On 1 February 2016, the Director General of the World Health Organization (WHO) declared the recent outbreak of cases of fetal microcephaly linked to Zika in South America an international public health emergency (WHO, 2016a). As it is likely that some practising midwives in the UK will encounter women who are pregnant or planning to conceive and may have been exposed to Zika, it is important for midwives to be prepared for properly assessing and informing women with the infection. This article offers some insight into Zika and addresses the known effects of Zika during pregnancy, clinical management of women who are pregnant or planning pregnancy, and the implications of Zika for practising midwives in the UK.
What is Zika?
Zika virus disease is a mosquito-borne infection caused by Zika virus (ZIKV), a member of the Flavivirus genus. ZIKV was first observed in a monkey in the Zika forest in Uganda in 1947, and it was found a few years later in humans, animals and mosquitoes throughout Africa and Asia. In the past 9 years, large outbreaks have been reported in Micronesia, French Polynesia and other parts of the Pacific, typically accompanied by mild illness (Centers for Disease Control and Prevention (CDC), 2016a). In May 2015, the first case of local ZIKV transmission was reported in Brazil. Since then, ZIKV has spread rapidly across 40 countries, particularly affecting South America, Central America and the Caribbean (Pan American Health Organization (PAHO) and WHO, 2016). By October 2015, Brazil reported an association between ZIKV infection with both fetal microcephaly—small head for gestational age—and Guillain-Barré syndrome. Pacific Islands and Cape Verde have also reported active ZIKV transmission, and more recently, small outbreaks have also been reported in Southeast Asia and Florida, USA (CDC, 2016a; European Centre for Disease Prevention and Control, 2016) (Figure 1).
It has been recently suggested that the current Latin American Zika epidemic is likely to abate within 3 years as an increasing proportion of the population gain immunity (Ferguson et al, 2016). However, the wide global distribution of the mosquitoes able to transmit the virus means that subsequent epidemics are likely to occur in other parts of the world.
Transmission
Almost all reported cases of ZIKV in humans are acquired through a bite from an infected female Aedes species mosquito. After a person is bitten by an infected mosquito, the first symptoms usually appear in 3–12 days (CDC, 2016a). Sexual transmission has also been reported. Most cases have been male-to-female, but female-to-male and male-to-male transmission has occurred (Davidson et al, 2016). A few case studies have suggested that sexual transmission may occur shortly before, during and after symptomatic infection, and transmission may occur even from men who have had subclinical infection (Foy et al, 2011; Fréour et al, 2016; Hills et al, 2016; WHO, 2016b). Although the virus has been shown to remain in semen for 3 months following recovery from a typical Zika illness, its infectiveness remains uncertain (Mansuy et al, 2016). The risk of sexual transmission from infected asymptomatic men is currently unknown, as is whether infected pregnant women can transmit ZIKV to their sexual partners. ZIKV can be transmitted from a pregnant woman to her fetus via the placenta during pregnancy or birth, although the risk of perinatal transmission is still unknown (Besnard et al, 2014; Calvet et al, 2016; Martines et al, 2016; Mlakar et al, 2016). ZIKV has also been found in breast milk, but there is currently no evidence that the virus can be transmitted to infants via breastfeeding, so the standard advice to women regarding breastfeeding remains unchanged (Dupont-Rouzeyrol et al, 2016).
In addition, the virus has been detected in asymptomatic blood donors (CDC, 2016a).
Symptoms
The majority of people infected with ZIKV have no symptoms. In some cases, ZIKV tends to cause a mild illness with symptoms such as rash, fever, joint pains and conjunctivitis lasting between 2 and 7 days (CDC, 2016a) (Table 1). It is not yet known whether Zika symptoms are more severe in pregnant compared to non-pregnant women. The symptoms of ZIKV infection can be similar to those of dengue, yellow fever and chikungunya, which are other Aedes species mosquito-borne diseases that occur in the same geographical areas. Laboratory testing is therefore required for differential diagnosis. Death and serious complications from ZIKV infection are rare, although researchers have confirmed that the virus can cause fetal microcephaly and Guillain-Barré syndrome, a rare and potentially fatal autoimmune disorder that affects the nervous system, in adults (WHO, 2016c).
| Most common symptoms | Other symptoms |
|---|---|
| Fever |
Headaches |
Diagnosis
Diagnosis of ZIKV is made based on symptoms, travel or sexual exposure history and laboratory testing. Laboratory testing detects virus RNA in urine and blood samples by performing a reverse transcriptase-polymerase chain reaction (RT-PCR). However, ZIKV RNA is detectable in blood for only 5–7 days, and in urine for only 3 weeks, after symptom onset (CDC, 2016a; Public Health England (PHE), 2016b). Therefore, a negative PCR result may not ‘rule out’ Zika infection at any stage, including the first week of infection. Recently, serological tests have been developed to detect ZIKV-specific antibodies (CDC, 2016a; PHE, 2016b), which would be a useful ‘rule-out’ test of recent infection, but cross-reactivity with other viruses (e.g. dengue or yellow fever) or previous vaccinations (e.g. for yellow fever) remains a potential concern. Studies are underway to better understand the performance of current diagnostic and serological tests, the best method for interpreting the results, and the persistence of ZIKV (Table 2).
| Timeline of infection | Diagnostic test available |
|---|---|
| Within a few days (in blood) and 3 weeks (in urine) after symptoms begin | Polymerase chain reaction (PCR) for detection of Zika virus RNA [mainstay of diagnostic testing at UK] |
| From day 4 post onset of symptoms and continuing for 12 weeks |
|
| Within 7 days following onset of symptoms | Trioplex Real-time PCR (polymerase chain reaction) Assay for detection of Zika virus, dengue virus, and chikungunya virus RNA* |
Treatment and vaccines
There is currently no vaccine to prevent ZIKV transmission or specific drugs to treat ZIKV infection. As the infection is usually mild and short-lived, supportive nursing care and symptom relief are the standard treatments. The key to preventing ZIKV infection is protection against Aedes species mosquitos, which feed aggressively during the day both indoors and outdoors. Such protection includes covering as much exposed skin as possible, wearing long sleeves and trousers, choosing loose and light-coloured clothes, sleeping under mosquito nets and regularly using insect repellents with DEET concentrations of up to 50%, which are commonly available and are safe for pregnant and breastfeeding women (WHO, 2016d).
‘ZIKV's interactions with pregnancy remain poorly understood. There is currently no evidence to suggest that the disease is more severe in pregnant women than in non-pregnant individuals or that pregnant women have a greater risk of contracting Zika virus’
Pregnancy and Zika
The WHO has reported that there is a strong scientific consensus that ZIKV can cause fetal microcephaly and other brain abnormalities, such as atrophy, cerebral cysts or ventriculomegaly (Brasil et al, 2016; Mlakar et al, 2016; Oliveira Melo et al, 2016), which are now collectively termed ‘congenital Zika syndrome’ (CZS) (WHO, 2016c). Brazil, the country that has been most affected by the virus, has reported more than 6500 suspected cases and more than 1650 confirmed cases of CZS to date (PAHO and WHO, 2016). Scientists are still collecting more data to better understand how the virus affects mothers and children. However, it is clear that microcephaly can have wide and varying impacts. Infants born with possible CZS may face a greater risk of significant health problems and disability throughout their lives (i.e. impaired growth, learning disabilities, hearing loss and vision problems) (CDC, 2016b), which leads to significantly increased health care costs and negative effects on the economy and society as a whole.
ZIKV's interactions with pregnancy remain poorly understood. There is currently no evidence to suggest that the disease is more severe in pregnant women than in non-pregnant individuals or that pregnant women have a greater risk of contracting ZIKV (Royal College of Obstetricians and Gynaecologists (RCOG) et al, 2016). It is also unknown whether pregnant women are more susceptible to Guillain-Barré syndrome. Brasil et al (2016) found that 12 out of 42 (29%) pregnant women infected with ZIKV had fetuses or infants with birth defects, including one infant born with severe microcephaly; by contrast, 16 pregnant women who tested negative for ZIKV had normal ultrasound scans. The latest evidence suggests that a fetus infected in early gestation is more likely to have severe microcephaly and adverse outcomes compared to those infected later in the pregnancy (Cauchemez et al, 2016; Johansson et al, 2016). Cauchemez et al (2016) estimated that around 1% of pregnant women infected by ZIKV during the first trimester in the French Polynesia outbreak in 2014 had infants with microcephaly. In one recent study in Brazil, of 35 infants with microcephaly, 21 were born to women who reported a rash in the first trimester and five were born to women who reported a rash in the second trimester (Schuler-Faccini et al, 2016). However, a case report detected congenital abnormalities in infected unborn babies at 27 weeks' gestation (Brasil et al, 2016). The number of cases reported so far are small, so studies can not completely exclude causes other than Zika for the microcephaly cluster e.g rubella, cytomegalovirus (CMV) infection and herpes simplex (Butler, 2016).
Because knowledge about ZIKV and pregnancy is still very limited, midwives may find it challenging to manage the expectations of women who are pregnant or planning pregnancy (and their partners) who may have been exposed to the virus, even if they have had no symptoms associated with ZIKV infection. RCOG, the Royal College of Midwives (RCM), PHE and Health Protection Scotland have published joint guides and flowcharts for midwives, obstetricians and other health professionals, although these recommendations will likely be updated regularly to reflect new evidence (Table 3).
| Clinical guidelines for managing Zika virus exposure in pregnancy |
| Zika Virus Infection and Pregnancy: Information for Healthcare Professionals |
| Pre-travel telephone advice to health professionals |
| Zika virus (ZIKV): clinical and travel guidance |
| Clinical assessment of returning travellers with symptoms (including unwell pregnant women) |
| Hospital for Tropical Diseases |
| How to send samples for Zika virus testing |
| Rare and imported pathogens laboratory |
| General information |
| Royal College of Midwives |
Advice for women planning pregnancy
Currently, women should avoid becoming pregnant while travelling to a country with active ZIKV transmission, and for 8 weeks after returning home (PHE, 2016a). Nurses and midwives should discuss effective contraception methods and condom use with couples in which the male partner has been in an area with Zika. The aim is to prevent pregnancy and reduce the risk of sexual transmission during travel, for 8 weeks after returning for those with no symptoms, and for 6 months following the onset of symptoms of suspected or confirmed ZIKV infection.
Women planning pregnancy who develop symptoms associated with ZIKV infection on returning to the UK after travelling should avoid becoming pregnant for 8 weeks following recovery (Faculty of Sexual and Reproductive Healthcare, 2016; PHE, 2016a). Latest WHO recommendations on delaying pregnancy for at least 6 months after return is under discussion in UK at the moment (WHO, 2016f).
Clinical management of pregnant women exposed to ZIKV
Midwives are advised to ask all pregnant women and their partners about recent and planned travel at all antenatal visits. The WHO is currently advising all pregnant women to not visit areas with ongoing ZIKV transmission and to weigh the personal risks and benefits. If travel cannot be postponed, pregnant women should be counselled to strictly follow mosquito bite precautions during the trip, and either use condoms correctly and consistently or abstain from sex for the duration of the pregnancy.
Midwives should consider ZIKV infection when encountering pregnant women who have symptoms suggestive of ZIKV and have travelled to a ZIKV-affected country or have had contact with someone who recently travelled to a ZIKV-affected area within the previous 2 weeks. Support can be sought from specialist midwives, obstetricians and infectious disease specialists to test those women and their partners for virus RNA using real-time polymerase chain reaction (RT-PCR) and ZIKV antibodies testing.
‘Women whose fetuses have significant microcephaly or brain abnormalities who have laboratory-confirmed ZIKV infection are highly likely to have poor pregnancy outcomes’
If laboratory testing shows evidence of ZIKV infection, the woman should be offered a baseline fetal ultrasound and be referred to a fetal medicine service for further evaluation and follow-up. If the woman is seriously unwell and requires hospitalisation, she should be tested for other travel-related infections (i.e. malaria or dengue fever) and other causes of rash in pregnancy (i.e. rubella, chickenpox, acute HIV infection, syphilis, CMV) (PHE, 2016c).
Pregnant women who report no symptoms within 2 weeks after returning from a ZIKV-affected area do not require testing. However, as ZIKV infections are asymptomatic in most individuals, a baseline fetal ultrasound should be offered and repeated at 18–20 weeks' gestation and a repeat considered at 28–30 weeks in line with WHO (2016e) guidelines.
Male travellers who previously had symptoms associated with ZIKV and whose partners are currently pregnant may require testing for ZIKV. Midwives should discuss individual cases with health professionals from multiple disciplines.
ZIKV testing and referral to a fetal medicine unit is recommended for pregnant women whose fetuses have been diagnosed with fetal microcephaly or other brain abnormalities, and women who have been exposed to ZIKV infection through either sexual contact or travel to a ZIKV-affected country during pregnancy. Most infants with a head circumference more than two standard deviations below the mean for gestational age will be normal; microcephaly is usually diagnosed when an infant's head circumference is smaller than this, and other brain abnormalities (i.e. intracranial calcifications) have been detected on ultrasound or further fetal brain MRI.
Amniotic fluid can be tested using RT-PCR 6 weeks after exposure to ZIKV if the woman is ≥ 21 weeks into the pregnancy (Vouga et al, 2016). However, it is not known how sensitive this test is regarding CZS and how likely it is that an infected fetus will be affected. Amniocentesis also carries a small risk of miscarriage and preterm birth, so the procedure should only be performed after thorough counselling.
Women whose fetuses have significant microcephaly or brain abnormalities who have laboratory-confirmed ZIKV infection are highly likely to have poor pregnancy outcomes. Midwives should work together with a multidisciplinary team of obstetricians, infectious disease specialists, neonatologists and paediatricians, and thoroughly discuss with pregnant women the risk of spontaneous abortion or stillbirth, the possibility of terminating the pregnancy (regardless of gestation) and the management of neonates, including surveillance for congenital anomalies in later life that are associated with ZIKV infection.
Conclusion
The current epidemic in the Americas has confirmed that ZIKV infection during pregnancy can cause fetal microcephaly and other serious brain abnormalities, yet the wider effects of ZIKV and the magnitude of the risk of infection at different gestational ages remains uncertain.
In light of recent evidence, women who are pregnant or planning to become pregnant are advised to take precautions to avoid ZIKV infection, such as postponing travel to Zika-affected countries, taking scrupulous measures to avoid mosquito bites and practising safe sex if travel is unavoidable for them or their male partners. Additionally, these women should inform their midwives, GPs or obstetricians about recent travels, even if they present no symptoms.
Midwives are advised to keep regularly updated on guidelines from PHE, the RCM and RCOG in order to accurately assess pregnant women who may have been exposed to ZIKV, using methods such as examining their travel history, testing and—if required—referral to a fetal medicine unit.