Zika virus: management of infection and risk

The risk of congenital abnormalities is poorly characterised

The risk of Zika virus infection to a developing fetus is not fully understood. The recent rise in such infections has coincided with an apparent increase in birth defects—predominantly microcephaly but also ventriculomegaly, cell migration abnormalities, congenital contractures, stillbirth, and neonatal death.2 5 These abnormalities have largely been described in case reports and case series. A direct causal link has not been confirmed, but there is evidence of Zika virus infection in placentas of aborted fetuses and in the brains of babies with microcephaly who died soon after birth.6 7 If causality is established, further data will be needed before we could tell a pregnant woman how likely it is that she would have an affected child.

Preliminary data from a small case series suggest that infection in the early stages of pregnancy may pose the greatest risk,5 consistent with other viral infections such as rubella. No treatment is presently available to correct or alter the chances of adverse fetal outcomes.

Testing and monitoring of pregnant women is guided by symptoms

There is an absence of good evidence to guide testing and monitoring. However, expert guidance has been issued by international bodies.

Figure 1⇓ shows UK guidance for pregnant women who have travelled to an area with known Zika virus transmission during the pregnancy.1 In essence, all pregnant women who have travelled to an area affected by Zika virus should be offered a baseline fetal ultrasound scan and should be discussed with a secondary care obstetric team. If the ultrasound is normal, offer scans every four weeks throughout the pregnancy. Microcephaly and the other neurological abnormalities described may not become apparent on scans until after 20 weeks’ gestation or into the third trimester. Logistically, testing and care may be led by obstetric teams or form part of joint care with midwives or primary care doctors.

Fig 1 Algorithm for assessing pregnant women exposed to Zika virus1

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Detection of any neurological abnormalities, such as a small head (more than two standard deviations below the mean for gestational age) or intracranial calcifications, warrants referral to a fetal medicine unit for further investigation. Here, alternative causes of microcephaly—such as other congenital infections, chromosomal abnormalities and undefined genetic syndromes, exposure to teratogenic substances, and maternal metabolic diseases—will also be considered.

Pregnant women who present with clinical symptoms compatible with Zika virus infection (see box 3) while in, or within two weeks of return from, a Zika virus affected area should be considered for testing for Zika virus infection and other travel associated diseases relevant to the country of travel. Those who are asymptomatic but have just returned should be advised to seek medical care if they develop any symptoms consistent with Zika virus within the next two weeks.

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Interpreting tests for Zika virus is complicated

All patients undergoing testing for Zika virus infection should be discussed with infection specialists and the optimum testing strategy for this and any other infections agreed. The first line test and definitive diagnosis is made by identification of Zika virus RNA by means of PCR (polymerase chain reaction). This may remain detectable in blood for the first five days of infection and probably for up to two weeks in urine.8 Use the test in those with current or recent symptoms in liaison with the local virology laboratory. (In the UK this is generally serum and an EDTA blood sample, and also urine in sterile container if the patient is pregnant.)

If Zika virus RNA is detected, UK guidance suggests that the woman is offered direct referral to fetal medicine specialists. However, a negative PCR result cannot exclude infection (especially if the sample is sent several days after the onset of any symptoms), and follow-up with screening ultrasound scans at four-weekly intervals should be offered in this situation.

The United States uses a Zika virus IgM assay, and Australia is using IgM and IgG assays in an attempt to detect infections, including in those outside the testing window for viral RNA. The US Centers for Disease Control and Prevention advocates that all pregnant women returning from affected areas should be tested for Zika virus,9 with PCR tests if symptomatic and serological tests if asymptomatic.

The sensitivity, specificity, and applications of such serological tests (IgG or IgM) are not established, however. They are not currently advocated in the UK, although storage of a serum sample for potential future testing (once assays have been established and validated) may be suggested.

Amniotic fluid, if sampled, may also be tested by PCR, but the utility of such testing is not firmly established at present.

Discuss all those with symptoms and relevant travel history with local infection specialists

It is estimated that four out of five people with Zika virus infection are asymptomatic, and in those who do develop symptoms these are often non-specific (box 3). It is therefore important that the case of a symptomatic individual, such as described above, is discussed with a local infection specialist to allow assessment for other potential infections such as malaria and dengue.

Zika infection is not a notifiable disease in the UK, but it is in other countries such as the US and Australia.

Zika is transmitted via a type of mosquito but possibly also by semen or blood products

There is no need to avoid work or other activities of daily living. Zika virus is transmitted from human to human via a vector, the Aedes mosquitoes. These mosquitoes are not present in the UK, northern Europe, Canada, northwestern United States, Russia, northeastern Asia, and southern Australia, but they are widespread throughout much of the rest of the world.

It is possible that Zika virus may pass from human to human via other routes. There is a theoretical risk of transmission via infected blood or blood products.10 The virus has been identified in semen from two men infected with Zika virus,11 12 and, to date, there have been two reported instances of sexual transmission by male travellers to their partners in non-endemic areas (only one of these cases is presently published13). It is not known how long after infection the virus is detectable, or potentially infectious, in semen. There is no evidence of sexual transmission from women to men.

UK and European guidance advises that men with suspected or confirmed infection should use condoms with their partners (if pregnant or at risk of pregnancy) for six months.1 2 Abstaining would be another option. The US advises abstaining or using condoms for the duration of the pregnancy if the partner is pregnant, but does not specify a time period if they are not.14

For men who have been asymptomatic during travel in affected areas and for two weeks after return, UK and European guidance suggests that they consider using condoms for 28 days after their return if their partner is pregnant or at risk of pregnancy.1 2 The US guidelines do not specify a time period for asymptomatic men. The current advice is that condoms should be used for vaginal, oral, and anal sex. This should be discussed with patients.

These time periods are poorly evidence based. The 28 day window has been suggested to allow a 14 day incubation period and a 14 day viraemic period, even in asymptomatic people. The six month window may change once longer term data on seminal carriage is established.

Patients planning to donate blood, tissue, or semen should declare recent travel to affected areas (and Zika virus test results where known) before donation.

Risk to future pregnancies is unknown

There are few data to support advice on the duration of risk after potential exposure, but guidance has been issued. There is consensus across UK,1 European,2 US,3 and Australian15 guidance that women of childbearing potential who are travelling to Zika affected areas should ensure they are using reliable contraception and should avoid conceiving. Women who are pregnant should be strongly advised to avoid such travel if possible.

On return from endemic areas, advice in the UK is to avoid becoming pregnant for a further 28 days.1 It is thought, though with little evidence, that a fetus conceived after a woman has cleared the virus would not be at risk of birth defects, nor should there be any risks to future pregnancies.3 There is no known site of longer term carriage (such as in semen) in women.

Advise all travellers on how to avoid mosquito bites

If travel to an affected area is unavoidable, healthcare providers should fully inform the individual on avoidance of mosquito bites. Aedes mosquitoes bite from dawn through to dusk (only rarely at night), and 24 hour preventive measures should be encouraged. DEET based insect repellents should be used and applied frequently, and other measures should be pursued (see box 4).

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