Outbreaks of Zika Virus: What Do We Know? Presented by Dr Jonathan Darbro Mosquito Control Lab, QIMR Berhgofer 15 September 2016
Overview History Distribution Modes of Transmission Symptoms Some Causal Factors Where to from here QIMR Berghofer Medical Research Institute 2
Zika Virus Ashraf et al. 2015. Viruses 7(1): 219-238. QIMR Berghofer Medical Research Institute 3
First Contact with Zika Virus Isolated in 1947 from rhesus monkey 6.1% seroprevalence in Uganda First case 1953 (Nigeria) 1953-2006: 13 reported cases QIMR Berghofer Medical Research Institute 4
Areas in Which Zika Virus Infections in Humans Have Been Noted in the Past Decade (as of March 2016). Petersen LR et al. N Engl J Med 2016;374:1552-1563.
January 2016 vs. September 2016 (PAHO/WHO)
Case Count (Americas) Suspected Cases Confirmed Cases 494,784 116,122 Brazil, Puerto Rico, Colombia, Mexico Deaths 13 Brazil, Suriname, Puerto Rico Confirmed congenital syndrome 1950 Brazil, Colombia, USA PAHO/WHO 8 September 2016 QIMR Berghofer Medical Research Institute 7
Modes of Transmission Observed Mosquito bite Sexual Mother to child Theoretical (Virus Detected) Blood transfusion Tissue/organ transplant Breast Milk Urine Saliva Tears Laboratory exposure QIMR Berghofer Medical Research Institute 8
Zika Virus-Mosquito Transmission Cycle. Intrinsic incubation period (mosquito): 4-11 days Viraemic period (human): 3-5 days Petersen LR et al. N Engl J Med 2016;374:1552-1563.
Known Mosquito Vectors of Zika Urban Aedes aegypti Aedes albopictus Aedes hensilli (Yap) Aedes polynesiensis (F.P.) Sylvan (jungle) Aedes africanus Aedes luteocephalus Aedes furcifer Aedes taylori Ae. aegypti Ae. albopictus
Aedes aegypti Primary Zika vector Feeds on humans Tropical and subtropical climate Breeds in containers near human dwellings Also vector of dengue, chikungunya, yellow fever Bhatt et al. 2013. Nature 496: 504-507
Aedes albopictus Secondary vector Feeds on humans and other hosts Tropical, subtropical, temperate climate Breeds in containers near human dwellings Also vector of chikungunya, dengue Suspected vector of 22 viruses www.landcareresearch.co.nz
Sexual Transmission of Zika Virus First confirmed in 2008 Cases reported in 11 countries Mostly vaginal sex One anal sex transmission One transmission via vaginal fluid One asymptomatic transmission QIMR Berghofer Medical Research Institute 13
Sexual Transmission of Zika Virus Virus persistence in semen Virus titre as high as 100,000x blood serum As long as 41 days between onset of symptoms and index case Zika RNA detected as long as 188 days Virus persistence in vaginal fluid Less well known 5 days after symptom onset QIMR Berghofer Medical Research Institute 14
Most Zika Symptoms Similar to Dengue ~80% of cases asymptomatic Fever Rash Arthralgia Myalgia Retro-orbital pain Vomiting Conjunctivitis QIMR Berghofer Medical Research Institute 15
Zika Virus Infection Associated with Guillain-Barré Syndrome (GBS) Immune system attacks peripheral nervous system and damages myelin sheaths Symmetrical weakness or tingling sensation in legs, can spread to arms and upper body Incidence normally 1-4 per 100,000 Case control study from French Polynesia outbreak 41/42 GBS patients had anti-zika IgG or IgM 42/42 had neutralising antibodies (vs. 56% in control group) Cao-Lormeau et al. 2016. Lancet. 387(10027):1531-1539 QIMR Berghofer Medical Research Institute 16
Zika Virus and Congenital Microcephaly Reduction in brain volume motor disabilities speech impairment poor neurocognitive outcome behavioural issues Causes include: prenatal infections (e.g. rubella, cytomegalovirus, leptospirosis) maternal alcohol use hypertensive disorder Cauchemez et al. 2016. Lancet 387(10033): 2125-2132. QIMR Berghofer Medical Research Institute 17
Zika Virus and Congenital Microcephaly: Evidence Case-control study in French Polynesia found risk of microcephaly during first trimester was 95 cases per 100,000 (vs. 2 cases baseline) Complete ZIKV genome recovered from brain tissue of a fetus with microcephaly ZIKV found to infect human neural progenitor cells, causing cell death and attenuated hnpc growth. Cauchemez et al. 2016. Lancet 387(10033): 2125-2132. Mlakar et al. 2016. NEJM 374: 951-958. Tang et al. 2016. Cell Stem Cell 18: 1-4. QIMR Berghofer Medical Research Institute 18
Why Is There a Zika Outbreak? QIMR Berghofer Medical Research Institute 19
Why Is There a Zika Outbreak? Y? Mosquito distributions haven t changed QIMR Berghofer Medical Research Institute 20
Why Is There a Zika Outbreak? Y? Mosquito distributions haven t changed Has the virus changed? Three ZIKV strains (East African, West African, Asian) All outbreaks since 2007: Asian strain Asian strain has been gradually evolving and spreading since at least 1966 NS1 protein (Asian) appears to be better adapted to human cells (de Melo Freire, unpublished) QIMR Berghofer Medical Research Institute 21
Does the Chikungunya Outbreak Offer Any Clues? Coffey et al. 2014. Viruses 6(11): 4628-4663. QIMR Berghofer Medical Research Institute 22
Does the Chikungunya Outbreak Offer Any Clues? Three geographical strains West African East African Asian Similar movement pattern Same mosquito vectors Different virus family A226V mutation in ECSA CHIKV strain E. Africa Ae. albopictus Asian Ae. aegypti Patterns of Human movement? Commercial / travel QIMR Berghofer Medical Research Institute 23
Why Is There a Zika Outbreak? Y? Mosquito distributions haven t changed No evidence the virus has changed (yet) Human movement patterns a possibility Combination of naïve host population and vulnerable health infrastructure Teixeira 2012. Rev. Inst. Med. Trop. S. Paulo 54 QIMR Berghofer Medical Research Institute 24
Zika: Moving Forward Most likely will be established Studies on viral pathogenesis underway Vaccine trials imminent Larocca et al 2016. Nature 536: 474-478. Ae. aegypti population replacement with Wolbachia Render mosquitoes non virus-transmitting Aliota et al. 2016. Scientific Reports 6:28792. Conventional Aedes aegypti control critical Indoor residual spraying Larval source reduction QIMR Berghofer Medical Research Institute 25
Thank you www.qimrberghofer.edu.au