Zika virus is a mosquito-borne infection. It was originally described in Africa in 1947 but is currently spreading rapidly through the Americas. An outbreak in Brazil in 2015 was followed by a twenty-fold increase in the number of babies born with microcephaly. Evidence is still being collected on whether this is a result of Zika virus infection. Subsequently the authorities in Brazil declared a public health emergency and the World Health Organisation (WHO) declared Zika virus to be a public health emergency of international concern in 2016.
Zika is an arbovirus spread through the bite of the Aedes mosquito, particularly Aedes aegypti. This is the same species of mosquito which transmits chikungunya fever, yellow fever and dengue. Aedes mosquitoes tend to bite during the daytime, unlike malaria-transmitting mosquitoes which are more likely to bite between dusk and dawn.
Other methods of transmission reported include:
- Sexual transmission. This has been described in two cases and the virus has been found in semen post-infection in two other cases[1, 2].
- Vertical transmission (mother to fetus). Evidence is accumulating linking Zika virus and babies born with microcephaly. Zika virus has been isolated from amniotic fluid of pregnant women who had babies with microcephaly in Brazil. Zika virus has also been found in brain tissue of two neonates with microcephaly who died shortly after birth, and in placental tissue following two early miscarriages. The four mothers reported having had symptoms compatible with Zika virus infection in early pregnancy.
- Blood donation.
Zika virus was first described in Uganda in 1947 in rhesus monkeys in a primate and mosquito surveillance programme. It was confined to a small area of Africa and Asia until outbreaks in Yap Island in 2007 and French Polynesia in 2013. It was first confirmed in Brazil in May 2015 and, by February 2016, locally acquired cases have been identified in over 30 countries in South America, Central America, the Caribbean and the Pacific. The regularly updated list of affected countries is available on the Public Health England (PHE) website. If the virus adapts, it may be transmissible by the Aedes albopictus mosquito, which would then allow it to spread widely into North America.
Although cases have been confirmed in the UK, these have been acquired by individuals travelling abroad to affected countries. The climate in the UK is not favourable for survival of the Aedes mosquito.
It is difficult to obtain accurate figures of people who have been affected by the outbreak, as the majority probably do not present because the illness is so mild. It has been estimated that there have been 1.5 million cases in Brazil since the beginning of the outbreak and February 2016, and 25,000 in Columbia.
Generally, Zika virus results in a mild clinical infection; most people who are affected have no symptoms. Where there are symptoms, onset is usually 3-12 days after being bitten by the mosquito. There may be a mild febrile illness for 2-7 days and symptoms may include:
- Arthralgia and myalgia.
- Rash (widespread and may be itchy).
- Retro-orbital pain.
- Peripheral oedema.
- Gastrointestinal upset.
Consider Zika virus in individuals returning from affected countries. The differential diagnosis includes chikungunya fever and dengue, both of which are found in the same geographical areas, and symptoms may be similar. Laboratory testing is required to distinguish between these illnesses.
Other diagnoses to consider include:
PHE advises that tests are indicated only for a person who has travelled to or arrived from an area with active Zika virus transmission, and within two weeks of return to the UK, who presents with active symptoms at the time of assessment.
For those fulfilling these criteria, blood samples are taken and sent to PHE's Rare and Imported Pathogens Laboratory (RIPL). In pregnant women, a urine sample should also be sent (without preservative). Liaise with the local laboratory to arrange this, and complete an RIPL form along with the local laboratory request form. Virus RNA is detected in positive samples by polymerase chain reaction (PCR).
Management is essentially supportive. There is no antiviral medication for Zika at this time. It is usually a mild illness with little need for medical intervention.
Zika virus in pregnancy
An interim algorithm has been produced by the Royal College of Obstetricians and Gynaecologists (RCOG), Royal College of Midwives (RCM), Public Health England (PHE and Health Protection Scotland (HPS)) for health professionals assessing pregnant women with a history of travel during pregnancy. This is available on the PHE website and is expected to be updated as further information arises. It advises testing of symptomatic pregnant women who have travelled to affected areas, and serial ultrasound scans even of women who have had no symptoms but have travelled to affected areas. See the latest algorithm for full details.
Dr Hayley Willacy notes that the United States Centers for Disease Control and Prevention (CDC) have just released interim guidance for healthcare providers caring for pregnant women with possible Zika virus exposure. IgM test results do not always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counselling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy.
The possible complications and associations of Zika virus infection are the reason for international news headlines, research and concern. This follows descriptions of increases in numbers of cases of certain congenital abnormalities and also neurological and autoimmune syndromes in areas where Zika virus is currently prevalent, particularly in Brazil. The following possible complications have been identified; however, as yet there is no evidence of a definite causal relationship.
As detailed above, a twenty-fold increase in births of babies with microcephaly in 2015 was reported in Brazil. There is evidence of an association with Zika; however, this has not been the case in other countries with outbreaks of Zika, such as Columbia. Moreover, on further investigation, many cases were found not to have microcephaly. Further investigation is urgently underway. However, there was enough evidence of a possible link for the WHO to declare a public health emergency and for a flurry of guidelines to be produced regarding advice for pregnant women planning to travel to, or return from, affected countries and for the health professionals involved in their care. In the UK this includes an interim clinical guideline from the RCOG/RCM/PHE/PHS. The National Travel Health Network and Centre (NaTHNaC) currently advises that pregnant women should consider avoiding travel to countries where Zika is prevalent.
From information available to date, it appears infection with Zika in the early stages of pregnancy confers the greatest risk of fetal damage, if maternal infection with Zika is responsible.
Guillain-Barré syndrome (GBS)
During the epidemic in French Polynesia, there was a significant increase in documented cases of GBS and other neurological conditions that were thought to have an association with Zika virus infection. Brazil also reported an increase in GBS in 2015, and other countries including El Salvador, Colombia, Suriname and Venezuela have also reported a similar change.
In February 2016, a study of 42 cases of GBS during the time of the Zika virus outbreak in French Polynesia reported evidence of Zika virus infection in every single one, as compared to 58% of a control group, thought to be early evidence confirming a causative link.
Other neurological complications
The Pan American Health Organization/WHO issued an alert to its member states in December 2015, advising intensification of surveillance of neurological syndromes and birth defects, notification of confirmed cases of Zika virus and preventative measures.
A number of preventative strategies are advised, both on national and personal levels.
Nationally, governments are advised to take measures to control the mosquito population. This includes removal of mosquito breeding sites (such as areas which collect standing water) and spraying of insecticides. Genetic weapons are being tried, such as releasing genetically modified male mosquitoes, in the affected areas, to breed with the local female populations. These mosquitoes carry a gene which makes subsequent eggs non-viable. Another strategy involves releasing bacteria into the environment, which can prevent mosquitoes reproducing.
Several research centres are working on vaccine development but this is expected to take at least 18 months before large-scale trials begin. Prophylactic antiviral medication is also being studied.
Enhanced surveillance of cases and complications is advised, with international communication and collaboration.
Changes to protocols in blood donation services have been made. In the UK, people who have travelled to areas where Zika virus is prevalent are deferred for one month before giving blood. This is already the case in those travelling from high-risk tropical areas and so is unlikely to have significant impact on the service.
On a personal level, residents and travellers are advised about the following strategies:
- Use of mosquito netting, window screens and clothes (preferably light-coloured) which cover as much of the body as possible.
- Use of a good insect repellent containing N,N-diethylmetatoluamide (DEET) on exposed areas of skin.
- Avoidance of travel to affected areas by women who are pregnant or planning to become pregnant.
- Avoidance of pregnancy for 28 days by women returning from endemic areas.
- Men returning from affected areas are advised to avoid unprotected sex with female partners of childbearing potential for 28 days, and for six months if they have probable or confirmed infection
Further reading and references
Free Zika Virus resources; British Medical Journal (BMJ)
Zika Virus Infection; European Centre for Disease Prevention and Control (ECDC) (including epidemiological updates)
Zika Virus Infection, Guidance for Primary Care; Public Health England (PHE), the British Medical Association (BMA) and the Royal College of General Practitioners (RCGP)
Zika virus; World Health Organization, September 2016
Basarab M, Bowman C, Aarons EJ, et al; Zika virus. BMJ. 2016 Feb 26352:i1049. doi: 10.1136/bmj.i1049.
Calvet G, Aguiar RS, Melo AS, et al; Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis. 2016 Feb 17. pii: S1473-3099(16)00095-5. doi: 10.1016/S1473-3099(16)00095-5.
Martines RB, Bhatnagar J, Keating MK, et al; Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses - Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016 Feb 1965(6):159-60. doi: 10.15585/mmwr.mm6506e1.
Fauci AS, Morens DM; Zika Virus in the Americas--Yet Another Arbovirus Threat. N Engl J Med. 2016 Feb 18374(7):601-4. doi: 10.1056/NEJMp1600297. Epub 2016 Jan 13.
Zika virus; Public Health England
Zika virus: interim algorithm for assessing pregnant women with a history of travel; Public Health England
Epidemiological Update: Neurological syndrome, congenital anomalies, and Zika virus infection, January 17, 2016; Pan American Health Organization/World Health Organization
Interim clinical guidance on zika virus infection and pregnancy; Royal College of Obstetricians and Gynaecologists, January 2016
Zika virus – update and advice for travellers including pregnant women; National Travel Health Network and Centre (NaTHNaC)
Fontanet A et al; Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study, The Lancet, 29 February 2016
Maurice J; WHO reveals its shopping list for weapons against Zika. Lancet. 2016 Feb 20387(10020):733.