Communicable Diseases Network Australia

Interim recommendations for assessmentof pregnant women returning from Zika virus-affected areas

Date published: 18 February 2016

The recommendations for Zika virus testing may change as the outbreak evolves. Please return to this website to check the latest recommendations before testing.

Limited data from some recent outbreaks of Zika virus infectionin Central and South America, particularly Brazil, have raised concerns that infection with Zika virus in pregnant women might cause certain congenital abnormalities (including microcephaly). The evidence for a causal link between Zika virusinfection and these outcomes is evolving and further studies are required. While it is not possible at the current time to quantify the risk to the unborn baby of a person infected with Zika virus, given the current uncertainty and the observed association between Zika virus infection in pregnancy and congenital abnormalities, the following recommendations for testing and follow up are being made in order to manage any risk. These recommendations will be updated as more information becomes available about the nature of the risk.

Healthcare providers should inquire about travel history among all pregnant women. Those with a positive history of travel to a Zika virus-affected country during or immediately prior to pregnancy should be evaluated(refer to the list of countries at the Department of Health website).

Counselling of pregnant women who have travelled to Zika virus-affected areas is not straightforward. The available testsfor Zika virus infection may require 4 weeks following the last potential exposure to give a result and for some, will not provide complete reassurance that they have not had a Zika virus infection. There is no specific treatment for Zika virus if a positive test is returned. A positive test in the mother gives no information on whether the fetus is infected or harmed.

Symptomatic pregnant women

Testing should be offered to symptomatic pregnant women (current or past). A complete check for travel related illnesses compatible with symptoms of Zika virus infection is advised in addition to testing for Zika virus.

Symptoms compatible with Zika virusinfection may include a low-grade fever, arthralgia (notably of small joints of hands and feet, with possible swollen joints), myalgia, headache, retro-ocular headaches, conjunctivitis, cutaneous maculopapular rash, and post-infection asthenia. These overlap with other arboviral illnesses such as dengue and chikungunya, although Zika virusinfection usually has a milder clinical course. Malaria may be another potential differential diagnosis in returned travellers from certain regions. In a symptomatic pregnant woman, it is recommended to seek specialist infectious disease advice to discuss the possible range of differential diagnoses.

Asymptomatic pregnant women

Testing of asymptomatic pregnant women with a history of potential exposure to Zika virus can be more difficult to interpret. A detailed history should be taken to assess the risk of exposure, which would include the dates and duration of travel, knowledge of any local transmission in the areaand exposure to mosquito bites. There is a low chance of the disease being present in this population. Testing risks false positive results and this needs to be discussed with the pregnant woman.

To assist in interpretation of results, specimens should be collected at the time of the initial consultation for all pregnant women who have recently returned from a Zika virus-affected area. For asymptomatic women who present less than 2 weeks following their last potential exposure, these baseline samples should be held at the laboratory for later reference if required.

For guidance on obstetric management including ultrasound surveillance please refer to the RANZCOG guideline.

Table: Overview of recommendations for assessment of pregnant women returning from Zika virus-affected areas.

Time of exposure / Clinical illness^ / Acute specimens and testing to request / Results of first test / Repeat testing to be at least 2 weeks after first sample and at least 4 weeks following last potential exposure / Results of second serological test / Obstetric Follow-up
Last potential exposure within the last 2 weeks / Symptomatic / PCR (blood and urine) and serology for suspected Zika virus / Negative PCR for Zika virus#
Negative serology / Serology for suspected Zika virus infection / Zika virus positive or indeterminate
For indeterminate serology result repeat serology in 2 weeks / Refer for obstetric specialist counselling and advice e.g. MFM if available
Zika virus negative / Provide routine pregnancy care
Negative PCR for Zika virus#, Positive or indeterminate serology / Further testing will be performed by the lab
Repeat serology for suspected Zika virus infection / Zika viruspositive or indeterminate / Refer for obstetric specialist counselling and advice e.g. MFM if available, after first serology test. Discuss results with pathologist. Review when further serology completed
Zika virusnegative / Provide routine pregnancy care*
Positive PCR#,
Positive or Negative serology / Serology for suspected Zika virus infection for confirmation / Do not wait for serology results; refer on receipt of initial positive results. / Refer for obstetric specialist counselling and advicee.g. MFM if available. Review when further serology completed.
Asymptomatic / PCR and serology for suspected Zika virus and stored for later analysis (acute phase samples) / Not applicable – hold only* / Serology for suspected Zika virus infection
If positive, the laboratory will test the acute phase samples. / Zika viruspositive or indeterminate / Discuss results with Pathologist and refer for obstetric specialist counselling and advice e.g. MFM if available
Zika virusnegative / Provide routine pregnancy care
Last potential exposure more than 4 weeks ago / Asymptomatic or symptomatic in past / Serology for suspected Zika virusinfection / Zika virusNegative / Not required / Provide routine pregnancy care
Zika virusPositive or indeterminate / Consider repeating serology 2 weeks after the first sample / Do not wait for second serology results; refer on receipt of first results. / Refer for obstetric specialist counselling and advice e.g. MFM if available. Discuss with pathologist.
Last potential exposure 24weeks ago / Asymptomatic or symptomatic in past / Serology for suspected Zika virus infection
PCR Urine / Zika viruspositive or indeterminate / Consider repeating serology 2 weeks after the first sample / Do not wait for second serology results; refer on receipt of first results. / Refer for obstetric specialist counselling and advice e.g. MFM if available. Discuss results with pathologist.
Zika virusnegative / Repeat serologyfor suspected Zika virus infection / Zika viruspositive or indeterminate / Refer for obstetric specialist counselling and advice e.g. MFM if available. Discuss results with pathologist
Zika virusnegative / Provide routine antenatal care.

Notes:

MFM = maternal fetal medicine unit.
Specialist obstetric advice and management- see RANZCOG guideline LINK.
#Repeat serum samples should be collected at least 2 weeks after the previous sample and at least 4 weeks after the last possible exposure to allow for antibody development and a rising titre to be detected.
^ Symptoms compatible with Zika virus infection may include a low-grade fever arthralgia(notably of small joints of hands and feet, with possible swollen joints), myalgia, headache, retro-ocular headaches, conjunctivitis, cutaneous maculopapular rash, post-infection asthenia which seems to be frequent.
*Where jurisdictions have capacity, additional testing may be performed
If an alternative diagnosis is confirmed this should be managed as appropriate.
No ZIKV assays, PCR or serology, are currently validated to guide management of pregnant women, and results must be interpreted cautiously together with all available clinical & laboratory data.

#Repeat samples should be collected at least 2 weeks after the previous sample and at least 4 weeks after the last possible exposure to allow for antibody development and a rising titre to be detected.

* Possible further investigations include repeat serology, serial ultrasounds, and amniocentesis

^Referral for obstetric evaluation and further testing if any abnormalities on ultrasound.

+One month prior to the approximate time of conception.

Samples from asymptomatic pregnant women with recent exposure to Zika virus will be held until the second serological sample is tested. At that time, further testing on the acute sample will be performed if required.

When ordering testing for Zika virus, please order:

Relevant Zika virus testing according to the guidelines
Additional testing as required. (e.g. dengue,chikungunya and other relevant infections, FBC).

Additional information to assist the pathologist may include:

Country or countries visited
Dates of travel (arrival and departure in each country)
Relevant symptoms and date of onset/cessation
History (including approximate dates) of receiving any flavivirus vaccine ( e.g. Japanese encephalitis, yellow fever) or previous flavivirus illness (e.g. West Nile virus, dengue)
Pregnancy status – yes, no, unknown
If testing follows abnormal ultrasound , describe findings (normal, microcephaly suspected, CNS calcification)
Other information that you believe may help the pathologist.