Key learning points:
– The Zika virus is a mosquito-borne virus that has recently caused new outbreaks throughout the Americas, the Pacific and Caribbean Islands
– Most infections are asymptomatic or cause a mild illness but the virus can cause serious congenital abnormalities during pregnancy
– The diagnostic capabilities are currently limited, although specific antibody tests are being evaluated
The Zika virus is a mosquito-borne pathogen from the flavivirus family, which includes dengue, yellow fever, Japanese encephalitis and West Nile virus.
Until outbreaks occurred in French Polynesia (2013-14) and Brazil (2015), the disease was considered to be benign and of little concern. This changed when warnings emerged about the possible link between the Zika virus, microcephaly and other serious congenital abnormalities in pregnant women. The World Health Organization (WHO) declared Zika virus a public health emergency of international concern in February 2016.
Where did the infection originate and where is it currently active?
The virus was first identified in Africa more than 50 years ago, but few human cases were reported until large outbreaks occurred in the Pacific islands – in Yap in 2007 and French Polynesia in 2013-14. More recently, the virus spread to Asia and the Americas, with the largest outbreak, an estimated 161,000 cases, reported from Brazil.1 The main areas currently affected are the Caribbean, Central and South America, and some Pacific islands but there is now widespread transmission in Thailand and Vietnam, and spread is expected throughout other parts of Asia. The African strain of the virus has been implicated in a recent outbreak in Cape Verde.
Information on the current status of Zika virus transmission is provided by the European Centre of Disease Prevention and Control (ECDC) (see Resources).
Vector and mode of transmission
Like dengue fever, the Zika virus is spread to humans through the saliva of infected Aedes mosquitoes (mainly Aedes Stegomyia, aegypti and possibly albopictus) during a blood meal. Aedes mosquitoes are found worldwide, in tropical and in temperate climates, including the USA and Europe. They breed both in and outdoors and their eggs can be found in almost any container that holds water including old snail shells, buckets and tyres. They are predominantly daytime feeders. The virus remains in the insect life-long, and it is likely that nonhuman primates and other small mammals also act as a host.
One of the biggest concerns about the Zika virus is the difficulty in eradicating the mosquito that transmits it. The use of pesticides to clear indoor areas of mosquitoes and surrounding breeding sites is problematic as they need to be safe, effective and environmentally friendly. This is why efforts to control the Aedes vector have proved unsuccessful, as evidenced by the huge increase in dengue outbreaks worldwide, making dengue the most important mosquito-borne viral disease worldwide.
The Zika virus has also been isolated from semen. This mode of spread is important as sexual transmission is a risk to women who are pregnant or planning to become pregnant if their partner is harbouring the virus. All pregnant women should use effective contraception if they or their partner have been in a Zika region. It is not yet known how long the virus can be detected in semen, but men should be encouraged to use condoms for six months following symptoms consistent with the Zika virus.
Advice for individuals planning travel to Zika-infected areas
As there is currently no vaccine available to prevent the infection, travellers need to rely on insect bite avoidance measures. Aedes mosquitoes are predominantly daytime feeders so travellers should protect themselves from bites throughout the day. Protection includes wearing clothing that covers their arms and legs, and applying insect repellents regularly. Repellents containing N.N-diethyl-meta-toluamide (DEET) are effective at repelling Aedes mosquitoes2 and are safe to apply in pregnancy and to infants.3 DEET concentrations of between 30-50% are usually recommended.
Most travellers do not need to alter their travel plans as the majority of infections, around 80%,4 will be asymptomatic. If symptoms do develop, the illness is usually mild and self-limiting. There is, however, a small risk of serious complications including severe congenital abnormalities in pregnancy, therefore pre-travel advice is extremely important for those who are pregnant or planning pregnancy.
The current advice from national and international travel health advisory bodies, the WHO, the United States Centers for Disease Control and Prevention (CDC) and the UK National Travel Health Network and Centre (NaTHNaC) is for pregnant travellers to avoid visiting areas where they could be exposed to the Zika virus. Pregnancy should be avoided prior to, during, and for 8 weeks after travel to a risk area. Because of the rare risk of sexual transmission, if a male has travelled to a risk area, effective contraception should be used for:
– 8 weeks after return if he has not had symptoms.
– Six months after recovery if he has been symptomatic.
– The entire period of pregnancy.
– Women who have travelled during pregnancy should seek advice from their GP or midwife on their return.
NaTHNaC has an algorithm for reducing the risk of Zika virus transmission in pregnancy (see Resources). Healthcare professionals can contact NaTHNaC for up-to-date information for patients who are travelling. The Hospital for Tropical Diseases in London also runs a travel health advice service.
Assessment of travellers returning from areas of Zika virus transmission
Annually around 2.5 million UK travellers visit areas where Zika virus transmission is ongoing, and about a quarter of those will be women of childbearing age. Therefore we can assume that a substantial number of returning travellers will present to their GP surgery, particularly if pregnant or planning to become pregnant. The Hospital for Tropical Diseases has seen a large influx of people seeking both pre and post travel advice since awareness was raised about the risks of the Zika virus.
Of those who become symptomatic, most will experience a mild illness lasting three to five days. The main symptoms are fever, rash, pruritus, a maculo-papular rash, muscle and joint pain, headache, conjunctivitis, lower back pain and retro-orbital pain. The incubation period is short (three to seven days). It is unclear, but likely, that Zika infection confers long-term immunity. It has not been determined whether previous infection by dengue, chikungunya or yellow fever vaccination affects Zika infection or severity.
A travel history and details of symptoms will determine whether tests for Zika infection should be taken. The symptoms are not particularly helpful, though, as they are typical of a number of other viral infections, for example dengue and chikungunya, which are likely to be contracted in the same locations as the Zika virus.
Details of laboratory testing for Zika infection are discussed below. It is important to exclude other potentially fatal infections such as malaria, as a matter of urgency, if the traveller has visited endemic areas such as the Amazon area of Brazil.
Who should be tested?
Tests for the Zika virus should be carried out on all travellers who have returned from areas where active Zika transmission is occurring (see ECDC link in resources) if they have symptoms suggestive of infection.
Where testing is appropriate, this should ideally be carried out within two weeks of returning from a risk area.
How to test for Zika virus infection
Guidance on the laboratory samples to be taken to diagnose Zika infection has been issued by Public Health England (PHE) and full details can be found on its website (see Resources). Experience with diagnostic tests for Zika infection is, however, very limited and the guidance will change as different tests are evaluated and made available. Samples should be sent to PHE’s Rare and Imported Pathogens Laboratory (RIPL). Samples of both blood and urine may be needed.
The test of choice is a reverse transcriptase-polymerase chain reaction (RT-PCR) test to detect viral RNA in blood and other body fluids. But it is only detectable in blood for a few days so the test should be carried out within the first two weeks of the onset of symptoms. Urine PCR is positive for longer – up to 30 days.
If symptomatic travellers are seen beyond this period, a more useful test is one that detects Zika virus antibodies – these take around a week to develop after symptoms occur. Antibody tests (IgM and IgG and neutralising antibodies) are currently being evaluated for use and it is likely they will be available soon. A problem with antibody tests is that the earlier tests also reacted with related flaviviruses (eg, dengue and yellow fever), making them difficult to interpret.
The Hospital for Tropical Diseases can provide advice to healthcare professionals on the management of suspected Zika virus infections. Recently returned symptomatic travellers can attend the walk-in clinic at the Hospital for Tropical Diseases without a referral from their GP.
Management of symptomatic returned travellers
There is no specific treatment for Zika virus. Supportive care with analgesia and bed rest is usually all that is needed for the short duration of symptoms.
There are, however, some serious complications associated with Zika infection, one of which is Guillain-Barré syndrome (GBS). GBS is a condition where an infection can trigger the immune system to attack the peripheral nervous system. Campylobacter and cytomegalovirus infections are some of the more common infections linked to GBS. Prolonged support may be needed and a proportion of patients will be left with a disability.
Management of pregnant travellers returned from Zika-infected area
One of the most disturbing manifestations of Zika infection is the damage to fetal brain development when infection occurs during any stage of pregnancy. Zika virus RNA have been detected in the placenta, amniotic fluid, fetal blood, brain tissue and cerebrospinal fluid following miscarriage, stillbirths or after termination of pregnancy.
Estimates from French Polynesia indicate an approximate 1% risk of microcephaly associated with Zika virus infection in the first trimester of pregnancy.5 A wide range of other congenital cerebral abnormalities have also been reported, including brain calcifications, impaired eyesight and hearing – now referred to as ‘congenital Zika syndrome’.
Pregnant women who present with symptoms consistent with Zika virus infection during or within two weeks of travel should be tested and if positive referred to a fetal medicine service. Those whose symptoms have resolved or who have a negative test should be given a baseline fetal ultrasound. These may be repeated at four weekly intervals and, if abnormal, a referral should be made to a specialist fetal medicine service. This is a very stressful time for a pregnant woman and their partner. Nurses and GPs may find the Royal College of Obstetricians and Gynaecologists website a useful resource when providing support (see Resources).
The ECDC has produced a map of Zika transmission areas in the last nine months. This will help to decide if a woman has been in an affected area during pregnancy (see Resources).
The advice may change with more experience of the infection in pregnancy. In the interim, PHE has issued an algorithm for assessing women who have travelled to areas with active Zika virus transmission while pregnant (see Resources).
No evidence exists that pregnant women have increased susceptibility to Zika virus disease, or more severe illness.
The Zika virus has spread to many countries over a timescale of months and continues to spread north towards the North American continent, which has led to concerns about the global threat of the disease. The very disabling neurological and teratogenic effects during pregnancy have resulted in widespread anxiety and disruption to travel plans of pregnant travellers.
Diagnosis is problematic as the most reliable test is the RT-PCR, which has a limited window of effectiveness. Antibody tests are being evaluated to overcome the problems of cross-reactivity to other flavivirus infections.
The vector transmission of the virus will be difficult to control as the Aedes mosquito is widespread in tropical and subtropical countries and in parts of southern Europe.
While the majority of infected individuals will be asymptomatic or have shortlived symptoms, very distressing fetal and neonatal abnormalities have been associated with Zika infection as have increasing numbers of GBS cases. Because of the risk to pregnant women the experts advise that travel to risk areas should be postponed.
Pregnant women who present with symptoms compatible with Zika infection during or within two weeks of travel to a risk area should be tested. If positive they should be referred to a fetal medicine service. Those who are asymptomatic or have a negative test should be offered baseline fetal ultrasound and be assessed at regular intervals throughout the pregnancy.
Because of the slight risk of sexual transmission to women of childbearing age, unprotected sex should be avoided for six months if a partner has had symptoms suggestive of Zika infection.
ECDPC. Zika virus transmission in the last 9 months.
ecdc.europa.eu/en/healthtopics/zika_virus_infection/zika-outbreak/Pages/Zika-countries-with-transmission.aspx#currentactive (accessed 10 May 2016).
National Travel Health Network and Centre. Algorithm. Travel to area with active ZIKV transmission.
travelhealthpro.org.uk/wp-content/uploads/2016/03/Travel-to-area-with-active-ZIKV-transmission.pdf (accessed 10 May 2016).
Public Health England. Zika virus: sample testing advice.
gov.uk/guidance/zika-virus-sample-testing-advice (accessed 12 May 2016).
ECDPC. Zika virus transmission in the last month, map.
ecdc.europa.eu/en/healthtopics/zika_virus_infection/zika-outbreak/Pages/Zika-transmission-past-9-months.aspx (accessed 9 June 2016).
Public Health England. Interim algorithm for assessing pregnant women with a history of travel during pregnancy to areas with active Zika virus (ZIKV) transmission.
gov.uk/government/uploads/system/uploads/attachment_data/file/519205/Interim_Zika_testing_algorithm_for_assessing_pregnant_women_with_a_history_of_travel_v5.pdf (accessed 10 May 2016).
Royal College of obstetricians and Gynaecologists. Q&As related to Zika virus and pregnancy.
rcog.org.uk/en/news/qas-related-to-zika-virus-and-pregnancy/#q18 (accessed 10 May 2016).
Contacts for further advice
Hospital for Tropical Diseases
The Hospital for Tropical Diseases has a walk in clinic where ill returned travellers can attend without a referral or appointment.
Address: The Hospital for Tropical Diseases (HTD), Mortimer Market, Capper Street, Tottenham Court Road, London, WC1E 6JB
Telephone: 020 345 67891, Fax: 020 3447 9675
For clinical enquiries healthcare professionals can contact the Hospital for Tropical Disease registrar via University College London Hospitals’ switchboard (0203 456 7890).
National Travel Health Network and Centre
Travel health advice for healthcare professionals is available from the National Travel Health Network and Centre (NaTHNaC) on Telephone: +44 (0)845 602 6712 (local call rate).
1. WHO. Cumulative Zika suspected and confirmed cases reported by countries and territories in the Americas, 2015-2016. ais.paho.org/phip/viz/ed_zika_cases.asp (accessed 9 July 2016).
2. Lupti E, Hatz C, Schlagenhauf P. The efficacy of repellents against Aedes, Anopheles, Culex and Ixodes spp – A literature review. Travel Medicine and Infectious Disease 2013;11:374-411.
3. Stanczyk NM, Behrens RH, Chen-Hussey V et al. Mosquito repellents for travellers. British Medical Journal 2015;350:99.
4. Chang C, Ortiz K, Ansari A, Gershwin ME. The Zika outbreak of the 21st century. Journal of Autoimmunity 2016;68:1-13.
5. Cauchemez S, Bersnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D, Salje H, Van Kerkhove MD, Abadie V, Garel C, Fontanet A, Mallet HP. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet 2016;387:2125-2132.