Chikungunya virus: Infectious substances pathogen safety data sheet

For more information on Chikungunya virus, see the following:

• Chikungunya (Diseases and conditions facts)

Section I – Infectious agent

Name

Chikungunya virus

Agent type

Virus

Taxonomy

Family

Togaviridae

Genus

Alphavirus

Species

chikungunya

Synonym or cross-reference

Chikungunya virus (CHIKV) is an arbovirus that causes chikungunya fever (CHIKF)^{Footnote 1}.

Characteristics

Brief description

CHIKV is a positive-sense, single-stranded RNA virus that measures approximately 11.8 kb^{Footnote 1}. The virion has an icosahedral capsid covered by a lipid layer with a diameter from 60 to 70 nm. The genome possesses a 5' N7-methylguanylated cap and a 3' polyadenylated tail, as well as two coding regions^{Footnote 2}. The first coding region makes up two-thirds of the genome and encodes four non-structural proteins (nsP 1-4) that play a role in genome replication. The second coding region encodes the structural proteins, including the capsid (C), two envelope glycoproteins (E1 and E2), two small cleavage products (E3 and 6K)^{Footnote 1Footnote 2}. Additionally, a transframe (TF) protein is generated from 6K by −1 ribosomal frameshifting^{Footnote 3}.

Properties

The life cycle of alphaviruses begins with receptor-mediated endocytosis^{Footnote 4}. While the receptor for CHIKV has yet to be discovered, heparan sulfate appears to be an important binding partner in cell culture. Old-World alphaviruses rely on clathrin-mediated endocytosis to enter cells where they will escape to the cytoplasm from the early endosomal compartment. There is also evidence that entry can occur directly at the plasma membrane. While still requiring an acidification step, this process is clathrin-independent, which demonstrates how viruses can display wide cell tropisms and how they have the potential to rapidly develop resistance to entry inhibitors. The E1 protein independently mediates fusion of the viral and host cell membranes after undergoing a pH-dependent conformational change. Upon endosomal escape, the nucleocapsid becomes disassembled by ribosomes, and the genome is translated. The non-structural polyprotein is the first to be translated, after which, it undergoes autologous cleavage events resulting in the final mature replicase complex consisting of nsP1/2/3/4. Replication occurs in microinvaginations called spherules that form depending on the activity of nsPs. Their size varies based on the length of the RNA transcribed within. The spherules are proposed to aid in viral immune evasion by sequestering the double-stranded RNA from cytoplasmic pattern recognition receptors and protect RNA from enzymatic digestion. The structural proteins are translated as a polyprotein in the cytosol and the capsid protein will use its serine protease domain to cleave itself from the other proteins. Nucleocapsid assembly occurs in the cytoplasm, and the host secretory system plays a role in transporting the structural proteins to the plasma membrane. Alphaviruses bud directly from the plasma membrane of the infected cell, and it's proposed to be driven by both the preformed nucleocapsid structures and the glycoproteins.

Further, alphaviruses have large 5' and 3' untranslated regions (UTRs) which are biologically active^{Footnote 4}. The 5' UTR promotes translation of viral RNA and helps in evading the interferon response, while the 3' UTR avoids immune bottlenecks existing in the arthropod phase of the life cycle.

Section II – Hazard identification

Pathogenicity and toxicity

The disease is divided into an acute stage, which lasts for one week, and a chronic state, which may persist from months to years^{Footnote 1}. Infection is characterized by an acute fever and polyarthralgia, with arthralgia occurring in 30-90% of cases. Joint pain is often bilateral, symmetric, and debilitating. Occasionally, there may be ophthalmic, neurological, and cardiac symptoms. Cutaneous manifestations, including macular or maculopapular rash on the extremities, trunk, and face, were reported in 40-50% of cases^{Footnote 5}. Skin and mucous membrane lesions have also been identified during the acute stage, including hyperpigmentation, photosensitivity, exfoliative dermatitis, vesicles, bullae, vasculitic lesions, erythema nodosum like lesions, exacerbation of pre-existing dermatoses such as psoriasis, and mucosal ulceration. Gastrointestinal symptoms may occur in 15-47% of cases and are characterized by diarrhea, vomiting, nausea or abdominal pain. Chronic infection may involve symptoms such as rheumatism, fatigue, joint pain, neuritis, rheumatoid arthritis, and ankylosing spondylitis^{Footnote 1}. It is estimated that 30 to 40% of infected individuals experience some long-term sequelae, including persistent arthralgia and/or arthritis^{Footnote 6}.

Epidemiology

CHIKV is maintained in sylvatic transmission cycles, primarily in Africa and Asia, which involve non-human primates and forest-dwelling mosquitoes, and urban transmission cycles involving mosquitoes and humans^{Footnote 5Footnote 6Footnote 7}. It has been detected in sub-Saharan Africa, Indian Ocean Islands, Asia, India, Mediterranean Europe, and the Caribbean. It was first discovered in Tanzania in 1952, causing sporadic outbreaks in sub-Saharan Africa. Epidemics occurred in the Democratic Republic of Congo in 1999-2000, Kenya and Senegal in 2004, Sudan in 2005, Cameroon in 2006, Gabon in 2007 and 2010, and the Republic of Congo in 2011^{Footnote 5}. The strain that emerged from Kenya was responsible for the large-scale outbreak on Reunion Island in the Indian Ocean in 2005-2006^{Footnote 7}. This outbreak led to further spread in Asia and India, as well as Mediterranean Europe, including Italy and France. In 2013, another major outbreak occurred on the Caribbean Saint Martin Island, which contributed to the virus spreading in South America, causing around one million infections. That lineage continues to circulate in Brazil today.

The Reunion Island outbreak of 2005-2006 represents one of the largest outbreaks of disease, with almost one-third of the island's population becoming infected^{Footnote 1}. During the same time period, India reported 1.3 million cases across 13 states^{Footnote 8}. Recent outbreaks have occurred Martinique-Guadeloupe in 2014, affecting 308 000 people and in French Polynesia in 2014-2015, affecting 66 000 people^{Footnote 1}.

Infection with CHIKV is associated with low mortality, but high morbidity^{Footnote 1}. During the Reunion Island outbreak, a case-fatality rate of 1/1000 was reported, but in Brazil, the national case-fatality rate was determined to be 0.13% in 2016, with an incidence rate of 114.70/100,000 and a mortality rate of 0.15/100,000^{Footnote 1Footnote 4Footnote 9}. The average fatality rate is 0.4% and has been found to be higher in children (2.8%) and elderly individuals (1.6%)^{Footnote 10}.

Host range

Natural hosts

Humans, non-human primates, rodents, and birds^{Footnote 1}.

Other hosts

Horses, calves, goats, pigs, dogs, rabbits, armadillos, raccoons, hamsters, mice, reptiles, amphibians, and birds have been experimentally infected^{Footnote 11Footnote 12}.

Infectious dose

The infectious dose is unknown in humans. When cynomolgus macaques were inoculated with 10³ PFU of CHIKV intradermally or intravenously, they developed viremia 1 day post-inoculation (dpi), fever 2 dpi, and morbilliform skin rashes in the first week after inoculation^{Footnote 13}. The dose of 10³ PFU was chosen as it was comparable to the amount of virus secreted from the salivary glands of mosquitoes artificially infected with CHIKV. In Aedes albopictus, a primary CHIKV mosquito vector, the lowest infecting titer was found to be 3.9 log₁₀ pfu/ml, while in Aedes aegypti, it was 5.3 log₁₀ pfu/ml^{Footnote 14}.

Incubation period

The incubation period ranges from 4 to 7 days^{Footnote 1}.

Communicability

The preferred mode of transmission of CHIKV is injection via the mosquito vectors Ae. aegypti and Ae. albopictus^{Footnote 1Footnote 5Footnote 6}. Further, transmission by a contaminated needlestick has been reported in a health care worker^{Footnote 15}. Aerosol transmission has also been proposed in a case of a laboratory-acquired infection^{Footnote 16}. Vertical transmission was observed during the Reunion Island outbreak where infection in infants occurred in 50% of cases where pregnant women had a high viral load during the early phase of labor^{Footnote 17}.

Section III – Dissemination

Reservoir

Vertebrate reservoirs include non-human primates (NHPs), rodents, bats, and possibly birds^{Footnote 5Footnote 18Footnote 19}.

Zoonosis

Indirect zoonosis occurs during both the sylvatic and urban transmission cycles where mosquitoes become infected by vertebrate reservoir hosts and then infect humans^{Footnote 1Footnote 5}.

Vectors

The primary mosquito vectors responsible for the transmission of CHIKV include those belonging to the genus, Aedes^{Footnote 1Footnote 5Footnote 6}. Aedes aegypti and Aedes albopictus have been implicated in the majority of human outbreaks.

Section IV – Stability and viability

Drug susceptibility/resistance

No antivirals are currently available^{Footnote 20}. Repurposed drugs, suramin, favipiravir, sofosbuvir, pimozide, auranofin, pentosan polysulfate (PPS), pixatimob, and ribavirin (alone and synergistically) demonstrated a reduction of pathological signs in vivo.

Susceptibility to disinfectants

CHIKV is inactivated by 20% 1-propanol, 30% 2-propanol, and 40% ethanol^{Footnote 21}. The virus was also fully inactivated by the surface disinfectants Bacillol AF (alcohol-based), Descosept spezial (quaternary ammonium compound based), and Perform (oxygen releasing agent based). Alphaviruses can be inactivated by organic solvents and detergents, 1% sodium hypochlorite, quaternary ammonium compounds, phenolic disinfectants, 70% ethanol, 50% ethanol for 1 hour, 2% glutaraldehyde, and formaldehyde^{Footnote 22}.

Physical inactivation

CHIKV is inactivated by desiccation and temperatures above 58°C^{Footnote 1}. It can also be inactivated by temperatures above 70°C for at least one minute^{Footnote 21}. Alphavirus virions are stable in basic environments with a pH of 7-8 and are inactivated rapidly at acidic pH^{Footnote 22}. Alphaviruses are also susceptible to radiant sunlight, moist or dry heat and drying.

Survival outside host

Alphavirus virions have a half-life of 7 hours at 37°C^{Footnote 22}.

Section V – First aid/medical

Surveillance

CHIKV nucleic acid can be detected in blood, serum, or plasma using reverse-transcription polymerase chain reaction (RT-PCR)^{Footnote 23}. This method is sensitive and specific, and may identify infection during its acute phase (collection within 7 days of symptom onset). Real-time RT-PCR yields quantitative results and viral load assessments. Enzyme-linked immunosorbent assays (ELISAs) are used for the detection of anti-CHIKV antibodies in serum or plasma^{Footnote 1Footnote 23}. IgM levels are highest three to five weeks after infection and persist for up to two months. The plaque reduction neutralization test (PRNT) can also be used to measure neutralizing antibody levels^{Footnote 23}. Viral culture could also provide a definitive diagnosis; however, this is a complex and time-consuming approach.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

Treatments of CHIKF focus on reducing the severity of symptoms through the use of antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs)^{Footnote 1Footnote 23}. Maintenance of proper fluid levels is also important^{Footnote 1}. In cases of severe chronic arthralgia, disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate, hydroxychloroquine, or sulphasalazine, have been proposed^{Footnote 1}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

IXCHIQ (VLA1553) is a live, attenuated vaccine approved for use in Canada as a single dose immunization^{Footnote 24Footnote 25}. The vaccine is safe in non-pregnant individuals 18 years or older.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

There is no known post-exposure prophylaxis^{Footnote 1}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

In 1965, a researcher became infected with CHIKV after attempting to infect mosquitoes with a suspension of 10% infected mouse brain^{Footnote 16}. Following an eight day incubation period, the individual presented with fever, muscular pain, rash, and lymphocytosis. The aerosol route was proposed as the mode of transmission as the researcher did come into direct contact with the viral suspension and was not bitten by a mosquito during the experiment. Prior to 2004, needlestick exposure to CHIKV in the laboratory had resulted in one case of confirmed infection^{Footnote 15}.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

Blood, serum, and plasma^{Footnote 23}.

Primary hazards

Bites of an infected mosquito vector and inhalation of airborne infectious material represent the primary hazards associated with exposure to CHIKV^{Footnote 1Footnote 16}.

Special hazards

Exposure to infected insects while performing CHIKV isolations in endemic areas and working with infected material obtained from those areas in the laboratory^{Footnote 26}.

Section VII – Exposure controls/personal protection

Risk group classification

Alphavirus chikungunya is a Risk Group 3 Human Pathogen, a Risk Group 2 Animal Pathogen, and a Security Sensitive Biological Agent (SSBA)^{Footnote 27Footnote 28}.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. Centrifugation of regulated materials to be carried out in sealed safety cups or rotors that are unloaded in a BSC or other primary containment device using a mechanism that prevents their release. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 29Footnote 30}.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time between the surface and the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and SSBA toxins in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Alphavirus chikungunya require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). A. chikungunya is a terrestrial animal pathogen in Canada; therefore, its importation requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a "Pathogen and Toxin Licence document" for both a Humans Pathogens and Toxins Licence and HAR importation permit.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations

Last file update

January, 2025

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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