Rapid Risk Assessment: The risk of Zika virus to Canadians (first update)

The risk assessment is reviewed on a regular basis, and is updated as required.

Last reviewed: 28 April 2016
Last updated: 28 April 2016

What’s New?

  • There is now scientific consensus that ZIKV causes: infant microcephaly and other severe brain anomalies; and, post-infection sequelae like GBS. We have updated our assessment accordingly, including removing much of the descriptive review related to these conditions as the relationship is now considered causal.
  • Sexual transmission continues to be reported, including a documented case of transmission from a male traveller to his male partner.

Summary

  • An epidemic of mosquito-borne Zika virus (ZIKV) is occurring in many parts of the Americas and several other tropical/sub-tropical areas. The virus causes no or relatively mild illness in most adults. However, it is now known that Zika virus is a cause of more severe outcomes like congenital abnormalities in the fetus and  Guillain Barré Syndrome (GBS) in infected people.
  • The mosquito implicated as the primary vector (Aedes aegypti) of ZIKV does not occur in Canada. Other implicated vectors (e.g., Aedes albopictus) are not known to be established in Canada. There also are substantial barriers to long-term maintenance of ZIKV in Canada. Hence, risk of establishment of ZIKV in Canada is considered negligible. Local epidemic or endemic transmission is assessed as very unlikely (Very Low likelihood, with high confidence).
  • Travel-related ZIKV infections have been reported among Canadian travellers. For the individual, it is estimated that travel to an affected area is associated with a medium chance of infection with ZIKV (Medium likelihood, with high confidence).
  • Sexual transmission, from symptomatic male travellers to a sexual partner (female or male) who has not travelled, has been reported. Because the likelihood of infection with ZIKV is considered low, so too is the likelihood of transmission via this route (Low likelihood, medium confidence). However, if a man does become infected with ZIKV, the likelihood of transmission to his sexual partner is assessed as Medium (low confidence).
  • For most infected travellers, ZIKV will have little or no health impact (Low impact, with medium confidence). However, severe outcomes (e.g., GBS) might occur in some affected individuals (High impact, high confidence).
  • Based on recent evidence, we assess that there could be Very High impact (with high confidence) to the unborn children of women who become infected with ZIKV while pregnant.
  • Canadian recommendations for the prevention and management of ZIKV-disease have been developed by the Committee to Advise on Tropical Medicine and Travel.

  1. Date of initial assessment
    28 January 2016
  2. Date of last update
    20 April 2016
  3. Risk identification
    Individual and public health risk to Canadians associated with the 2015/16 ZIKV outbreak in the Americas.
  4. Prepared by
    Public Health Agency of Canada, with expert consultation from the Department of National Defence, Force Health Protection
  5. Key information sources
    See Reference list
  6. Review & update
    This assessment will be revised as required, informed by a continuous review of outbreak data and the scientific literature. Triggers for a revision include substantial change in epidemiology, new scientific developments, or increased rates of severe outcomes.

Document information

In this Rapid Risk Assessment (RRA) document we assess the risk to Canadians posed by the ongoing Zika virus (ZIKV) epidemic. We separately consider the likelihood of infection with ZIKV and the impact of infection. We consider the likelihood of infection for (i) Canadians remaining in Canada (by assessing the likelihood of local mosquito-associated or sexual transmission), and (ii) Canadians travelling to countries with ongoing ZIKV activity. We then consider the impact of ZIKV infection. The terms “likelihood”, “impact”, and “confidence” are used in a specific sense, and are defined in Appendix 1.

Our assessments will change as more information becomes available, and this document will be updated accordingly.

Disease background information

Infectious agent

Zika virus disease is a mosquito-associated flaviviral disease caused by Zika virus (ZIKV). It is related to other Flaviviridae, including Japanese Encephalitis, West Nile, Yellow Fever, St. Louis Encephalitis, and Dengue viruses.

Transmission modes

The natural cycle of ZIKV involves mosquito vectors and vertebrate hosts, probably African primatesReference 1 Reference 2 Reference 3. There is limited documentation of non-primate reservoirs of ZIKV; serological evidence has been demonstrated in rodentsReference 4, but their role (if any) in transmission is unknown. Once infected, a mosquito is thought to remain so for their lifetimeReference 5. Aside from mosquitos, blood transfusion-associatedReference 6 Reference 7 Reference 8 and sexual transmission (via semen) have been documented. The latter includes several instances where symptomatic male travellers infected their partner (female or male), who had not travelledReference 9 Reference 10 Reference 11 Reference 12.

A significant concern with the current ZIKV outbreak is the potential for vertical transmission from mother to infantReference 13 Reference 14 Reference 15 Reference 16 which is a cause of microcephaly and other congenital abnormalitiesReference 14 Reference 15 Reference 16 Reference 17 Reference 18 Reference 19 Reference 20 Reference 21.

Vector

Aedes aegypti is considered the primary vector of ZIKV (as well as Dengue and Yellow fever virus). This mosquito is largely restricted to tropical and subtropical regions, though more northern populations may occur in isolated refugesReference 22. Ae. albopictus also has been implicated as a vector, though its role in the current outbreak is uncertain. This species is widely distributed outside the tropicsReference 23, but is not known to be established in Canada.

Epidemiology

Human infections with ZIKV were first identified in Uganda and Tanzania in 1952 Reference 3 Reference 24. Over the next 50 years, few cases were reported and human ZIKV infection was restricted to Africa and parts of Asia. In 2007, the first major outbreak outside of these areas was reported on the island of Yap (Micronesia) in the southwestern Pacific Ocean Reference 25. Between 2013 and 2015, additional outbreaks occurred on islands and archipelagos in the Pacific region including a large outbreak in French Polynesia Reference 26 Reference 27. An outbreak was also reported in Cape Verde Reference 28. More recently, the virus has caused widespread outbreaks across Central and South America, Mexico, and the Caribbean, with some activity also occurring in Asia and the South Pacific.

Clinical presentation

Asymptomatic infections appear to be the norm; only one in four or five people (20-25%) infected with ZIKV are believed to develop clinical symptoms Reference 25 Reference 29. Disease is generally relatively mild, with symptoms that include: low-grade fever (usually <38.5°C), transient arthritis/arthralgia with possible joint swelling mainly in the smaller joints of the hands and feet, maculo-papular rash often spreading from the face to the body, conjunctival hyperaemia or bilateral non-purulent conjunctivitis, and general non-specific symptoms such as myalgia, asthenia, and headaches Reference 25. Less commonly, infection with ZIKV is now known as a cause of serious complications such as Guillain Barré Syndrome (GBS)Reference a Reference 18 Reference 30 Reference 31 and other neurologic complicationsReference 32 Reference 33. There have been a handful of reports of ZIKV-associated deaths in adultsReference 15.

The incubation period (i.e. the amount of time between exposure and symptom onset) is thought to range from 3 to 12 days Reference 34. The disease symptoms are usually mild and last for 2 to 7 days. Most people recover fully without severe complications, and hospitalization rates are low Reference 25. Viremia (the period when ZIKV is measurably present in the blood) has been estimated as lasting 3 to 5 days following symptom onset Reference 35 Reference 36, although viral RNA has been detected in saliva Reference 37 or urine Reference 38 more than a week after clearance from the blood. Infection may go unrecognized or be misdiagnosed as dengue, chikungunya, or other viral infections causing fever and rash.

Event background information

Between 2013 and 2015, several significant outbreaks were noted on islands and archipelagos from the Pacific region including a large outbreak in French PolynesiaReference 26 Reference 27. In 2015, ZIKV emerged in South America with widespread outbreaks reported in Brazil and Colombia. Locally acquired cases have been reported to WHO by many countries, mostly in the Americas (see the Agency’s list of affected countries). Evidence is accumulating that infection with ZIKV is associated with congenital abnormalities among children born to mothers infected during pregnancy, as well as with neurologic complications in a small proportion of infected persons. Information related to the ZIKV outbreak is rapidly evolving. For a summary of the most up-to-date information related to the ZIKV outbreak, readers are referred to the World Health Organization situation report.

Risk assessment

In this section, we consider i) the likelihood of infection with ZIKV for Canadians who have not travelled to an area where ZIKV is actively circulating, ii) the potential for local transmission (i.e., in Canada) of ZIKV, and iii) the likelihood of infection with ZIKV for travelling Canadians. We then separately consider the impact for individuals who become infected, first in the general case and then specifically for the unborn child of a woman infected while pregnant.

Likelihood of infection with ZIKV via blood and sexual transmission for Canadians who have not travelled

Human-to-human transmission of ZIKV can occur through several routes, including sexuallyReference 11 and via contaminated bloodReference 7. Individual Canadians who do not travel to areas of ongoing ZIKV outbreaks could be exposed to ZIKV in Canada via these routes.

Because ZIKV does not persist for long in the blood (typically 3-5 days following symptom onset)Reference 35 Reference 36, there is a narrow window for blood-based transmission. In general, almost all individuals should clear infection from their blood within 21 days (combining 12 days for incubation and an additional 9 days for blood viremia; personal communication, Dr. Scott Weaver, 24 January 2016). Given that Canadian blood safety agencies have enacted a 21-day donor deferral period following travel to ZIKV outbreak countries, the likelihood of transmission via this route is assessed as Very Low (with high confidence).

Several cases of sexual transmission from a symptomatic male to his sexual partner have been documentedReference 11, including one male-to-male transmissionReference 12. Indeed, it is thought that viable virus might persist in semen for at least several weeks after it has been cleared from the bloodReference 7 Reference 10 Reference 9. Because the absolute probability of infection with ZIKV is considered low, so too is the likelihood of transmission via this route (Low likelihood, medium confidence). However, if a man does become infected with ZIKV, the likelihood of transmission to his sexual partner is assessed as Medium (low confidence). It is unknown if sexual transmission from asymptomatic but infected males to their partners is possible, or if infected females can transmit the virus to their partners.

Likelihood of local transmission in Canada

Here, we assess the likelihood of endemic or epidemic transmission of ZIKV in Canada. At the time of writing, there have been 55 confirmed cases of ZIKV in Canada, all resulting from travel to epidemic regions. Additional travel-associated cases are expected.

Local transmission would require the presence of a species of mosquito that can be infected with and transmit to human hosts ZIKV. Ae. aegypti is thought to be the principal vector in the current outbreak, with Ae. albopictus possibly playing a role. The distribution of Ae. aegypti is largely limited to tropical and subtropical areas and, while Ae. albopictus can occur in temperate regions, it also is limited by climateReference 23 Reference 39 Reference 40.

The likelihood that Ae. aegypti will become established in any area of Canada under current climatic conditions is estimated as Very Low (high confidence). This assessment is supported by a recent studyReference b Reference 23.

Ae. albopictus occurs in the United States, including the southern parts of some Eastern and upper Midwest states that border Canada. The likelihood that this species will become established in any area of Canada under current climatic conditions is considered Low (medium confidenceReference c). This assessment is based on recent work Reference 23 Reference 39 Reference 40 that estimated the current probability of this species occurring in most of Canada as at, or approaching, zero. However, one study did report that small areas in southern Ontario, southern Nova Scotia, as well as southern coastal British Columbia had low to moderate climatic suitability for this speciesReference 40.

Self-sustaining populations of the mosquitoes associated with the current ZIKV outbreak are not thought to occur in Canada. Based on the assumption of absence of Ae. aegypti, or absence of Ae. albopictus from all but a very few limited locations in Canada, there is Very Low likelihood (with high confidence) of epidemic spread and subsequent endemic establishment of ZIKV in Canada.

It is not known if mosquitoes that occur in Canada are capable of transmitting ZIKV nor, if they are, whether they could do so in their natural environment. However, the absence of reports of autochthonous transmission of ZIKV or other arboviruses associated with warm climates (e.g., dengue viruses, chikungunya virus) in Canada or similar climatic regions suggests that, even if native species could transmit ZIKV, they are very unlikely to support anything other than sporadic transmission (Very Low likelihood, high confidence).

Assumptions for assessments of likelihood of local transmission

We have made a number of assumptions in assessing the likelihood of local transmission:

  1. Populations of Ae. aegypti, are not established in Canada. This assumption is supported by a robust assessment of the distribution of this vector speciesReference 23.
  2. Populations of Ae. albopictus are not established in Canada, or occur with a geographic distribution too limited to support endemic transmission of ZIKV. This assumption is supported by robust assessments of the distribution and climatic suitability of CanadaReference 40 for this species as well as its absence (except for rare individual specimens in southeastern Canada) in recent mosquito surveillance for West Nile virus in Canada.
  3. Other mosquito species occurring in Canada are not capable of maintaining cycles of Zika virus transmission. This assumption is based upon the absence of records of ZIKV from northern temperate regions of the world Reference 41 Reference 42 Reference 43.
  4. There are temperature limitations to transmission of ZIKV (e.g., effects of temperature on the extrinsic incubation period in mosquitoes) that limit endemic transmission to tropical and sub-tropical areas. This assumption is based on similar limits on transmission of dengueReference 41 Reference 42 Reference 43 Reference 44 Reference 45 Reference 46.
  5. There are no alternative (i.e. non-mosquito-borne) routes of ZIKV transmission, including sexual transmissionReference d, capable of maintaining epidemic or endemic transmission cycles in Canada.

Likelihood of ZIKV infection for travellers

At the time of writing, many countries have reported recent, locally-acquired ZIKV cases. Continued spread of ZIKV is expectedReference 44 with the result that more areas will present a risk to Canadian travellers. To date, of approximately 2,750 individuals tested by the Canadian health care sector, 55 (~2%) have yielded positive results for ZIKV infection (personal communication, Dr. Theodore Kuschak, April 20 2016). All cases acquired ZIKV via recent travel to: Barbados (n=15), Brazil (n=2), Central America (Honduras, Panama, and Guatemala; n=1), Colombia (n=6), Costa Rica (n=1), Dominical Republic (n=2), El Salvador (n=7), Guyana (n=5), Haiti (n=9), Nicaragua (n=1), Saint Lucia (n=1), and Venezuela (n=1). Thus, among Canadians who have travelled to countries with active ZIKV transmission, the likelihood of infection is MediumReference e (with high confidence). However, only a small minority of Canadians who have travelled to areas of risk have been tested. Hence, the true prevalence of ZIKV infection among Canadian travellers is uncertain, but is likely substantially lower than the estimated 2% among individuals who have been tested to date.

Factors that could affect the likelihood or impact of infection

The impact of traveller- and/or itinerary-specific factors on the likelihood or impact of ZIKV infection has not been well described. However, there are a number of plausible relationships:

  • Conditions at higher elevations (≥ 2,000 m) are generally not supportive of viral replication in, or survival of, Ae. aegypti populations. Correspondingly, the relative likelihood of infection with ZIKV might be substantially lower for travellers (depending on how much time they spend at altitude compared to lower elevations) to such areas.
  • All else held equal, the likelihood of infection is higher in countries/areas that are reporting high levels of ZIKV activity compared to those that are not.
  • The likelihood of infection is likely lower for shorter travel durations and/or when staying in protected environments (e.g., well screened and air-conditioned accommodations, transiting through an airport in a risk area). This might also apply to situations where the traveller is staying in an isolated location, i.e. where there are relatively few residents who might support sustained transmission.
  • Travellers with co-morbidities (often, these are associated with age) might be at increased risk for more serious ZIKV-associated outcomes.

Impact of ZIKV infection

For most travellers, ZIKV will have little or no health impact (Low impact, with medium confidence). This is because infection will be relatively infrequent, and, of those infected, only about 20-25% will develop illness, most of it mildReference 25 Reference 29.

However, infection with ZIKV is a cause of rare but severe outcomes such as GBSReference 44. Indeed, cases of GBS and other neurological syndromes Reference 32 Reference 33 have been reported in 13 countries or territories affected by the current outbreakReference 31. Perhaps the most compelling evidence related to infection with ZIKV and GBS comes from a retrospective case-control study done with patients from French Polynesia ZIKV outbreak during 2013-2104Reference 30. Among the 42 GB cases, all but one (98%) showed serologic evidence (anti-ZIKV IgM and IgG) of ZIKV infection, compared to 35 of 98 (36%) matched controls (Odds Ratio 59.7, 95% Confidence Interval 10.4 to ∞). Based on an estimated ZIKV attack rate of 66% among the population of French Polynesia the authors estimate the proportion of post-ZIKV infection GBS as approximately 1 GBS case per 4,000 ZIKV infections. This estimate would put ZIKV among the higher-risk pathogens of those known to cause GBS, equal to or less than the risk posed by Campylobacter jejuni (1 to 2.6 GBS cases per 4,000 infectionsReference 48), and less than the risk posed by cytomegalovirus (2.4 to 8.8 GBS cases per 4,000 infectionsReference 49).

Again, for most infected travellers, ZIKV will have little or no health impact (Low impact, with medium confidence). Severe outcomes (e.g., GBS) might occur in some affected individuals (High impact, high confidence).

Impact of infection on unborn children of women who acquire ZIKV

There is now scientific consensus that ZIKV is a cause of infant microcephaly or other severe brain anomalies in children born to mothers infected during pregnancyReference 21 Reference 31. Evidence supporting this conclusion is well described in a recent recently publicationReference 21. However, the likelihood that prenatal ZIKV infection will cause foetal harms remains uncertain. There is some evidence that this might not be an infrequent occurrence. For example, during the French Polynesia outbreak, it was estimated that congenital abnormalities occurred in the developing foetus of approximately 1% of the time in mothers infected during the first trimesterReference 50.

In conclusion, ZIKV is now considered a cause of infant microcephaly or other severe brain anomalies. Substantial effort continues to be directed towards clarifying the effect of infection timing on fetal development, and determining if there are other contributing risk factors (e.g., nutritional status, or other environmental factors)Reference 51. Future scientific results could change this judgement substantially, but we estimate a Very High impact (with high confidence) on the unborn child of a woman who acquires ZIKV while pregnant.

Biosafety information for laboratory workers

ZIKV is classified as a Risk Group 2 human pathogen, since this virus presents a moderate individual risk and a low community risk. Laboratory work involving ZIKV requires Containment Level 2 physical and operational requirements as outlined in the Canadian Biosafety Standard. The impact on the unborn children of pregnant women working in the laboratory with ZIKV could be Very High (with medium confidence; see Impact section), if she became infected.

The main risks for laboratory acquired infection include accidental auto-inoculation and exposure to specimens from viremic patients, experimentally-infected animals, or ZIKV cultures. Local risk assessments should take into consideration the activities taking place in the laboratory to determine if risk reduction strategies in place are sufficient. Pregnant women or women trying to get pregnant should be made aware of the potential risks for the fetus and take extra care when working in a laboratory where ZIKV is propagated or handled.

Conclusions and Risk mitigation

In summary, we conclude that the overall risk of infection to Canadians (while in Canada) is very low. This is driven by the Very Low likelihood of exposure in Canada through mosquito-based transmission. An exception is transmission from symptomatic males to their sexual partner (Medium likelihood, with low confidence). The overall likelihood of infection for a Canadian travelling to an outbreak area is Low (medium confidence), and the impact for most of those infected will be Low (medium confidence). However, for some of those who are infected, impact may be High (high confidence) specifically because of the association with severe outcomes such as GBS. Although pregnant women or those who may soon become pregnant are assumed to be equally likely to be infected as are other travellers, the impact of such infection could be, for the unborn child, Very High (high confidence).

Persons considering travel should consult the Agency’s Travel Health Notice on ZIKV, and Canadian recommendations for the prevention and management of ZIKV-disease developed by the Committee to Advise on Tropical Medicine and Travel.

What can be anticipated in the next 6 months

The Agency continues to closely monitor the situation. Changes in scientific information are continually monitored, and this review will be updated on an as-needed basis.

References

Appendix 1 – Definition of technical terms

Table 1: Working definitions for likelihood levels
Level Definition
Very low Could occur only under exceptional circumstances
Low Could occur some of the time
Medium Will occur some of the time
High Is expected to occur in most circumstances

Table 2: Working definitions for impact levels
Level Impact
Very low Limited impact on the affected population
Few extra costs for authorities and stakeholders
Low Minor impact for a small population or at-risk group
Some increase in costs for stakeholders
Medium Moderate impact, as a large population or at-risk group is affected
Moderate increase in costs for stakeholders
High Major impact for a small population or at-risk group
Significant increase in costs for stakeholders
Very high Severe impact for a large population or at-risk group
Serious increase in costs for stakeholders

Table 3: Working definitions for confidence levels
Level Definition Examples of information/evidence
Low Little or poor-quality evidence, significant uncertainty, conflicting views amongst experts, no experience with similar incidents. Further research is likely to have significant impact on the results of the assessment.

Further research is very likely to change the results of the assessment and the confidence in the assessment and the information used.
Individual case reports

Grey literature

Individual, non-expert opinion
Medium Adequate quality of evidence, including consistent results, reliable source(s), and assumptions made on analogy. Agreement between experts or opinions of two trusted experts. Further research may necessitate some changes to the assessment.

Further research is likely to have an impact on the confidence in the assessment and information used. It may change the results of the assessment.
Non-peer-reviewed published studies/reports

Observational studies

Surveillance reports

Outbreak reports

Individual, expert opinion
High Good-quality evidence, multiple reliable sources, verified, multiple expert opinions concur, experience with previous and similar events. Further research is unlikely to change the results of the assessment.

Further research is unlikely to change the confidence in the assessment.
Peer-reviewed published studies where design and analysis reduce bias (i.e. systematic reviews, RCT, outbreak report).

Textbooks regarded as definitive sources.

Expert group risk assessment, or specialized expert knowledge, or consensus opinion of experts.
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