Zika virus
Pathogen Safety Data Sheets: Infectious Substances – Zika virus
SECTION I – INFECTIOUS AGENT
Name: Zika virus
Agent type: Virus
Family: Flaviviridae
Genus: Flavivirus
Species: Zika virus
Synonym or cross-reference
Abbreviated to ZIKV1. Zika virus is one of several arthropod-borne viruses, which are commonly referred to as “arboviruses”2. Disease associated with Zika virus infection is often termed “Zika fever”3.
Characteristics
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 virus3. Based on non-structural protein 5 gene homology, three main Zika virus lineages have been identified: Asian, East African and West African4 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 proteins1. Virions are spherical, enveloped, and 40-60 nm in diameter6.
Properties
Zika virus is maintained in transmission cycles involving humans, non-human primates, and mosquitoes7.
Section II – Hazard identification
Pathogenicity and toxicity
Approximately 80% of Zika virus infections are asymptomatic or subclinical, suggesting many cases likely go unreported3 8. Symptomatic cases typically manifest as a mild, nonspecific and self-limiting febrile illness lasting up to 7 days; severe disease is uncommon3 8. Common clinical symptoms include maculopapular rash, fever, fatigue, arthralgia, myalgia, headache and conjunctivitis3 8. Less frequent symptoms include sore throat, dry cough, anorexia, nausea, vomiting, loose stool, dizziness, retro-orbital pain, retinal abnormalities and hypertensive iridocyclitis8.
Though rare, neurological complications such as Guillain–Barré syndrome, myelitis and meningoencephalitis may develop approximately 5 to 10 days after acute disease onset9 10. Other complications that may occur include potential impacts on male fertility and cardiovascular diseases such as myocarditis, heart failure and arrhythmia11 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 conditions13.
Vertical (i.e., mother-to-fetus) transmission of Zika virus may occur during all trimesters of pregnancy10. Zika virus infection during pregnancy is associated with an increased risk of preterm birth, fetal death, still birth, and congenital Zika syndrome1. 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 syndrome10. 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 deficits10.
Mammals infected with Zika virus display few, if any, clinical signs14. A sentinel rhesus monkey infected with Zika virus showed only mild pyrexia but this was not conclusively attributed to the virus15. 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 conjunctivitis16 17. Inoculation of pregnant non-human primates with Zika virus results in vertical transmission and signs of congenital Zika syndrome in the fetus18.
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 thereafter15. The first well-documented report of human Zika virus infection occurred in 196419. From 1947 to 2007, only 14 sporadic cases of human infection with Zika virus were reported5 20. The first Zika virus outbreak occurred on Yap Island, Polynesia in 2007, comprising 49 confirmed and 59 probable cases of infection20. Serological testing of the general population of Yap Island estimated that 5005 of the 6892 (73%) residents aged 3 years or older were infected20. 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 population21. Evidence of current or past Zika virus transmission has been reported in Africa, Asia, the Pacific Islands, and the Americas19. Zika virus spread to the Americas in March 2015, where it was first identified in Brazil19. It is estimated that 440,000-1,300,300 cases of Zika virus infection occurred in 2015 in Brazil22.
Zika virus viremia has been reported in non-human primates in Africa and South America14 16 23, and serological studies suggest several animal species in Africa, Asia and the Americas may be susceptible to Zika virus infection14.
Factors influencing the likelihood and severity of symptoms and sequelae associated with Zika virus infection remain unclear1. Zika virus infection during pregnancy is known to cause fetal complications, such as microcephaly, central nervous system abnormalities and fetal death1 10. A patient with immunosuppression showed prolonged persistence of Zika virus RNA in semen, which was detectable for more than 900 days following symptom onset24. In adults, death associated with Zika virus infection is rare and primarily occurs in older patients with pre-existing comorbidities13.
Host range
Natural host(s): Humans and non-human primates are considered to be the primary vertebrate hosts of Zika virus7. 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 occur14 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 pigs14 26 27 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/mL29. In rhesus monkeys, intramuscular injection of 1 x 103 PFU resulted in viremia30 31. Infection of macaques was also achieved through intravaginal or intrarectal inoculation with 7.0 log10 PFU32. In guinea pigs, the median infectious subcutaneous dose was 103.5 PFU33.
Incubation period
3 to 14 days post-exposure2 11.
Communicability
Zika virus transmission primarily occurs through the bite of an infected mosquito vector11. In Africa, Zika virus is maintained in a sylvatic transmission cycle between non-human primates and Aedes mosquitoes7. Human-to-human transmission in urban and peri-urban settings largely occurs through Aedes mosquito vectors8 11.
Vertical transmission in utero from mother to fetus can occur during pregnancy2 11. Sexual transmission is suspected, as evidenced by the report of a traveller who infected his partner after returning from an endemic region2 3 11. Transmission through blood transfusion has been documented11. Transmission through breastfeeding may also occur as the virus has been detected in breast milk, but this has not been confirmed11 34. Zika virus is detected in the saliva of infected individuals; however, the role of saliva in human-to-human transmission remains unclear2 8 11. A case of Zika virus infection was reported in an individual who was bitten by a monkey, although mosquito-borne transmission was also possible35. Laboratory-acquired infection was reported in a graduate student who was bitten by a Zika virus-infected mouse36.
Section III – Dissemination
Reservoir
Humans and non-human primates 37.
Zoonosis
Zika virus is maintained in transmission cycles involving humans, non-human primates, and mosquitoes 7 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 35, and a laboratory-acquired infection was reported in a graduate student who was bitten by a Zika virus-infected mouse 36.
Vectors
Aedes mosquitoes, primarily A. aegypti 7 11 38. Other vectors include A. africanus, A. albopictus, A. hensilii, A. polynesiensis 38. Zika virus has also been isolated from Aedes opok, A. apicoargenteus, A. vittatus, and A. furcifer 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 39 40. Arbidol (also known as umifenovir) showed dose-dependent inhibition of Zika virus in vitro 41. The antimicrobial peptides GF-17 and BMAP-18 showed strong in vitro efficacy against Zika virus 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 43. Dried virus was also inactivated by 5 minutes exposure to the aforementioned disinfectants 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 43. Exposure to temperatures greater than or equal to 60°C for 5 minutes inactivated the virus 43. Zika virus in cell culture medium was inactivated after 5 minutes at 56°C in the absence of serum 44. Zika virus was also inactivated by 10 minute incubation at pH less than or equal to 4 or greater than 11 43.
Survival outside host
Zika virus remains infectious up to 84 hours after drying on a cell culture plate 43 but persists less than 3 days in human breast milk 45.
Section V – First aid/medical
Surveillance
Clinical diagnosis of Zika virus infection is difficult as symptoms often resemble other flavivirus infections 2 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 2 11 46 47. Zika virus RNA is also detectable for more than 10 days in urine 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 2 11. Infection can also be diagnosed through viral culture 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 39 40 46. Treatment is supportive and includes antipyretics, hydration and rest 39 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 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 48 49. Laboratory-acquired infection was reported in a graduate student in Brazil who was bitten by a Zika virus-infected mouse 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 49. Four cases of laboratory-associated Zika virus disease were reported in the United States between 2016-2019 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 36 48 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 11.
Primary hazards
Contact with infectious material 36 49. Needlestick injury and aerosols pose a significant risk of infection 49.
Special hazards
Handling of Zika virus-infected animals poses a risk of infection 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:
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:
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 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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