Gina McAllister, Clinical Scientist Zika Virus Update Gina McAllister, Clinical Scientist

Aspects Background: virology Epidemiology Research Public Health recommendations and clinical algorithms. Future: vaccines Where to get more information

Moritz U. G. Kraemer and others The global distribution of the arbovirus vectors Aedes aegypti and Ae. albopictus (eLife, 30 June 2015)

Zika cases diagnosed in the UK As of 28 December 2016 there were 281 travel-associated cases diagnosed since 2015: 144 cases with virus detected [PCR positive]. 47 cases with antibody evidence indicating recent infection [seroconversion] and 90 cases that have antibody evidence highly indicative of recent infection (Zika-specific IgM) [probable cases]. Of the total 281 travel-associated cases reported, seven have been diagnosed in pregnant women. In addition, one case of likely sexual transmission of Zika virus infection has been reported in the UK.

Zika Virus Symptoms Asymptomatic infections are common, only one in four people infected with ZIKV are believed to develop symptoms. The disease symptoms are usually mild and last for 2 to 7 days. Signs and symptoms suggestive of Zika virus infection may include a combination of the following: Maculo-papular rash (90%) itching or pruritus fever (65%) headache (45%) arthralgia or arthritis (65%) myalgia (48%) Nonpurulent conjunctivitis (55%) lower back pain retro-orbital pain (39%) oedema (19%) vomiting (10%).

PH implications 8

Imaging On Examination Cerebral and cerebellar atrophy Microcephaly Cerebral calcifications Craniofacial disproportion Ventriculomegaly Redundant scalp skin Cortical and white matter abnormalities (eg agyria, pachygyria, lissencephaly) Closed anterior fontanelle Internal hydrocephalus Exuberant external occipital protuberance Periventricular cysts Intrauterine growth restriction Choroid plexus cyst Contractures Blake’s cyst Talipes Mega cisterna magna Umbilical hernia Vermian dys/agenesis Hypertonia or spasticity Callosal abnormalities Hyperreflexia Brain stem/spinal cord degeneration Irritability, convulsions, tremors Ocular abnormalities (intraocular calcifications, cataracts, microphthalmia, macular alterations, optic nerve abnormalities Hearing and visual abnormalities

Emerging evidence and big unknowns If there’s a safe time during your pregnancy to travel to an area with Zika? How risky is infection in pregnancy? Out of the 875 pregnancies with possible evidence of Zika in the USA there were 36 (4.1%) infants born with birth defects and 5 (0.57%) miscarriages/still births. NEJM paper: 29% of 42 pregnant women with confirmed Zika infection during pregnancy had adverse outcomes. How likely it is that Zika infection will affect your pregnancy?  Is there a risky period in pregnancy? Lancet paper: Estimated risk of microcephaly in fetuses and babies born to mothers infected with the Zika virus in the first trimester to be 1 in 100, or 1%. Modelling suggests microcephaly risk due to ZIKV infection during the first trimester might be higher: 0.88 to 13.2%. If your baby will have birth defects if you are infected while pregnant. Cauchemez et al. Lancet March 2016 Brasil et al. N Eng J Med 2016 Johansson et al N Eng J Med 2016 10

Clinical Scenario 28 year old female, returned from Jamaica on Saturday Had been on Honeymoon O/E Evidence of mosquito bites While away had episode of headache, myalgia and conjunctivitis. Partner asymptomatic   “Should I be tested for Zika?” “How long till we can start trying for a baby?” 11

Women who are planning pregnancy After a woman leaves an area with active Zika virus transmission, it is recommended that she should avoid becoming pregnant for 8 weeks Should also consider partner’s status.. 12

Preventing sexual transmission If a female partner is at risk of getting pregnant, or is planning pregnancy, effective contraception is advised to prevent pregnancy AND condom use is advised during vaginal, anal and oral sex for a male traveller to reduce the risk of transmission during travel and for: six months after his return from an area with active Zika virus transmission or the remaining duration of pregnancy if he is the partner of a pregnant woman, regardless of a history of symptoms suggestive of Zika virus infection. 13

Advised to postpone non-essential travel Women who are already pregnant Advised to postpone non-essential travel If travel is essential, educate about risk as far as possible. Strict bite avoidance day and night is essential. Advise use of barrier methods to prevent potential sexual transmission of ZIKV from a male partner during travel and throughout the pregnancy. On return, early obstetric review is recommended even if well. 14

Investigation of patients with current or previous symptoms Clinicians should consider Zika virus infection for: any patient who has, or has had, a rash illness or fever, or other symptoms suggestive of Zika virus infection, that began whilst in any country with active Zika virus transmission, or within 2 weeks of leaving that country any patient presenting with typical Zika-like symptoms apparently due to sexual transmission in the UK; that is, there is no history of travel or the symptoms began more than 2 weeks after travel to a Zika-affected country, and their sexual partner (especially if male) had travelled within the last 8 weeks from a country with active Zika virus transmission. If typical Zika-like symptoms develop between 8 weeks and 6 months of a male sexual partner having left a Zika affected country, the case should be discussed with RIPL

Returned traveller (or UK visitor) Current symptoms consistent with Zika infection Previous symptoms consistent with Zika infection (none now Never had symptoms suggestive of Zika infection Pregnant woman or male partner of pregnant woman Serum, EDTA plasma and urine. Serum. Also urine if within 21 days since symptom onset. No testing. Advise on prevention of sexual transmission Other returned traveller/UK visitor not in above group Serum and EDTA plasma only. Serum only. No testing. Advise on prevention of pregnancy and sexual transmission

Investigation of asymptomatic returned travellers The Zika virus testing service is currently not available for individuals who have had no symptoms suggestive of Zika infection. This includes: asymptomatic pregnant women who have travelled from Zika-affected countries asymptomatic returned male travellers whose partners are currently pregnant asymptomatic returned male and female travellers who are trying to conceive These individuals should be advised to follow PHE guidance on prevention of pregnancy and avoidance of sexual transmission as appropriate.

Date of Travel Date Returned Onset date Gestation Countries/areas visited Vaccination History

Women who are already pregnant 19

The Future

Vaccines US National Institute for Allergy and Infectious Disease has already created vaccine platforms for other flaviviruses that can be used as a starting point for a Zika vaccine. Several vaccine approaches: A DNA-based vaccine that uses a strategy similar to a flavivirus vaccine for West Nile Virus (already tested in phase 1 trials) A live-attenuated Zika vaccine building on a similar vaccine approach for dengue virus.

Sources of information Health Protection Scotland http://www.hps.scot.nhs.uk/internationalissues/zika.aspx ECDC for affected countries Any queries call: Virology Health Protection Team Obstetricians 22