Zika virus: Infectious substances pathogen safety data sheet

For more information on Zika virus, see the following:

• Biosafety advisory on Zika virus
• Travel health notice on Zika virus: Advice for travellers
• Zika virus

Section I – Infectious agent

Name

Zika virus

Agent type

Virus

Taxonomy

Family

Flaviviridae

Genus

Flavivirus

Species

Zika virus

Synonym or cross-reference

Abbreviated to ZIKV^{Footnote 1}. Zika virus is one of several arthropod-borne viruses, which are commonly referred to as "arboviruses"^{Footnote 2}. Disease associated with Zika virus infection is often termed "Zika fever"^{Footnote 3}.

Characteristics

Brief description

Zika virus is a positive-sense, single-stranded RNA arbovirus belonging to the genus Flavivirus and family Flaviviridae, which include other notable human pathogens such as West Nile virus, Dengue virus, Tick-borne encephalitis virus and Yellow fever virus^{Footnote 3}. Based on non-structural protein 5 gene homology, three main Zika virus lineages have been identified: Asian, East African and West African^{Footnote 4Footnote 5}. The genome is approximately 11 kilobases in length and encodes one large polyprotein that is processed by viral and host proteases into three structural and seven non-structural proteins^{Footnote 1}. Virions are spherical, enveloped, and 40-60 nm in diameter^{Footnote 6}.

Properties

Zika virus is maintained in transmission cycles involving humans, non-human primates, and mosquitoes^{Footnote 7}.

Section II – Hazard identification

Pathogenicity and toxicity

Approximately 80% of Zika virus infections are asymptomatic or subclinical, suggesting many cases likely go unreported^{Footnote 3Footnote 8}. Symptomatic cases typically manifest as a mild, nonspecific and self-limiting febrile illness lasting up to 7 days; severe disease is uncommon^{Footnote 3Footnote 8}. Common clinical symptoms include maculopapular rash, fever, fatigue, arthralgia, myalgia, headache and conjunctivitis^{Footnote 3Footnote 8}. Less frequent symptoms include sore throat, dry cough, anorexia, nausea, vomiting, loose stool, dizziness, retro-orbital pain, retinal abnormalities and hypertensive iridocyclitis^{Footnote 8}.

Though rare, neurological complications such as Guillain–Barré syndrome, myelitis and meningoencephalitis may develop approximately 5 to 10 days after acute disease onset^{Footnote 9Footnote 10}. Other complications that may occur include potential impacts on male fertility and cardiovascular diseases such as myocarditis, heart failure and arrhythmia^{Footnote 11Footnote 12}. In adults, Zika virus infection is associated with an extremely low case fatality rate, with the majority of deaths occurring in older patients with pre-existing conditions^{Footnote 13}.

Vertical (i.e., mother-to-fetus) transmission of Zika virus may occur during all trimesters of pregnancy^{Footnote 10}. Zika virus infection during pregnancy is associated with an increased risk of preterm birth, fetal death, still birth, and congenital Zika syndrome^{Footnote 1}. Congenital Zika syndrome is characterized by microcephaly, abnormal brain development, limb contractures, eye abnormalities, brain calcifications and other neurological complications. Estimates of neonatal mortality in the first week of life range from 4 to 7% among infants with congenital Zika syndrome^{Footnote 10}. Despite lacking clinical or radiological signs of congenital Zika syndrome, children born to Zika virus-infected mothers may later experience seizures, hearing loss, visual impairment, dysphagia and developmental deficits^{Footnote 10}.

Mammals infected with Zika virus display few, if any, clinical signs^{Footnote 14}. A sentinel rhesus monkey infected with Zika virus showed only mild pyrexia but this was not conclusively attributed to the virus^{Footnote 15}. There are no reports of disease clearly associated with Zika virus in other natural animal hosts in which neutralizing antibodies against the virus have been detected. Experimentally inoculated monkeys develop viremia and show signs of lethargy, decreased motility, rash, fever, lymphadenopathy and conjunctivitis^{Footnote 16Footnote 17}. Inoculation of pregnant non-human primates with Zika virus results in vertical transmission and signs of congenital Zika syndrome in the fetus^{Footnote 18}.

Epidemiology

Zika virus was first isolated in 1947 from a sentinel rhesus monkey in the Zika forest of Uganda, and was also isolated from mosquitoes collected in this region shortly thereafter^{Footnote 15}. The first well-documented report of human Zika virus infection occurred in 1964^{Footnote 19}. From 1947 to 2007, only 14 sporadic cases of human infection with Zika virus were reported^{Footnote 5Footnote 20}. The first Zika virus outbreak occurred on Yap Island, Polynesia in 2007, comprising 49 confirmed and 59 probable cases of infection^{Footnote 20}. Serological testing of the general population of Yap Island estimated that 5005 of the 6892 (73%) residents aged 3 years or older were infected^{Footnote 20}. A second outbreak involving 30,000-32,000 symptomatic cases (11.5% of the population) occurred in French Polynesia in 2013-2014, and seroprevalence following the outbreak was 49% in the general population^{Footnote 21}. Evidence of current or past Zika virus transmission has been reported in Africa, Asia, the Pacific Islands, and the Americas^{Footnote 19}. Zika virus spread to the Americas in March 2015, where it was first identified in Brazil^{Footnote 19}. It is estimated that 440,000-1,300,300 cases of Zika virus infection occurred in 2015 in Brazil^{Footnote 22}.

Zika virus viremia has been reported in non-human primates in Africa and South America^{Footnote 14Footnote 16Footnote 23}, and serological studies suggest several animal species in Africa, Asia and the Americas may be susceptible to Zika virus infection^{Footnote 14}.

Factors influencing the likelihood and severity of symptoms and sequelae associated with Zika virus infection remain unclear^{Footnote 1}. Zika virus infection during pregnancy is known to cause fetal complications, such as microcephaly, central nervous system abnormalities and fetal death^{Footnote 1Footnote 10}. A patient with immunosuppression showed prolonged persistence of Zika virus RNA in semen, which was detectable for more than 900 days following symptom onset^{Footnote 24}. In adults, death associated with Zika virus infection is rare and primarily occurs in older patients with pre-existing comorbidities^{Footnote 13}.

Host range

Natural host(s)

Humans and non-human primates are considered to be the primary vertebrate hosts of Zika virus^{Footnote 7}. Serological evidence of infection has been reported for sheep, goats, horses, cattle, carabao, ducks, bats, pigs, buffalo, elephants, rodents, hippos, impala, kongoni, lions, wildebeest and zebras; however, serological studies should be interpreted with caution as cross-reactivity with other flaviviruses may occur^{Footnote 14Footnote 25}.

Other host(s)

Following experimental inoculation with Zika virus, viremia was detected in frogs, armadillos, neonatal pigs, mice, bats and non-human primates, and seroconversion was observed in goats, rabbits, ducks, frogs, and pigs^{Footnote 14Footnote 26Footnote 27Footnote 28}.

Infectious dose

The infectious dose for Zika virus in humans is unknown. In Aedes aegypti mosquitoes, the 50% infectious dose (ID⁵⁰) was 6.1-7.5 log₁₀ plaque-forming units (PFU)/mL, with a minimum infectious dose of 4.2 log₁₀ PFU/mL^{Footnote 29}. In rhesus monkeys, intramuscular injection of 1 x 10³ PFU resulted in viremia^{Footnote 30Footnote 31}. Infection of macaques was also achieved through intravaginal or intrarectal inoculation with 7.0 log₁₀ PFU^{Footnote 32}. In guinea pigs, the median infectious subcutaneous dose was 10^3.5 PFU^{Footnote 33}.

Incubation period

3 to 14 days post-exposure^{Footnote 2Footnote 11}.

Communicability

Zika virus transmission primarily occurs through the bite of an infected mosquito vector^{Footnote 11}. In Africa, Zika virus is maintained in a sylvatic transmission cycle between non-human primates and Aedes mosquitoes^{Footnote 7}. Human-to-human transmission in urban and peri-urban settings largely occurs through Aedes mosquito vectors^{Footnote 8Footnote 11}.

Vertical transmission in utero from mother to fetus can occur during pregnancy^{Footnote 2Footnote 11}. Sexual transmission is suspected, as evidenced by the report of a traveller who infected his partner after returning from an endemic region^{Footnote 2Footnote 3Footnote 11}. Transmission through blood transfusion has been documented^{Footnote 11}. Transmission through breastfeeding may also occur as the virus has been detected in breast milk, but this has not been confirmed^{Footnote 11Footnote 34}. Zika virus is detected in the saliva of infected individuals; however, the role of saliva in human-to-human transmission remains unclear^{Footnote 2Footnote 8Footnote 11}. A case of Zika virus infection was reported in an individual who was bitten by a monkey, although mosquito-borne transmission was also possible^{Footnote 35}. Laboratory-acquired infection was reported in a graduate student who was bitten by a Zika virus-infected mouse^{Footnote 36}.

Section III – Dissemination

Reservoir

Humans and non-human primates^{Footnote 37}.

Zoonosis

Zika virus is maintained in transmission cycles involving humans, non-human primates, and mosquitoes^{Footnote 7Footnote 37}. A case of Zika virus infection was reported in an individual who was bitten by a monkey, although mosquito-borne transmission was also possible^{Footnote 35}, and a laboratory-acquired infection was reported in a graduate student who was bitten by a Zika virus-infected mouse^{Footnote 36}.

Vectors

Aedes mosquitoes, primarily A. aegypti^{Footnote 7Footnote 11Footnote 38}. Other vectors include A. africanus, A. albopictus, A. hensilii, A. polynesiensis^{Footnote 38}. Zika virus has also been isolated from Aedes opok, A. apicoargenteus, A. vittatus, and A. furcifer^{Footnote 38}.

Section IV – Stability and viability

Drug susceptibility/resistance

Currently, there are no approved drugs to treat Zika virus infection, although antivirals such as nucleoside analogs are being evaluated for potential anti-Zika virus activity^{Footnote 39Footnote 40}. Arbidol (also known as umifenovir) showed dose-dependent inhibition of Zika virus in vitro^{Footnote 41}. The antimicrobial peptides GF-17 and BMAP-18 showed strong in vitro efficacy against Zika virus^{Footnote 42}.

Susceptibility to disinfectants

Zika virus stocks are inactivated by 70% isopropanol, 70% ethanol, 70% incidin, 70% DMSO/E, 1% hypochlorite, 2% paraformaldehyde, or 2% gluteraldehyde following a 1-minute incubation period^{Footnote 43}. Dried virus was also inactivated by 5 minutes exposure to the aforementioned disinfectants^{Footnote 43}.

Physical inactivation

Complete inactivation of Zika virus in 2.5% fetal calf serum (FCS) occurred following 10 minute exposure to UV radiation; however, longer exposure is required in the presence of higher concentrations of FCS^{Footnote 43}. Exposure to temperatures greater than or equal to 60°C for 5 minutes inactivated the virus^{Footnote 43}. Zika virus in cell culture medium was inactivated after 5 minutes at 56°C in the absence of serum^{Footnote 44}. Zika virus was also inactivated by 10 minute incubation at pH less than or equal to 4 or greater than 11^{Footnote 43}.

Survival outside host

Zika virus remains infectious up to 84 hours after drying on a cell culture plate^{Footnote 43} but persists less than 3 days in human breast milk^{Footnote 45}.

Section V – First aid/medical

Surveillance

Clinical diagnosis of Zika virus infection is difficult as symptoms often resemble other flavivirus infections^{Footnote 2Footnote 46}. During the symptomatic phase (i.e., within 7 days of symptom onset), molecular testing using reverse transcription polymerase chain reaction (RT-PCR) on whole blood or serum is the diagnostic method of choice^{Footnote 2Footnote 11Footnote 46Footnote 47}. Zika virus RNA is also detectable for more than 10 days in urine^{Footnote 11}. Serological methods such as enzyme immunoassays, immunofluorescence assays, and neutralization assays are typically used at 7 or more days post-symptom onset; although these methods are limited by potential cross-reactivity with other flaviviruses^{Footnote 2Footnote 11}. Infection can also be diagnosed through viral culture^{Footnote 47}.

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 (CBH).

First aid/treatment

To date, there are no specific therapeutics for the treatment of Zika virus infection^{Footnote 39Footnote 40Footnote 46}. Treatment is supportive and includes antipyretics, hydration and rest^{Footnote 39Footnote 46}.

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 CBH.

Immunization

There is no approved vaccine currently available; however, dozens of candidate vaccines are currently under development, some of which have entered clinical trials^{Footnote 39}.

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

Prophylaxis

None.

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

Section VI – Laboratory hazard

Laboratory-acquired infections

A case of a laboratory-acquired Zika virus infection was reported in 1973 and involved an individual working in an arboviral laboratory in Uganda; the route of exposure was unknown^{Footnote 48Footnote 49}. Laboratory-acquired infection was reported in a graduate student in Brazil who was bitten by a Zika virus-infected mouse^{Footnote 36}. Global laboratory surveys conducted in 1976 and 1978 documented three cases of laboratory-acquired Zika virus disease; the suspected sources of exposure were aerosols or unknown^{Footnote 49}. Four cases of laboratory-associated Zika virus disease were reported in the United States between 2016-2019^{Footnote 49}. Two of these cases were associated with needlestick injury, and the route of exposure was unknown for the other two cases. Death or serious sequelae resulting from laboratory-acquired Zika virus infection has not been reported to date^{Footnote 36Footnote 48Footnote 49}.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Zika virus can be detected in amniotic fluid, brain tissue, placenta, vaginal secretions, tears, breast milk, semen, testes, blood and serum, saliva, urine^{Footnote 11}.

Primary hazards

Contact with infectious material^{Footnote 36Footnote 49}. Needlestick injury and aerosols pose a significant risk of infection^{Footnote 49}.

Special hazards

Handling of Zika virus-infected animals poses a risk of infection^{Footnote 36}.

Section VII – Exposure controls/personal protection

Risk group classification

Zika virus is a Risk Group 2 human pathogen and a Risk Group 2 animal pathogen, and is listed on Schedule 2 of the Human Pathogens and Toxins Act.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS and in the Biosafety advisory for Zika virus for work involving infectious or potentially infectious materials, animals, or cultures.

Learn more about:

• Biosafety advisory for Zika virus

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the CBS to be followed. At minimum, it is recommended to use a labcoat and closed-toes cleanable shoes, gloves when direct skin contact with infected materials or animals is unavoidable.

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 and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain Zika virus, the following resources may be consulted:

• Human Diagnostic Activities biosafety guideline
• Local risk assessment biosafety guidelines

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 before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials should be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Zika virus require a Human Pathogens and Toxins licence issued by the Public Health Agency of Canada^{Footnote 50}. Zika virus is a non-indigenous animal pathogen in Canada; therefore, importation of Zika virus requires an import permit, issued by the Canadian Food Inspection Agency. The following is a non-exhaustive list of applicable designations, regulations, or legislations:

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

Last file update

September, 2021

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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