Chikungunya-Its Prevention And Cure

Chikungunya is an infection caused by the chikungunya virus. Symptoms include the sudden onset of fever two to four days after exposure. The fever usually lasts two to seven days, while accompanyingjoint pains typically last weeks or months but sometimes years.^[2][3][4] The risk is a little less than 1 in 1,000; the elderly or those with underlying chronic medical problems are most likely to have severe complications.^[5]

The virus is passed to humans by two species of mosquito of the genusAedes: A. albopictus and A. aegypti.^[6][7] The virus circulates within a number of animals including monkeys, birds, cattle, and rodents.^[8] This is in contrast to dengue, for which primates are the only ones affected.^[9]

The best means of prevention is overall mosquito control and the avoidance of bites by mosquitoes in areas where the disease is common.^[10] This may be partly achieved with the use of mosquito nets. No specific treatment is known, but supportive care is recommended, including rest, fluids, and medications to reduce fever and joint pain.^[11]Since 2004, the disease has occurred in outbreaks in Asia, Europe and the Americas.

Signs and symptoms

The incubation period of the chikungunya virus ranges from one to twelve days, and is most typically three to seven.^[12]The disease may be asymptomatic, but generally is not, as 72% to 97% of those infected will develop symptoms.^[12]Characteristic symptoms include sudden onset with high fever, joint pain, and rash. Other symptoms may occur, including headache, fatigue, digestive complaints, and conjunctivitis.^[2]

Information gained during recent epidemics suggests that chikungunya fever may result in a chronic phase as well as the phase of acute illness.^[13] Within the acute phase, two stages have been identified: a viral stage during the first five to seven days, during which viremia occurs,^[14] followed by a convalescent stage lasting approximately ten days, during which symptoms improve and the virus cannot be detected in the blood.^[12] 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.^[14] 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.^[15]

Following the fever, strong joint pain or stiffness occurs; it usually lasts weeks or months, but may last for years. The joint pain can be debilitating, often resulting in near immobility of the affected joints.^[16] Joint pain is reported in 87–98% of cases, and nearly always occurs in more than one joint, though joint swelling is uncommon.^[12] Typically the affected joints are located in both arms and legs, and are affected symmetrically. Joints are more likely to be affected if they have previously been damaged by disorders such as arthritis.^[13] Pain most commonly occurs in peripheral joints, such as the wrists, ankles, and joints of the hands and feet as well as some of the larger joints, typically the shoulders, elbows and knees.^[12][13] Pain may also occur in the muscles or ligaments.

Rash occurs in 40-50% of cases, generally as a maculopapular rash occurring two to five days after onset of symptoms.^[12] Digestive symptoms, including abdominal pain, nausea, vomiting or diarrhea, may also occur.^[2][12][17] In more than half of cases, normal activity is limited by significant fatigue and pain.^[12] Infrequently, inflammation of the eyes may occur in the form of iridocyclitis, or uveitis, and retinal lesions may occur.^[18]

Rarely, neurological disorders have been reported in association with chikungunya virus, including Guillain–Barré syndrome, palsies, meningoencephalitis, flaccid paralysis and neuropathy.^[2] In contrast to dengue fever, Chikungunya fever very rarely causes hemorrhagic complications. Symptoms of bleeding should lead to consideration of alternative diagnoses or co-infection with dengue fever or coexisting congestive hepatopathy.^[14]

.^[32]

Cause

Virology

Chikungunya virus, also referred to as CHIKV, is a member of the alphavirusgenus, and Togaviridae family. It is an RNA virus with a positive-sense single-stranded genome of about 11.6kb.^[34] It is a member of the Semliki Forest virus complex and is closely related to Ross River virus, O’nyong’nyong virus, andSemliki Forest virus.^[35] Because it is transmitted by arthropods, namely mosquitoes, it can also be referred to as an arbovirus (arthropod-borne virus). In the United States, it is classified as a category C priority pathogen,^[36] and work requires biosafety level III precautions.^[37]

Transmission

Chikungunya is generally transmitted from mosquitoes to humans. Less common modes of transmission include vertical transmission, which is transmission from mother to child during pregnancy or at birth. Transmission via infected blood products and through organ donation is also theoretically possible during times of outbreak, though no cases have yet been documented.^[13]

Chikungunya is related to mosquitoes, their environments, and human behavior. The adaptation of mosquitoes to the changing climate of North Africa around 5,000 years ago made them seek out environments where humans stored water. Human habitation and the mosquitoes’ environments were then very closely connected. During periods of epidemics humans are the reservoir of the virus. Because high amounts of virus are present in the blood in the beginning of acute infection, the virus can be spread from a viremic human to a mosquito, and back to a human.^[38]During other times, monkeys, birds and other vertebrates have served as reservoirs.^[39] Three genotypes of this virus have been described, each with a distinct genotype and antigenic character: West African, East/Central/South African, and Asian genotypes.^[40]

Chikungunya is spread through bites from Aedes mosquitoes, and the species A. aegypti was identified as the most common vector, though the virus has recently been associated with many other species, including A. albopictus.^[13]Research by the Pasteur Institute in Paris has suggested chikungunya virus strains in the 2005-2006 Island outbreak incurred a mutation that facilitated transmission by the Asian tiger mosquito (A. albopictus).^[41] Other species potentially able to transmit the chikungunya virus include Ae. furcifer-taylori, Ae. africanus, and Ae. luteocephalus.^[13]

and chronic phase of the disease results in part from interactions between the virus and monocytes and macrophages.^[14] Chikungunya virus disease in humans is associated with elevated serum levels of specific cytokines andchemokines. High levels of specific cytokines have been linked to more severe acute disease: interleukin-6 (IL-6), IL-1β,RANTES, monocyte chemo attractant protein 1 (MCP-1), monokine induced by gamma interferon (MIG), and interferon gamma-induced protein 10 (IP-10). Cytokines may also contribute to chronic chikungunya virus disease, as persistent joint pain has been associated with elevated levels of IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF).^[38] In those with chronic symptoms, a mild elevation of C-reactive protein (CRP) has been observed, suggesting ongoing chronic inflammation. However, there is little evidence linking chronic chikungunya virus disease and the development of autoimmunity.

Viral replication

The virus consists of four nonstructural proteins and three structural proteins.^[14]The structural proteins are the capsid and two envelope glycoprotein’s: E1 and E2, which form heterodimeric spikes on the viron surface. E2 binds to cellular receptors in order to enter the host cell through receptor-mediated endocytosis. E1 contains a fusion peptide which, when exposed to the acidity of the endosome ineukaryotic cells, dissociates from E2 and initiates membrane fusion that allows the release of nucleocapsids into the host cytoplasm, promoting infection.^[53] The mature virion contains 240 heterodimeric spikes of E2/E1, which after release, bud on the surface of the infected cell, where they are released by exocytose to infect other cells.^[34]

Diagnosis

Chikungunya is diagnosed on the basis of clinical, epidemiological, and laboratory criteria. Clinically, acute onset of high fever and severe joint pain would lead to suspicion of chikungunya. Epidemiological criteria consist of whether the individual has traveled to or spent time in an area in which chikungunya is present within the last twelve days (i.e. the potential incubation period). Laboratory criteria include a decreased lymphocyte count consistent with viremia. However a definitive laboratory diagnosis can be accomplished through viral isolation, RT-PCR, or serological diagnosis.^[54]

The differential diagnosis may include infection with other mosquito-borne viruses, such as dengue or malaria, and infection with influenza. Chronic recurrent polyarthralgia occurs in at least 20% of chikungunya patients one year after infection, whereas such symptoms are uncommon in dengue.^[55]

Prevention

Because no approved vaccine exists, the most effective means of prevention are protection against contact with the disease-carrying mosquitoes and controlling mosquito populations by limiting their habitat.^[10] Mosquito control focuses on eliminating the standing water where mosquitoes lay eggs and develop as larva; if elimination of the standing water is not possible, insecticides or biological control agents can be added.^[14] Methods of protection against contact with mosquitoes include using insect repellents with substances such as DEET, icaridin, PMD (p-menthane-3,8-diol, a substance derived from the lemon eucalyptus tree), orIR3535. However, increasing insecticide resistance presents a challenge to chemical control methods.

Wearing bite-proof long sleeves and trousers also offers protection, and 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. As infected mosquitos often feed and rest inside homes, securing screens on windows and doors will help to keep mosquitoes out of the house. In the case of the day-active A. aegypti andA. albopictus, however, this will have only a limited effect, since many contacts between the mosquitoes and humans occur outdoors.

Vaccine

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.^[58] However, 8% of people reported transient joint pain, and attenuation was found to be due to only two mutations in the E2 glycoprotein.^[59]Alternative vaccine strategies have been developed, and show efficacy in mouse models.^[60][61] In August 2014 researchers at the National Institute of Allergy and Infectious Diseases in the USA were testing an experimental vaccine which uses virus-like particles (VLPs) instead of attenuated virus. All the 25 people participated in this phase 1 trial developed strong immune responses.^[62] Phase 2 trial will commence using 400 adults aged 18 to 60 and take place at 6 locations in the Caribbean.^[63] Even with a vaccine, mosquito population control and bite prevention will be necessary to control chikungunya disease.^[64]

Treatment

Currently, no specific treatment for chikungunya is available.^[10] Supportive care is recommended, and symptomatic treatment of fever and joint swelling includes the use of nonsteroidal anti-inflammatory drugs such as naproxen, non-aspirin analgesics such as paracetamol (acetaminophen) and fluids.^[10] Aspirin is not recommended due to the increased risk of bleeding.^[65] Despite anti-inflammatory effects, corticosteroids are not recommended during the acute phase of disease, as they may cause immunosuppression and worsen infection.^[13]

.