Zika virus: a new global threat for Dr Gina McAllister Clinical Scientist, Virology

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1 Zika virus: a new global threat for 2016 Dr Gina McAllister Clinical Scientist, Virology

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

6 European Distribution Aedes albopictus

7 Transmission Vector borne transmission by Aedes mosquitoes Other routes of transmission Trans-placental transmission. Potential risk of transmission via blood transfusion. Sexual transmission through semen. Viral RNA has been detected in sperm up to 62 days after the onset of symptoms. Atkinson et al. Emerg Infect Dis Feb 2016.

8 Zika Virus Disease 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. Common symptoms are maculo-papular rash (90%), fever (65%), arthritis or arthralgia (65%), nonpurulent conjunctivitis (55%), myalgia (48%), headache (45%), retro-orbital pain (39%), oedema (19%) and vomiting (10%).

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10 Zika Virus and Microcephaly 6906 cases of microcephaly and/or CNS malformation. 227 deaths. 21 out of 27 states in Brazil

11 Rasmussen et al., NEJM April 2016

12 Shepherd s Criteria 1. Proven exposure to the agent at one or more critical times during prenatal development. 2. Consistent findings by >/=2high-quality epidemiological studies. 3. Careful delineation of clinical cases; a specific defect or syndrome is very helpful. 4. Rare environmental exposure that is associated with a rare defect. 5. Teratogenicity in experimental animals. 6. Association should make biological sense.

13 Mlakar et al NEJM Feb 2016

14 Shepherd s Criteria 1. Proven exposure to the agent at one or more critical times during prenatal development. 2. Consistent findings by >/=2high-quality epidemiological studies. 3. Careful delineation of clinical cases; a specific defect or syndrome is very helpful. 4. Rare environmental exposure that is associated with a rare defect. 5. Teratogenicity in experimental animals. 6. Association should make biological sense.

15 Cauchemez et al. Lancet March 2016 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%.

16 29% of 42 pregnant women with confirmed Zika infection during pregnancy had adverse outcomes IUGR with or without microcephaly CNS abnormalities Fetal death at 36 and 38 weeks of gestation Brasil P et al. N Engl J Med March

17 Shepherd s Criteria 1. Proven exposure to the agent at one or more critical times during prenatal development. 2. Consistent findings by >/=2high-quality epidemiological studies. 3. Careful delineation of clinical cases; a specific defect or syndrome is very helpful. 4. Rare environmental exposure that is associated with a rare defect. 5. Teratogenicity in experimental animals. 6. Association should make biological sense.

18 Congential Zika Syndrome Severe microcephaly, Intracranial calcifications and other brain abormalities, Eye findings, Redundant scalp skin, Arthrogryposis Clubfoot.

19 Shepherd s Criteria 1. Proven exposure to the agent at one or more critical times during prenatal development. 2. Consistent findings by >/=2high-quality epidemiological studies. 3. Careful delineation of clinical cases; a specific defect or syndrome is very helpful. 4. Rare environmental exposure that is associated with a rare defect. 5. Teratogenicity in experimental animals. 6. Association should make biological sense.

20 ZIKV & Guillain-Barré syndrome (GBS) Table 1. Countries and territories in the Americas with GBS in the context of Zika virus circulation (as of 6 April 2016).

21 ZIKV & Guillain-Barré syndrome (GBS). The incidence of Guillain-Barré cases during the Zika epidemic in French Polynesia was 24 per population over the seven months of the epidemic, a rate significantly higher than the baseline incidence rate of 1to 4 per per year prior to the epidemic. Cao-Lormeau V-M et al. Lancet Feb 2016 Risk of GBS after ZIKV Case control study in French Polynesia revealed a strong association (odds ratio, >34) between Guillain Barré syndrome and previous Zika virus infection.

22 Acute Disseminated Encephalomyelitis (ADEM) In addition to autoimmune disease, some researchers also have reported patients with Zika infections developing encephalitis and myelitis nerve disorders typically caused by direct infections in nerve cells. Brazil, Dec 14 June 2015 Autoimmune disorders, n=6 - GBS 4 - ADEM 2 American Academy of Neurology (AAN) 2016 Annual Meeting. Emerging Science 004. Presented April 19, 2016.

23 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. It is possible that an investigational Zika vaccine will be ready to enter early-stage human trials in 2016.

24 Vector Control Strategies Wolbachia, Sterile insect technique (SIT), Genetically-modified mosquitoes, Attractive Toxic Sugar Baits, Lethal traps, and Long-lasting larvicides.

25 Resources

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