For health professionals: Zika virus infection

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What health professionals need to know about the Zika virus

The Zika virus is a neurotropic virus that is capable of entering the nervous system and targets neural progenitor cells. The Zika virus is transmitted primarily as a mosquito-borne infection; it can also be transmitted sexually.

Exposure to the Zika virus during fetal development increases the risk of severe health outcomes, such as Congenital Zika Syndrome. For this reason, travellers to Zika affected countries or areas should wait before trying to conceive:

  • 6 months after returning, if you are a man, regardless of whether your female partner travelled with you.
  • 2 months after you return, if you are a woman and your male partner did not travel with you.
  • Couples should practice abstinence or use barrier methods, for example, using condoms correctly.

Male travellers who have a pregnant partner should:

  • always use a condom correctly, or
  • avoid having sex for the duration of the pregnancy

To help advise your patients who are planning to travel, you may want to:

For additional detail, review CATMAT’s Zika Virus Prevention and Treatment Recommendations.

Agent of disease

The Zika virus is a single stranded RNA flavivirus and a member of the Flaviviridae family.

There are at least 2 Zika virus lineages which are the:

  • Asian lineage
  • African lineage

A recent study suggests there may be three geographically distinct viral lineages (African I and II, and Asian), however much is still unknown about the evolution and diversity of Zika virus. The Asian lineage strain has recently emerged in the Pacific and the Americas.

Aedes aegypti is:

  • the primary vector of Zika virus
  • largely restricted to tropical and subtropical regions, though temperate populations may occur in isolated refuges

Aedes albopictus has been implicated as a vector, though its role in the current outbreak is uncertain. This species is widely present outside the tropics.

A small number of the Aedes aegypti and Aedes albopictus species have recently been found in Windsor, Ontario. It is not known whether populations of these species have become established in Windsor. Studies are on-going to define the risk from the recent introduction of these two mosquito species into this part of Ontario.

Currently, the mosquitoes that transmit the Zika virus are not established in Canada due to the climate. So, there is a very low probability of mosquito transmission in Canada.

These two species of mosquito are the same type of mosquito that can carry and transmit dengue virus and chikungunya virus.

The Zika virus is in the same family of viruses that cause:

  • dengue
  • West Nile
  • St. Louis encephalitis
  • Japanese encephalitis

Clinical manifestations

Asymptomatic infections are common. Only 1 in 4 people infected with Zika virus are believed to develop symptoms.

The main symptoms of Zika virus infection include:

  • retro-orbital pain
  • low-grade fever (37.8 to 38.5°C)
  • general non-specific symptoms, such as:
    • myalgia
    • asthenia
    • headaches
  • transient arthritis or arthralgia with possible joint swelling
    • mainly in the smaller joints of the hands and feet
  • maculopapular rash often spreading from the face to the body
  • conjunctival hyperaemia or bilateral non-purulent conjunctivitis

The incubation period ranges from 3 to 14 days. The symptoms are usually mild and last for 2 to 7 days. Most people recover fully without severe complications and only require simple supportive care. Hospitalization rates are low.

Infection may go unrecognized or be misdiagnosed as:

  • dengue
  • chikungunya
  • other viral infections causing fever and rash

Spectrum of clinical illness

Congenital Zika Syndrome involves a spectrum of neurological and other developmental deficits, including but not limited to:

  • hearing loss
  • club foot and arthrogryposis
  • abnormal brain development including:
    • microcephaly
    • cerebral atrophy
    • callosal hypoplasia
    • diffuse subcortical calcification
    • abnormal cortical development
  • vision impairment and ocular anomalies such as:
    • cataracts
    • micropthamia
    • retinal abnormalities
  • other neurologic abnormalities including:
    • seizures
    • spasticity
    • irritability

A number of countries have reported a correlation between infection with the Zika virus the development of Guillain-Barré Syndrome (GBS). This is being further investigated through research studies.

A small number of deaths associated with Zika virus infection have been reported. These are being observed in:

  • infants with severe congenital anomalies
  • older adults with multiple comorbidities

Birth defects were reported in similar proportions of fetuses/infants whose mothers did and did not report symptoms during pregnancy. Defects were reported among all trimesters, although there was a higher likelihood if the mother was infected during the first trimester.

Recent findings from the US Zika Pregnancy registry (United States and United States Territories) found that approximately 1 in 20 fetuses or infants whose mothers had Zika virus infection during pregnancy had congenital anomalies.

When analysis was restricted to confirmed Zika virus infections in the first trimester, approximately 1 in 10 fetuses or infants had a possible Zika virus-associated congenital anomaly.

Testing

The decision to offer Zika testing to adults is described in the decision-tree for Zika virus laboratory testing.

Decisions to test should consider:

  • travel history
  • populations at risk
  • presence of symptoms consistent with Zika virus infection
  • possible non-travel related exposures, for example, sexual transmission

The choice of the optimal test, including timing and modality, are explained more fully in the diagnostics section.

The workup for potential Zika virus infection in pediatric patients, particularly infants born to mothers affected in pregnancy, can involve some additional non-laboratory testing.

Please refer to the Canadian Paediatric Society “Practice Point”, March 30, 2017 for guidance.

Decision-tree for Zika Virus Laboratory Testing

Text equivalent

This image is a decision-tree intended to help health care providers make decisions related to Zika virus laboratory testing.

Male or non-pregnant female patient

1. The first question relates to the risk population: is the patient male or female?

If the patient is male or a non-pregnant female

2. Do they have a travel history or a sexual partner with a travel history to a place reporting local mosquito-borne transmission of Zika virus infection?

If the answer is "no," testing for Zika virus infection is not recommended. Zika virus infection is unlikely without travel or exposure history.

Other infectious diseases with similar signs and symptoms are possible. Additional infectious diseases work-up may be warranted. If unsure about the relevance or scope of work-up, consider consulting with an infectious diseases specialist.

2. If the answer is "yes" for travel history for the male or non-pregnant female, choose from 3 options:

  • "The patient is experiencing acute symptoms consistent with Zika virus infection."
  • "The patient was previously symptomatic consistent with Zika virus infection and the symptoms have now resolved."
  • "The patient has had no symptoms consistent with Zika virus infection."

If the answer is "yes" for travel history for the male or non-pregnant female and:

2.A  that patient is experiencing acute symptoms consistent with Zika virus infection, testing is recommended.

If the answer is "yes" for travel history for the male or non-pregnant female and:

2.B  the patient was previously symptomatic consistent with Zika virus infection and the symptoms have now resolved, testing should be considered if a confirmed diagnosis would be helpful.

In some instances, such as couples trying to conceive where pregnancy cannot be delayed for medical reasons, testing may be warranted. In such cases, we recommend consulting with an infectious diseases specialist.

If the answer is "yes" for travel history for the male or non-pregnant female and:

2.C  if the patient has had no symptoms consistent with a Zika virus infection, testing is not routinely recommended.

As with the previous example, some individual cases may warrant testing. We recommend consulting with an infectious diseases specialist.

Decision-tree for Zika Virus Laboratory Testing

Text equivalent

Pregnant female patient

If the patient is a pregnant female

1. Does she have a travel history or a sexual partner with travel history to a place reporting local mosquito-borne transmission of Zika virus infection?

If the answer is “no”, then testing for Zika virus infection is not recommended. Zika virus infection is unlikely without travel or exposure history.

Other infectious diseases with similar signs and symptoms are possible. Additional infectious diseases work-up may be warranted. If unsure about the relevance or scope of work up, consider consulting with an infectious diseases specialist.

2. If the answer is “yes” for travel history or a sexual partner with travel history to a place reporting local mosquito-borne transmission of Zika virus infection for the pregnant female, choose from 3 options:

  1. “The patient is experiencing acute symptoms consistent with Zika virus infection.”
  2. “The patient was previously symptomatic consistent with Zika virus infection and the symptoms have now resolved.”
  3. “The patient has had no symptoms consistent with Zika virus infection.”

If the patient is a pregnant female and the answer is “yes” for travel history or a sexual partner with a travel history to a place reporting local mosquito-borne transmission of Zika virus infection and:

2.A  the patient is experiencing acute symptoms consistent with Zika virus infection, testing is recommended.

If the patient is a pregnant female and the answer is “yes” for travel history or sexual partner with travel history to a place reporting local mosquito-borne transmission of Zika virus infection and:

2.B  if the patient was previously symptomatic consistent with Zika virus infection and the symptoms have now resolved, testing is recommended.

If the patient is a pregnant female and the answer is “yes” for travel history or sexual partner with travel history to a place reporting local mosquito-borne transmission of Zika virus infection and:

2.C if the patient has had no symptoms consistent with a Zika virus infection, testing is a consideration.

The absence of symptoms does not predict risk of Congenital Zika Syndrome. Due to the complexity of interpretation and timelines of pregnancy, you should consult early with an infectious diseases specialist before testing is considered.

Diagnosis

Laboratory diagnosis is usually accomplished by testing serum or plasma to detect any of the following:

  • viral genetic material (ribonucleic acid, RNA)
  • virus-specific antibodies produced by the body

There are 2 testing methods available for detecting Zika virus: polymerase chain reaction (PCR) testing and serology testing.

Polymerase chain reaction (PCR) testing

This test directly detects the genetic material of the Zika virus. A positive result confirms the patient has a Zika virus infection.

The PCR assay is most effective when testing clinical specimens such as:

  • blood collected within 10 days of start of symptoms
  • urine collected within 14 days of start of symptoms

The major limitation of this test is that Zika virus may only be present in these types of specimens for a short time after the start of an infection.

Serology testing

Instead of testing for components of the virus, these tests are able to detect the presence of Zika virus antibodies. Antibodies become detectable approximately one week post-symptom onset.

The major advantage of a serology test is that it remains positive for several months or longer after infection.

The major limitations are that it:

  • may take several days or weeks to perform and report back results
  • is prone to cross-react with antibodies that target other similar flaviviruses related to Zika virus, including the dengue virus. A positive result may represent a previous exposure to another virus or a past vaccination for viruses such as yellow fever, making interpretation difficult.

Testing considerations

PCR and serology tests, if positive, can be used to confirm a Zika virus infection.

PCR

A positive PCR test for Zika virus signifies an acute infection despite mild symptoms.

A negative PCR test for Zika virus may mean:

  • there was no infection
  • the individual was infected but the virus was no longer present when the sample was collected. Subsequent serological testing is recommended to confirm a case.

Serology

An initial positive serological result may represent:

  • an acute infection or previous exposure to Zika virus
  • an acute infection or previous exposure to another flavivirus
  • past vaccination for other viruses, such as yellow fever

Identifying and confirming Zika virus-specific antibodies in serum samples may require further testing and, in some cases, collecting additional samples. This is due to possible cross-reactivity of serologic tests with antibodies that relate to other similar flaviviruses such as dengue virus.

A negative serological test for Zika could mean:

  1. antibodies have yet to develop
  2. there was no infection, which may warrant the collection of additional samples

A negative serology test performed 1 to 2 months following return from travel would indicate that there was no infection, because antibodies usually develop within 4 weeks following exposure. If the health care provider suspects the test was performed too early, a second blood sample may be collected for additional testing.

Patients should be aware of these test limitations and accept that results may not be available for a number of weeks.

Treatment

Currently, there is no prophylaxis, vaccine or treatment for Zika virus infection. Treatment may be directed toward symptom relief, such as:

  • rest
  • fluids
  • analgesics
    • avoid acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs until dengue infection has been eliminated as a possibility
  • antipyretics

Surveillance in Canada

The Public Health Agency of Canada and provincial and territorial partners work closely to conduct national surveillance on Zika virus cases in Canada.

Health professionals in Canada play a critical role in identifying cases of Zika virus infection. Health professionals who have questions should contact their local public health authorities for further details.

The National Microbiology Laboratory performs testing to detect the virus and offers testing support to provinces and territories. Some provincial laboratories also offer testing.

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