INTRODUCTION:

Chikungunya is a infection caused by the chikungunya virus. The virus is unfolded between individuals by 2 forms of mosquitos. Aedes albopictus and Aedes aegypti.(1).They mainly bite during the day.The virus may circulate within a number of animals including birds and rodents.(2) Aedes albopictus (Stegomyia albopicta), from the mosquito (Culicidae) family, also known as (Asian) tiger dipteran or forest dipteran, could be a dipteran native to the tropical and subtropic areas of Southeast Asia; but, within the past few decades, this species has unfold to many countries through the transport of goods and international travel.It is characterized by its black-and-white-striped legs, and small black-and- white-striped body(3). Aedes aegypti, the yellow jack dipteran, could be a dipteran which will unfold dandy fever, chikungunya, Zika fever, Mayaro and yellow jack viruses, and different malady agents.

The dipteran are often recognized by white markings on its legs and a marking within the variety of a harp on the side of its thorax.

This mosquito originated in Africa, [2] but is now found in tropical, subtropical and temperate regions [3] throughout the world (4).

EPIDEMIOLOGY:

CHIKV likely originated in Central/East Africa, where the virus has been found to circulate in a sylvatic cycle between forest-dwelling Aedes species mosquitoes and nonhuman primates. In these areas, sporadic human cases occur, but large human outbreaks are infrequent. However, in urban centres of Africa as well as throughout Asia, the virus can circulate between mosquitoes and naive human hosts in a cycle similar to that of dengue viruses. Aedes aegyptiand Aedes albopictus mosquitoes are the main vectors responsible for urban transmission of CHIKV.(5)

The first significant urban outbreaks of chikungunya fever were documented in the early 1960s in Bangkok and from 1963 through 1973 in India. Minor outbreaks periodically occurred over the next 30 years, but no major outbreaks were recorded until 2004, when a large epidemic started on the coast of Kenya. This outbreak started a 4-year-period in which CHIKV spread throughout numerous islands of the Indian Ocean, India and parts of Southeast Asia chikungunya fever, with a few of these countries developing local autochthonous transmission of the virus.(5)

CHIKV in India served as the source of viral introduction to Italy. A viremic traveller returning to his home after a visit to India was the index case that led to subsequent autocthonous transmission with local Ae. albopictus mosquitoes.(6) A study of the epidemic curve of cases identified in Italy combined with detection of the virus in local Ae. albopictus mosquitoes established that CHIKV was maintained locally in a mosquito-human-mosquito cycle.(7)

SYMPTOMS:

The incubation period of the chikungunya virus ranges from one to twelve days, and is most typically three to seven.The disease may be asymptomatic, but generally is not, as 72% to 97% of those infected will develop symptoms.[8] Characteristic symptoms include sudden onset with high fever, joint pain, and rash. Other symptoms may occur, including headache, fatigue, digestive complaints, and conjunctivitis.[9]

Information gained during recent epidemics suggests that chikungunya fever may result in a chronic phase as well as the phase of acute illness.[10] Within the acute phase, two stages have been identified: a viral stage during the first five to seven days, during which viremia occurs,[11] followed by a convalescent stage lasting approximately ten days, during which symptoms improve and the virus cannot be detected in the blood.[8] Typically, the disease begins with a sudden high fever that lasts from a few days to a week, and sometimes up to ten days. The fever is usually above 39 °C (102°F) and sometimes reaching 40°C (104°F) and may be biphasic—lasting several days, breaking, and then returning. Fever occurs with the onset of viremia, and the level of virus in the blood correlates with the intensity of symptoms in the acute phase.[11] When IgM, an antibody that is a response to the initial exposure to an antigen, appears in the blood, viremia begins to diminish. However, headache, insomnia and an extreme degree of exhaustion remain, usually about five to seven days.[12]

DIAGNOSIS:

Efforts should be directed to carry out the relevant laboratory tests to rule out other mimicsand rule in Chikungunya fever. The gold standard for the diagnosis of Chikungunya fever is viral culture based on inoculation of mosquito cell cultures, mosquitoes, mammalian cell cultures, or mice. However, viral culture is seldom done in routine clinical practice as these facilities are not widely available in India. It has the advantage of detecting a wide range of viruses. RT-PCR, real-time loop-mediated isothermal amplification (RT-LAMP) have also been found to be useful molecular tools for the rapid diagnosis. More frequently, serodiagnostic methods for the detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against Chikungunya virus in acute and convalescent sera are used. These include enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescent method, hemagglutination inhibition, or neutralization techniques. The IgM antibodies are detectable after a mean period of 2 days by ELISA immunofluorescent assay and they persist for periods ranging from several weeks to 3 months. The IgG antibodies can be detected in convalescent samples and persists for years. Instances of persistence of IgM antibodies 18 months after disease onset in about 40% of symptomatic patients has been reported. Thus, these tests appear to be poorly standardized and should be interpreted with caution. (13)

Rapid test IVD

TREATMENT:

Currently there are no vaccines or antivirals for the prevention or treatment of CHIKV infections. Treatment is symptomatic with analgesics, antipyretics and non-steroidal anti-inflammatory agents.

Passive immunization with human IgGs derived from CHIKV infected patients has been shown to be protective in mice against CHIKV challenge. This approach may prove effective for the prevention and treatment of neonates who are at the risk of infection from viraemic mothers. However, this is not cost- effective and it is critical to develop antiviral drugs and/or vaccines for the control of CHIKV infections.(14)

Antiviral compounds:

Chloroquine phosphate was reported to be effective in the treatment of chronic CHIKV arthritis6. However, in a clinical trial of chloroquine in CHIKV infected patients, no difference was observed between the placebo group and the treatment group. Maheshwari et al have also reported that in a mouse model, chloroquine enhances alphavirus replication and aggravates disease pathogenesis. Ribavirin, an antiviral agent was used to treat CHIKV induced arthritis in a small cohort of patients and was found to be beneficial in resolving joint and soft tissue swelling. Briolant et al10have reported a synergistic effect of ribavirin and interferon-α in the inhibition of CHIKV and SFV replication in cell culture. Recently Rulli et al have reported using bindarit, a small molecule anti-inflammatory drug, in a mouse model to effectively treat CHIKV induced arthritis. Bindarit has also been demonstrated to have significant effect in ameliorating RRV induced arthritis (15).

PREVENTION:

SOURCE REDUCTION OF MOSQUITOES:

Since many mosquitoes breed in standing water, source reduction can be as simple as emptying water from containers around the home. This is something that homeowners can accomplish. Mosquito breeding grounds can be eliminated at home by removing unused plastic pools, old tires, or buckets; by clearing clogged gutters and repairing leaks around faucets; by regularly (at most every 4 days) changing water in bird baths; and by filling or draining puddles, swampy areas, and tree stumps. Eliminating such mosquito breeding areas can be an extremely effective and permanent way to reduce mosquito populations without resorting to insecticides. However, this may not be possible in parts of the developing world where water cannot be readily replaced due to irregular water supply.

Open water marsh management (OWMM) involves the use of shallow ditches, to create a network of water flow within marshes and to connect the marsh to a pond or canal. The network of ditches drains the mosquito habitat and lets in fish which will feed on mosquito larvae. This reduces the need for other control methods such as pesticides. Simply giving the predators access to the mosquito larvae can result in long-term mosquito control.(16)

BIOLOGICAL CONTROL:

Biological control or "biocontrol" is the use of natural enemies to manage mosquito populations. There are several types of biological control including the direct introduction of parasites, pathogens and predators to target mosquitoes. Effective biocontrol agents include predatory fish that feed on mosquito larvae such as mosquitofish (Gambusia affinis) and some cyprinids (carps and minnows) and killifish. Tilapia also consume mosquito larvae.(17)

VACCINES:

Like all vaccines under development, CHIKV vaccine candidates developed via various technologies - such as live-attenuated virus vaccines, inactivated viral vaccine, recombinant viral vaccines, chimeric- alphavirus candidates, DNA vaccines and virus-like particles (VLPs)-require an optimal balance between immunogenicity and safety. Of the various vaccine candidates that are in pre-clinical studies, two (MV-CHIK and VRC-CHKVLP059-00-VP) have successfully completed phase I clinical trials 40– 42.

The MV-CHIK vaccine is a recombinant measles virus (MV) that expresses CHIKV surface proteins from the La Reunion ECSA CHIKV strain.Although traditional attenuated live viral vaccines are highly efficient, new approaches using chimeric virus vaccines are proving to be useful. A chimeric viral vaccine combining Eilat virus—an insect-specific alphavirus—and CHIKV structural proteins induced a rapid, long-lasting neutralizing antibody response in C57BL/6 and immunocompromised IFNα/βR −/−mice after a single dose 50. This single-dose efficacy of the vaccine also stimulated similar immunogenicity and protected against CHIKV infection in cynomolgus macaques.(18)

HERBAL TREARTMENT:

There are many side effects by usage of synthetic drugs, to prevent this we can use herbal plants which shows less sides effects. Natural treat is includes,

1. GILOY:

It is believed that Giloy or Guduchi helps in maintaining healthy and sufficient level of white blood cells in our blood. Not only this, this herb also increases the overall effectiveness of these WBCs so as to keep our body protected against any unwanted attacks from foreign bodies. By strengthening our natural defence mechanism, Giloy therefore prepares our body to fight the onset of various types of fever, especially those that directly attack our immune system, such as Chikungunya. This is one dreadful disease which is caused by a mosquito bite and is accompanied by high fever along with severe pain and swelling in the joints. When a person is suffering from the ailment of Chikungunya, the WBC count goes substantially low and that is why the body tends to break down and give in to the disease. It generally takes the affected person a long time to really recover from the symptoms associated with this disease. However, with regular consumption of Tinospora, the White Blood Cells count tends to shoot right up. This subsequently improves our immune system and makes our body fit enough to fight the disease and recover from it as early as possible.(19)

2. IETNAMESE PLANT:

A chemical study of the Vietnamese plant species Trigonostemon howii led to the isolation of a new tigliane-type diterpenoid, trigowiin A, along with several known coumarins and phenylpropanoids. The planar structure and the relative configuration of compound 1 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Trigowiin A exhibited moderate antiviral activity in a virus-cell-based assay for Chikungunya virus (CHIKV). Since the structure of compound 1 is closely related to those of well-known tigliane diterpenoids such as prostratin , phorbol , 12-O-tetradecanoylphorbol 13-acetate (TPA) , and 4α-TPA , the antiviral activity of the latter compounds was also evaluated against CHIKV, as well as in virus-cell- based assays of two additional members of the genus Alphavirus (Sindbis virus, SINV, and Semliki forest virus, SFV). (20)

3. Euphorbia amygdaloides:

Bioassay-guided purification of an EtOAc extract of the whole plant of Euphorbia amygdaloides ssp. semiperfoliata using a chikungunya virus-cell-based assay led to the isolation of six new (1–4, 9, and 10) and six known jatrophane esters. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, and HIV-1 and HIV-2 viruses. Compound 3was found to be the most potent and selective inhibitor of the replication of CHIKV and of HIV-1 and HIV-2 (21)

4. Beriberine:

berberine is a plant-derived isoquinoline alkaloid. They inhibited CHIKV replication in a dose- dependent manner and had broad antiviral activity against other alphaviruses - Semliki Forest virus and Sindbis virus. These compounds caused reduced synthesis of CHIKV genomic and antigenomic viral RNA as well as downregulation of viral protein expression. (22)

5. Trigonostemon cherrieri:

Trigocherrierin A and trigocherriolide E , two new daphnane diterpenoid orthoesters (DDOs), and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV) replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (23).

6. Mammea americana and Tabernaemontana cymose:

Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa. Antiviral effects against viruses such as DENV and CHIKV, demonstrating their ability to inhibit some of the viral replication cycle processes in the cell (from entry to the release of new viruses). The biological activities of these plants, such as antimicrobial, antiparasitic, antitumoral, antifebrile, analgesic, and antiviral properties, have been widely studied, as well as their effects against the larvae and adults of A. aegypti (24)

7. Luteolin and Apigenin:

Luteolin and apigenin rich ethanolic fraction from c. dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.(25)

8. Stillingia lineate:

In an effort to identify new potent and selective inhibitors of chikungunya virus and HIV-1 and HIV-2 virus replication, the endemic Mascarene species Stillingia lineatawas investigated. LC/MS and bioassay-guided purification of the EtOAc leaf extract using a chikungunya virus-cell-based assay led to the isolation of six new and three known tonantzitlolones possessing the rare C20- flexibilane skeleton, along with tonantzitloic acid, a new linear diterpenoid, and three new and two known tigliane-type diterpenoids.(26)

9. Euphorbia pithyusa:

Six new premyrsinol esters and one new myrsinol ester were isolated from an aerial parts extract of Euphorbia pithyusa, together with a known premyrsinol and two known dideoxyphorbol esters, following a bioactivity-guided purification procedure using a chikungunya virus (CHIKV) cell-based assay. The structures of the new diterpene esters were elucidated by MS and NMR spectroscopic data interpretation. Compounds were evaluated against CHIKV replication, and results showed that the 4β-dideoxyphorbol ester was the most active compound (27)

10. Curcumin and Boswellia serrata gum resin:

Traditional medicines are known to have anti-viral effects; therefore, we examined whether curcumin or Boswellia serrata gum resin extract have antiviral activity against CHIKV. Both compounds blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV infection in vitro. In addition, vesicular stomatitis virus vector particles and viral infections were also inhibited to the same extent, indicating a broad antiviral activity. Although the bioavailability of these compounds is rather poor, they

might be used as a lead structure to develop more effective antiviral drugs or might be used topically to prevent CHIKV spread in the skin after mosquito bites.(28)

11. Vitamin C:

Vitamin C supplemented orally has its limitations in achieving high blood (i.e., plasma) levels, whereas the use of intravenous vitamin C (IVC) can reach blood levels that possess distinct clinical and pharmacological advantages. Vitamin C is absorbed in the gastrointestinal tract, where the body metabolizes a limited amount and the rest is excreted through the kidneys.8 However, if the vitamin is administered intravenously it can reach plasma concentrations that are 30 to 70 times higher than the oral pathway.

Ascorbic acid is also a nutrient for the immune system. Treatment of ascorbic acid in vitro resulted in an increase in T-cells and natural killer (NK)-cells, which constitute one of the main components of the adaptive immune system which fights against viruses and intracellular bacteria.3 It has been suggested the same effect can be achieved by IVC administration.

In case of Chikungunya fever, treated with high doses (100g/day) of IVC in a period of two days and without any side effects.(29)

REFERECES:

1. "chikungunya". Oxford Learner's Dictionary. Oxford University Press. Archived from the original on 4 November 2014. Retrieved 4 November 2014.

2. "Chikungunya Virus Symptoms, Diagnosis, and Treatment". CDC. 6 April 2016. Archived from the original on 21 September 2016. Retrieved 26 September 2016.

3. Scholte, J.-E.; Schaffner, F. (2007). "Waiting for the tiger: establishment and spread of the Aedes albopictus mosquito in Europe". In Takken, W.; Knols, B. G. J. Emerging pests and vector-borne diseases in Europe. 1. Wageningen Academic Publishers. ISBN 978-90-8686-053-1.

4. Laurence Mousson; Catherine Dauga; Thomas Garrigues; Francis Schaffner; Marie Vazeille; Anna- Bella Failloux (August 2005). "Phylogeography of Aedes (Stegomyia) aegypti (L.) and Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae) based on mitochondrial DNA variations". Genetics Research. 86 (1): 1–11. doi:10.1017/S0016672305007627. PMID 16181519.

5. Powers AM, Logue CH. Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus, J Gen Virol, 2007, vol. 88 (pg. 2363-77)

6. Angelini R, Finarelli AC, Angelini P, et al. An outbreak of chikungunya fever in the province of Ravenna, Italy, Euro Surveill, 2007, vol. 12 pg. E0709061

7. Angelini R, Finarelli AC, Angelini P, et al. An outbreak of chikungunya fever in the province of Ravenna, Italy, Euro Surveill, 2007, vol. 12 pg. E0709061

8. Thiberville, Simon-Djamel; Moyen, Nanikaly; Dupuis-Maguiraga, Laurence; Nougairede, Antoine; Gould, Ernest A.; Roques, Pierre; de Lamballerie, Xavier (2013). "Chikungunya fever: Epidemiology, clinical syndrome, pathogenesis and therapy". Antiviral Research. 99 (3): 345–370. doi:10.1016/j.antiviral.2013.06.009. ISSN 0166-3542.

9. 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.

10. Burt, Felicity J; Rolph, Micheal S; Rulli, Nestor E; Mahalingam, Suresh; Heise, Mark T (2012). "Chikungunya: a re-emerging virus". The Lancet. 379 (9816): 662–671. doi:10.1016/S0140- 6736(11)60281-X. ISSN 0140-6736. PMID 22100854

11. Weaver, Scott C.; Lecuit, Marc (2015). "Chikungunya Virus and the Global Spread of a Mosquito- Borne Disease". New England Journal of Medicine. 372 (13): 1231–1239. doi:10.1056/NEJMra1406035. ISSN 0028-4793. PMID 25806915

12. Chhabra M, Mittal V, Bhattacharya D, Rana U, Lal S (2008). "Chikungunya fever: a re-emerging viral infection". Indian J Med Microbiol (Submitted manuscript). 26 (1): 5–12. doi:10.4103/0255- 0857.38850. PMID 18227590.

13. Indian J Dermatol. 2010 Jan-Mar; 55(1): 54–63.doi: [10.4103/0019-5154.60355]PMCID: PMC2856377PMID: 20418981Alladi Mohan, DHN Kiran, I Chiranjeevi Manohar, and D Prabath Kumar

14. Couderc T, Khandoudi N, Grandadam M, Visse C, Gangneux N, Bagot S, et al. Prophylaxis and therapy for Chikungunya virus infection. J Infect Dis. 2009; 200:516–23. [PubMed]

15. Approaches to the treatment of disease induced by chikungunya virus Jayaram Bettadapura, Lara J. Herrero, [...], and SSuresh

16. Florida Mosquito Control (White Paper). Florida Coordinating Council on Mosquito Control. Archived from the original on 28 October 2008.

14. Jianguo, Wang; Dashu, Ni (1995). "31. A Comparative Study of the Ability of Fish to Catch Mosquito Larva". In MacKay, Kenneth T. Rice-fish culture in China. International Development Research Centre. ISBN 1-55250-313-5. Archived from the original on 9 June 2011.

15. Chikungunya: vaccines and therapeutics Kothila Tharmarajah, Writing – Original Draft Preparation, Writing – Review and Editing, Suresh Mahalingam,

16. Effectiveness of Guduchi / Giloy (Tinospora cordifolia) Extracts in Chikungunya fever by Dr. sonica krishnan

17. Prostratin and 12-O-Tetradecanoylphorbol 13-Acetate Are Potent and Selective Inhibitors of Chikungunya Virus Replication

18. Mélanie Bourjot, Leen Delang, Van Hung Nguyen, Johan Neyts, Françoise Guéritte, Pieter Leyssen and Marc Litaudon

19. Jatrophane Diterpenes as Inhibitors of Chikungunya Virus Replication: Structure–Activity Relationship and Discovery of a Potent Lead Louis-Félix Nothias-Scaglia, Pascal Retailleau, Julien Paolini, Christophe Pannecouque, Johan Neyts, Vincent Dumontet, Fanny Roussi, Pieter Leyssen, Jean Costa and Marc Litaudon

20. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses Finny S. Varghesea1TeroAhola

21. Trigocherrierin A, a Potent Inhibitor of Chikungunya Virus Replication Mélanie Bourjot 1, Pieter Leyssen 2, Johan Neyts 2, Vincent Dumontet 3 and Marc Litaudon 3,*

22. Antiviral effect of compounds derived from the seeds of Mammea americanaand Tabernaemontana cymosa on Dengue and Chikungunya virus infections

23. Cecilia Gómez-Calderón, Carol Mesa-Castro, Sara Robledo, Sergio Gómez, Santiago Bolivar- Avila, Fredyc Diaz-Castillo andMarlen Martínez-Gutierrez

24. Anti—chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon

25. Krishnan Saravana Murali, Srinivasan Sivasubramanian, Savariar Vincent, Shanmugaraj Bala Murugan, Bupesh Giridaran, Sundaram Dinesh, Palani Gunasekaran, Kaveri Krishnasamy, Ramalingam Sathishkumar

26. Antiviral Activity of Flexibilane and Tigliane Diterpenoids from Stillingia lineata Florent Olivon†, Héliciane Palenzuela†, Emmanuelle Girard-Valenciennes‡, Johan Neyts§, Christophe Pannecouque§, Fanny Roussi†, Isabelle Grondin‡, Pieter Leyssen§ and Marc Litaudon*†

27. Isolation of Premyrsinane, Myrsinane, and Tigliane Diterpenoids from Euphorbia pithyusa Using a Chikungunya Virus Cell-Based Assay and Analogue Annotation by Molecular Networking

28. Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro Author links open overlay panel

29. High Dose Intraveneous Vitamin C and Chikungunya Fever: A Case Report Michael J. Gonzalez, NMD, DSc, PhD, FANMA, FACN, Jorge R. Miranda-Massari, PharmD, [...], and Vicente J. Cobas- Rosario, BS

Received on 08.12.2018 Modified on 20.01.2019

Res. J. Pharma. Dosage Forms and Tech.2019; 11(2): 137-142.

DOI: 10.5958/0975-4377.2019.00023.5