunya virus (CHICV)

Blood test is the way to detect chikungunya virus. Conventional RT-PCR with a detection limit of 0.1PFU/ml., immunofluorescence analysis and one-step SYBR Green I-based real-time RT-PCR assay with detection limit of 10(7)-0.1PFU/ml is available .

Symptoms

CHIKV infection can cause a debilitating illness, most often characterized by fever^[20], which can reach 39°C, (102.2°F) a petechial or maculopapular rash^[10,21] usually involving the limbs and trunk and arthralgia or arthritis affecting multiple joints which can be debilitating. The symptoms could also include headache, conjunctival infection, and slight photophobia. In the present epidemic in the states of Andhra Pradesh and Tamil Nadu, India, high fever and crippling joint pain are the prevalent complaint. The fever typically lasts for two days and abruptly comes down. However, other symptoms like intense headache, insomnia and an extreme degree of prostration last for a variable period, usually for about1-10 days.However, arthralgia may persist for months or years. In some patients, minor hemorrhagic signs such as epistaxis or gingivorrhagia have also been described. Platelet count in the body decrease until the disease persists. A condition known as Nuetropenia occurs at times. It is a condition in which the antibodies destroy the nuetrophils which are important white blood cells that help fight infection. Children, pregnant women and person under stress will be prone for more serious form of the complications.

Dermatological manifestations observed in a recent outbreak of Chikungunya fever in Southern India, Western India (Surat) and Eastern India (Puri) includes the following:

Maculopapular rash
Nasal blotchy erythema
Freckle-like pigmentation over centro-facial area
Flagellate pigmentation on face and extremities
Lichenoid eruption and hyperpigmentation in photodistributed areas
Multiple aphthous-like ulcers over scrotum, crural areas and axilla.
Lympoedema in acral distribution (bilateral/unilateral)
Multiple ecchymotic spots (Children)
Vesiculobullous lesions (infants)
Subungual hemorrhage
Photo Urticaria
Acral Urticaria
Cephalgia
Lumbago
Coffee Colored Vomiting
Epistaxis
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.

Treatment

There is no specific vaccine or specific antiviral treatment for Chikungunya. Vaccine trials were carried out in 2000, but funding for the project was discontinued and there is no vaccine currently available. Chloroquine^[22] is gaining ground as a possible treatment for the symptoms associated with Chikungunya and as an antiviral agent to combat the Chikungunya virus. According to the University of Malaya, in unresolved arthritis refractory to aspirin^[23]and nonsteroidal anti-inflammatory drugs, chloroquine phosphate (250 mg/day) has given promising results. Research by Italian scientist, Andrea Savarino, and his colleagues, in addition a French government press release in March 2006 have added more credence to the claim that chloroquine may be effective in treating Chikungunya. The researches on treatment of CHIKV infection advises against usage of Aspirin. Ibuprofen, Naproxen and other non-steroidal anti-inflammatory drugs are recommended for arthritic pain and fever.

Infected persons should limit further exposure to mosquito bites, stay indoors and under a mosquito net so that they can't contribute to the transmission cycle. Further, "supportive" care with rest is indicated during the acute joint symptoms and must avoid "rubbing" and "massaging" as pressure appears to inflame the joints further. Movement and mild exercise tend to improve stiffness and morning arthralgia, but heavy exercise may exacerbate rheumatic symptoms. Arthralgia remains troublesome even after 8 months.

In siddha, for the treatment of chikungunya, antipyretic is given to reduce the temperature. Nilavembu Kudineer (Kudineer-Decoction) is one of the best antipyretic drug. Along with this decoction, Vathajura Kudineer can be given; it helps to reduce the joint pain and swelling.

According to Siddha system, these are some effective Siddha Medicines for Chikungunya^[24]

1. Santha Chandrodaya Mathirai

2. Balasanjeevi Mathirai

3. Brahmananda Bhairava Mathirai

4. Ashta Bhairava Mathirai

5. Vasantha Kusumaraga Mathirai

Any one or two of the above drugs can be given according to the severity of the disease. And the dose is two tablets each, 3 times a day with one or both of the above Kudineer (decoctions). The patient must administer complete rest and is advised to take healthy food. Sour and cold food substances must be avoided.

Prevention

The best way to avoid CHIKV infection is to prevent mosquito bites. There is no vaccine or preventive drug in allopathic. Prevention tips are similar to those for dengue or West Nile virus and these are as follows.

1. Use insect repellent containing a DEET^[25] (N,N-diethyl-3-methylbenzamide, N,N-diethyl-m-toluamide) or another EPA-registered active ingredient on exposed skin

Always follow the directions on the package of repellent. Length of protection from mosquito bites varies with the amount of active ingredient, ambient temperature, amount of physical activity/perspiration, any water exposure, abrasive removal, and other factors. For long duration protection use a long lasting (micro-encapsulated) formula and re-apply as necessary, according to label instructions.

EPA recommends the following precautions when using insect repellents:

Apply repellents only to exposed skin and/or clothing (as directed on the product label.) Do not use repellents under clothing.
Never use repellents over cuts, wounds or irritated skin.
Do not apply to eyes or mouth, and apply sparingly around ears. When using sprays, do not spray directly on face. Spray on hands first and then apply to face.
Do not allow children to handle the product. When using on children, apply to your own hands first and then put it on the child. You may not want to apply to children’s hands.
Use just enough repellent to cover exposed skin and/or clothing. Heavy application and saturation are generally unnecessary for effectiveness. If biting insects do not respond to a thin film of repellent, then apply a bit more.
After returning indoors, wash treated skin with soap and water or bathe. This is particularly important when repellents are used repeatedly in a day or on consecutive days. Also, wash treated clothing before wearing it again. (This precaution may vary with different repellents).
If anybody gets a rash or other bad reaction from an insect repellent, stop using the repellent, wash the repellent off with mild soap and water, and call a local poison control center for further guidance. If goes to a doctor because of the repellent, take the repellent along with to show the doctor.

Note that the label for products containing oil of lemon eucalyptus specifies that they should not to be used on children under the age of three years. DEET-based repellents applied according to label instructions may be used along with a separate sunscreen. No data are available at this time regarding the use of other active repellent ingredients in combination with a sunscreen

2. Certain products which contain permethrin are recommended for use on clothing, shoes, bed nets, and camping gear, and are registered with EPA for this use. Permethrin is highly effective as an insecticide and as a repellent. Permethrin-treated clothing repels and kills ticks, mosquitoes, and other arthropods and retains this effect after repeated laundering. The permethrin insecticide should be reapplied by following the label instructions. Some commercial products pretreated with permethrin are available.

3. Wear long sleeves and pants (ideally treat clothes with permethrin or another repellent).

4. Have secure screens on windows and doors to keep mosquitoes out.

5. Get rid of mosquito breeding sites by emptying standing water from flower pots, buckets and barrels. Change the water in pet dishes and replace the water in bird baths weekly. Drill holes in tire swings so water drains out. Keep children's wading pools empty and on their sides when they aren't being used.

6. Additionally, a person with chikungunya fever should limit their exposure to mosquito bites in order to avoid further spreading of infection.

In siddha, Balasanjeevi Tablet is given in the water boiled with cumin seeds (jeeragam) and thulasi regularly, to act as a best preventive medicine against Chikungunya.

Conclusion

Chikungunya, the disease spreads by Chikungunya virus (CHIKV) is a member of the genus Alphavirus, in the family Togaviridae. Its cause, mode of transmission, detection of virus, symptoms, treatment and prevention is discussed. Vaccine trials have been going on but not yet found any. Mutation of virus causing additional problems for the treatment. NSAIDS are good to reduce fever and pain but aspirin should be avoided in acute stage. Infected patient should be cautious to avoid further mosquito exposure to avoid transmission of disease. All must take protective measures to prevent mosquito breeding and bite by keeping surround clean, periodically emptying the water storages, using proper insecticides and repellents. Each government must take the responsibility to make aware the public about chikungunya fever; so that this ″killing″ sick may keep away from public.

References:

Strauss EG, Strauss JH (1986) Structure and replication of the alphavirus genome. In: Schlesinger S, Schlesinger MJ, editors. The Togaviridae and Flaviviridae. New York: Plenum Press. pp. 35–90.
Porterfield JH (1980) Antigenic characteristics and classification of theTogaviridae. In: Schlesinger R, editor. The Togaviruses. New York: Academic Press. pp. 13–46.
Reinert, J. F., R. E. Harbach & I. J. Kitching (2004). Phylogeny and classification of Aedini (Diptera: Culicidae), based on morphological characters of all life stages. Zool. J. Linn. Soc. 142: 289–368.
Womack, M. (1993). "The yellow fever mosquito, Aedes aegypti.". Wing Beats 5 (4): 4.
Roland Mortimer. Aedes aegypti and Dengue fever. Retrieved on 2007-05-19.
chikungunya virus and evidence for an internal polyadenylation site. J Gen Virol 83: 3075–3084.
http://medicine.plosjournals.org.
Robinson Marion (1955). "An Epidemic of Virus Disease in Southern Province, Tanganyika Territory, in 1952-53; I. Clinical Features". Trans Royal Society Trop Med Hyg 49 (1): 28-32.
Lumsden WHR (1955). "An Epidemic of Virus Disease in Southern Province, Tanganyika Territory, in 1952-53; II. General Description and Epidemiology". Trans Royal Society Trop Med Hyg 49 (1): 33-57.
Ross RW (1956) The Newala epidemic. III. The virus: Isolation, pathogenic properties and relationship to the epidemic. J Hyg 54: 177–191.
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.
http://www.wikipedia.org/wiki/chikungunya
http://www.cycfoundation.org/concepts/Onyong-Nyong-Virus
http://www.cdc.gov/excite/classroom/outbreak/steps.htm
http://www.cdc.gov/ncidod/dvbid/Chikungunya/chikvfact.htm
www.searo.who.int/en/Section10/Section2246.htm
Prescott, L (1993). Microbiology. Wm. C. Brown Publishers. 0-697-01372-3.
Fiers W et al., Complete nucleotide-sequence of bacteriophage MS2-RNA primary and secondary structure of replicase gene, Nature, 260, 500-507, 1976
www.chikungunya.ca
Johnston RE, Peters CJ (1996) Alphaviruses associated primarily with fever and polyarthritis. In: Fields BN, Knipe DM, Howley PM, editors. Fields virology. Philadelphia: Lippincott-Raven Publishers. pp. 843–898.
Jupp PG, McIntosh BM (1988) Chikungunya disease. In: Monath TP, editor. The Arboviruses: Epidemiology and ecology. Boca Raton (Florida): CRC Press. pp. 137–157.
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003 Nov;3(11):722-7.
Charles C. Mann and Mark L. Plummer (1991). The aspirin wars: money, medicine, and 100 years of rampant competition. Boston, Mass: Harvard Business School Press, 25-36. ISBN 0-87584-401-4 Education p. 2–5.
http://www.siddhaphysician.com/Chikungunya-Chicken-Guinea.html
Mosquitoes and Mosquito Repellents -- A Clinician's Guide -- Mark S. Fradin, MD -- Annals of Internal Medicine -- 1 June 1998, Volume 128. Issue 11, 931-940