Zika virus: A summary

What is Zika?
Zika virus is a flavivirus from the same family as dengue virus and West Nile virus. Infection in humans was rare and isolated to Africa and Asia until 2007.[1-3] Since the first human case of Zika infection in the western hemisphere was reported in 2015,[3] the virus has caused widespread outbreaks across Central and South America, Mexico, and the Caribbean.

How and where it is acquired
Transmission of Zika virus is via the Aedes mosquito, which is found in tropical, subtropical, and some temperate regions.[4,5] There have also been rare accounts of transmission by sexual contact and through blood transfusion in countries outside of Canada.[6-8] There has been no transmission of Zika within Canada to date, and none is expected due to the absence of an appropriate vector.[4,5] An updated list of countries with known Zika virus circulation (Figure 1) can be found on the Centers for Disease Control and Prevention website (www.cdc.gov/zika/geo/index.html).

Signs and symptoms of infection
Only 20% to 25% of those infected with Zika virus develop symptoms.[3,9,10] These include fever, maculopapular rash, arthralgias, nonpurulent conjunctivitis, headaches, and myalgia.[3,9] The incubation period is between 3 and 12 days, and the illness lasts between 2 and 7 days.[3,10,11] Most patients recover fully without complications, although there are some worrisome associations under investigation.[2,10]

Associations with GBS and microcephaly
A relationship between Zika infection and Guillain-Barré syndrome (GBS) has been suggested due to higher-than-usual rates of GBS observed in French Polynesia, Brazil, and El Salvador during recent outbreaks.[11-14] Research into this association is ongoing.

Zika virus infection has also been linked to congenital abnormalities, specifically microcephaly. Brazilian states with known Zika transmission have reported a greater than twentyfold increase in rates of children born with microcephaly since the outbreak began.[3,15] A recent case report of vertical Zika transmission identified viral RNA in the brain tissue of a fetus with severe microcephaly.[16] Other case reports have identified Zika RNA and antibodies in the amniotic fluid of microcephalic fetuses from affected areas in Brazil.[17,18] Although these findings do not prove causality between Zika virus infection and microcephaly, the link is now strongly supported by mounting epidemiologic and clinical data.

Preventive measures
Given the potential impact of Zika virus, pregnant women and women trying to become pregnant should discuss all travel plans with their health care provider to assess their risk for Zika exposure and should consider postponing travel to areas of known Zika circulation.[19]

Based on the current understanding of the Zika incubation period, duration of viremia, and unclear duration of persistence in tissues, the Public Health Agency of Canada recommends that women returning from areas of known Zika circulation should avoid becoming pregnant for at least 2 months following their last potential exposure.[19]

Of concern to male travelers, there is evidence that Zika virus can persist in semen for more than 2 weeks.[19] Total duration of viral shedding in male and female genital secretions is currently unknown, although experience with similar viral infections suggests that viral shedding can be very prolonged.[19] As a precaution, men with partners who are pregnant or who could become pregnant should abstain from sexual activity or consistently and correctly use condoms for at least 2 months following return from areas of known Zika circulation.[19] It is reasonable to consider condom use for the duration of the pregnancy until more is known about sexual transmission of the virus.[19]

All travelers should take strict steps to avoid mosquito bites at all times of the day and night. This includes covering up, using insect repellent on exposed skin, and protecting living and sleeping areas from mosquito entry.[19,20] More information can be found on the Public Health Agency of Canada website (www.publichealth.gc.ca).[20]

How and when to order testing
Testing for Zika virus RNA and serology is available through the BCCDC Public Health Laboratory (Figure 2). Viral RNA detection via PCR is the most effective means of detecting the virus; however, it is only positive in blood samples for up to 7 days from symptom onset. Urine samples can be positive for Zika virus RNA for more than 10 days.[19,21] Zika virus antibodies (serology) are detectable approximately 1 week after the start of symptoms and the test remains positive for several months. Zika serology is the test of choice for asymptomatic patients. While it is quick to perform, Zika serology is prone to cross-reactivity and confirmatory testing requires additional time.[19] Details regarding sample collection can be obtained from the BCCDC Public Health Laboratory (www.bccdc.ca/health-professionals/professional-resources/laboratory-services).

Testing should be limited to travelers returning from Zika-affected areas and their female partners. All symptomatic patients with onset of Zika-like symptoms abroad or within 14 days of return should be offered both viral and serologic testing as part of a workup for fever in a returning traveler. Testing should also be offered to asymptomatic pregnant women with a history of Zika-like illness while abroad or shortly following their return, as well as those whose fetus is suspected of having a congenital abnormality.[19] In pregnant women and those who become pregnant within 2 months of return with no history of Zika-like symptoms, testing should be assessed on a case-by-case basis.[19] These patients should be counseled on the risks of Zika infection, pregnancy options including termination, and sensitivity, specificity, and turnaround time of current diagnostic testing.[19] The decision to test these patients should be based on how the results will be used. Testing is not recommended for other asymptomatic travelers.[19,21]

It is recommended that all exposed pregnant women undergo serial monitoring by ultrasound with close attention to cranial measurement trends over time. Unfortunately, ultrasound cannot reliably detect microcephaly until late in the second trimester, and there is no gestational age by which microcephaly can be ruled out.[19]

Referral of exposed pregnancies
Referral to the Reproductive Infectious Diseases Clinic at BC Women’s Hospital (tel: 604 875-2160, fax: 604 875-2871) is recommended for pregnant women returning from a Zika-affected area who have a positive test for Zika virus infection or an ultrasound showing an abnormality consistent with congenital viral infection.[22]

Sample case
A 30-year-old woman presents to her family doctor’s office after returning from a vacation to South America with her husband. She left on her trip 4 weeks ago and is currently 12 weeks pregnant. She has heard news of recent outbreaks of Zika virus in South America and its links to congenital abnormalities. She is concerned that her pregnancy might be affected.

The patient notes that she and her husband did get a few mosquito bites while in Brazil, but denies any history of illness while abroad and currently feels well. She and her husband have not had sex since their return 5 days ago. Her family doctor counsels her on the available testing methods and the use of condoms with her husband for at least 2 months. The patient requests to be tested for Zika virus as it will impact her decisions regarding her pregnancy, and Zika virus serology is ordered. Her family doctor also arranges for serial ultrasounds for fetal monitoring. 

The bottom line
Recent outbreaks of the mosquito-borne Zika virus pose a new risk to travelers to the Caribbean, Mexico, and Central and South America. Given the lack of suitable vector in Canada, the risk to most Canadians is low. There is concerning data linking Zika virus infection with GBS and microcephaly, warranting vigilant prevention and screening measures for travelers to Zika-affected areas, particular pregnant women.

Zika virus disease is still largely a condition of poverty that is thriving in an at-risk climate. In many countries affected by the recent outbreaks, access to mosquito precautions, contraception, and abortion services is very limited if available, putting women of childbearing age at particularly high risk. In addition to vigilant screening measures for Canadian travelers, we can contribute to the global effort to control this outbreak by supporting Zika virus research here in Canada and by providing laboratory, surveillance, and logistical support to those countries most affected.
—Andrew Hurlburt, MD 
PGY-2 Internal Medicine, UBC
—James Brooks, MD, FRCPC
BCCDC
—Deborah Money, MD, FRCSC
Department of Obstetrics and Gynaecology, UBC
—David Patrick, MD, FRCPC, MHSc 
BCCDC 
School of Population and Public Health, UBC

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This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.


References

1.    Dick GW, Kitchen SF, Haddow AJ. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 1952;46:509-520.
2.    Duffy MR, Chen T-H, WT Hancock, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009;360:2536-2543. 
3.    Public Health Agency of Canada. Rapid risk assessment: The risk of Zika virus to Canadians. 19 February 2016. www.healthycanadians.gc.ca/publications/diseases-conditions-maladies-aff....
4.    Lima A, Lovin DD, Hickner PV, et al. Evidence for an overwintering population of Aedes aegypti in Capitol Hill Neighborhood, Washington, DC. Am J Trop Med Hyg 2016;94:231-235.
5.    Kraemer MU, Sinka ME, Duda KA, et al. The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus. Elife 2015;4:e08347.
6.    Musso D, Roche C, Robin E, et al. Potential sexual transmission of Zika virus. Emerg Infect Dis 2015;21:359-361.
7.    Aubry M, Finke J, Teissier A, et al. Seroprevalence of arboviruses among blood donors in French Polynesia, 2011-2013. December. Int J Infect Dis 2015;41:11-12.
8.    Musso D, Nhan T, Robin E, et. al. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014. Euro Surveill 2014;19:pii: 20761.
9.    European Centre for Disease Prevention and Control. Zika virus infection: Factsheet for health professionals. Accessed 19 February 2016. http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/factsheet-hea....
10.    Ioos S, Mallet HP, Leparc GI, et al. Current Zika virus epidemiology and recent epidemics. Med Mal Infect 2014;44:302-307.
11.    European Centre for Disease Prevention and Control. Rapid risk assessment—Zika virus epidemic in the Americas: Potential association with microcephaly and Guillain-Barré syndrome. Accessed 19 February 2016. http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-a....
12.    Oehler E, Watrin L, Larre P, et al. Zika virus infection complicated by Guillain-Barré syndrome—case report, French Polynesia, December 2013. Euro Surveill 2014;19:pii 20720.
13.    Pan American Health Organization/World Health Organization. Epidemiological update: Neurological syndrome, congenital anomalies, and Zika virus infection. Accessed 19 February 2016. www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid....
14.    Pan American Health Organization/World Health Organization. Epidemiological alert: Neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas. Accessed 19 February 2016. www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid...
15.    Brazil Ministry of Health. The public health Emergency Operations Center report on microcephaly. Epidemiological week 1 of 2016 (in Portuguese). Accessed 14 March 2016. http://portalsaude.saude.gov.br/images/pdf/2016/janeiro/13/COES-Microcef....
16.    Mlakar J, Korva M, Tul N, et al. Zika virus associated with microcephaly. N Engl J Med 2016 [Epub ahead of print].
17.    Calvet G, Aguiar RS, Melo AS, et al. Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: A case study. Lancet Infect Dis 2016;pii:S1473-3099(16)00095-5 [Epub ahead of print].
18.    Oliveira Melo AS, Malinger G, Ximenes R, et al. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: Tip of the iceberg? Ultrasound Obstet Gynecol 2016;47:6-7.
19.    Public Health Agency of Canada. Canadian recommendations on the prevention and treatment of Zika virus. Accessed 29 February 2016. www.healthycanadians.gc.ca/publications/diseases-conditions-maladies-aff....
20.    Public Health Agency of Canada. Insect bite prevention. Accessed 19 February 2016. http://travel.gc.ca/travelling/health-safety/insect-bite.
21.    Public Health Agency of Canada. Laboratory testing recommendations for Zika virus. Accessed 19 February 2016. http://healthycanadians.gc.ca/publications/diseases-conditions-maladies-....
22.    Vancouver Coastal Health. Community medicine newsletter: Zika virus update. Accessed19 February 2016. https://gallery.mailchimp.com/05d96aedd1e1ddd5ab1791b58/files/Comm_Med_N....

Andrew Hurlburt, MD, David Brooks, MD,, Deborah M. Money, MD, FRCSC, David M. Patrick, MD, FRCPC, MHSc. Zika virus: A summary. BCMJ, Vol. 58, No. 3, April, 2016, Page(s) 158-161 - BCCDC.



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