Zika virus: clinical and epidemiological features Dominic Dwyer Medical Virologist, Westmead Hospital Director, ICPMR and Pathology West NSW Health Pathology dominic.dwyer@sydney.edu.au,
Zika virus Flavivirus first isolated in 1947 in a rhesus monkey in the Zika forest, Uganda enveloped RNA virus ~11 kb closely related to dengue, yellow fever, Japanese encephalitis, Murray Valley encephalitis viruses
Zika virus 1947-2016 Yap Island 2007 Brazil 2015 Zika 1947 French Polynesia 2013
New mosquito-borne Zika virus infections Jan 2013-Feb 2017 WHO Situation Report: Feb 2, 2017
Zika virus ecology Mammalian Hosts Africa: primate-mosquito cycle with low endemic activity and occasional epidemics Asia and Americas: possible sylvatic cycles involving primates (orangutans, capuchins etc) Human-mosquito cycle Mosquito vectors Aedes aegypti is the dominant vector French Polynesia, New Caledonia, Americas, Africa Others: Aedes albopictus (Gabon, Africa), Aedes hensilli (Yap), Aedes polynesiensis (French Polynesia) Other species but less important (Aedes luteocephalus, Aedes vittatus) Aedes africanus in the sylvatic cycle in Africa Chouin-Carneiro T et al. PLoS Negl Trop Dis. 2016 Mar 3;10(3):e0004543
Zika virus transmission arthopod-borne via Aedes spp. (Aedes aegypti) mosquitoes mother to child sexual transfusion (needlestick/laboratory acquired, non-sexual direct contact) (potential - transplantation, saliva, breast milk)
Predicted distribution of Aedes aegypti Kramer elife 2015
Molecular phylogeny of ZIKV in the Americas Faria NR et al. Science 10.1126/science.aaf5036 (2016)
Zika virus At least two Asian lineages with spread to the Pacific and Americas Yap 2007, Singapore 2016: Asian lineage virus similar to Malaysian (1967) and recent Thai strains French Polynesia: Asian lineage virus closer to the Cambodian 2010 than to the Yap 2007 strain Recent evolution of American lineage/sublineage Epidemiological markers or significant biological change? ZIKV strains from Asia and the Americas show N-linked glycosolation of ASN-154 in the E protein, which has been associated with neuroinvasiveness in West Nile virus. Not present in most African strains. Several prm coding sequence mutations in Asian/Americas strains possibly increase pathogenicity NS1 mutations in human brain isolate from Brazil Possible adaptations to increased replication in Aedes aegypti in Americas May M et al. PLoSONE 2016; 11(9):e0161355, Wang L et al. Cell Host & Microbes 2016; 19:561-565
ZIKV RNA in body fluids, and serum ZIKV-specific IgM, days after symptom onset ]* Paz-Bailey et al. NEJM, Feb 14, 2017
9.9 million visitors depart Brazilian airports annually 65% to Americas, 27% to Europe and 5% to Asia Bogoch Lancet 2016
Zika: clinical picture typical rash, fever, conjunctivitis, arthralgia and arthritis headache, retro-orbital pain, myalgia etc hospitalisation uncommon asymptomatic true rate? (quoted ~80% in Yap outbreak, but 38% Zika-IgM seropositive were symptomatic) 1:1 asymptomatic:symptomatic in French Polynesia complicated congenital Zika syndrome neurological Duffy MR et al, NEJM 2009;360:2536, Aubry M et al, EID 2017 in press
Clinical picture - neurological disease Guillain-Barré syndrome (GBS) acute inflammatory demyelinating polyneuropathy type other variants estimated 0.24/1000 cases (Tahiti*) shorter onset (median 6-7 days) *Cao-Lormeau et al, EID 2014;20:1085 Parra B et al, NEJM 2016;375:1513
Clinical picture - neurological disease acute myelitis meningoencephalitis/seizures retinitis/uveitis/chorioretinal atrophy/maculopathy/papilloedema hearing loss congenital Zika syndrome Duca LM et al. Curr Infect Dis Rep 2017DOI 10.1007/s11908-017-0557-x
Zika virus in pregnancy Miscarriage Stillbirth Alive microcephalic baby Abnormal baby Normal baby, infected Normal baby, uninfected Normal baby, post-natal infection Krauer F et al. PLoS Medicine 2017 doi.org/10.1371/journal.pmed.1002203
Time series and cartography of reported ZIKV infections and microcephaly cases in Brazil Weekly ZIKV notifications in 5596 municipalities in Brazil (n=2791 cases) ZIKV cases/100,000 people in each state Suspected microcephaly cases/100,000 people in each state Faria NR et al. Science 10.1126/science.aaf5036 (2016)
Timeline: Symptoms, Radiographic and Laboratory Studies Driggers RW et al. N Engl J Med 2016. DOI: 10.1056/NEJMoa1601824
Zika virus microcephaly Brain development arrest Intracerebral calcifications, astrogliosis Reduced parenchymal volume Ventricular enlargement Cortical, subcortical and retinal atrophy No brain destruction (necrosis) Mainly at 20-28 weeks gestation CSF often normal cell count, protein
Zika virus microcephaly Estimated risk ~1% in the 1 st trimester congenital CMV after primary infection 18% congenital rubella 38-100% 10% adverse fetal outcomes in parvovirus B19 But High Zika virus attack rates (66-73% in Pacific) CMV in pregnancy 1-4% congenital rubella rare 0.61-1.24% parvovirus B19 in pregnancy Cauchemez S et al. Lancet 2016 doi.org/10.1016/s0140-6736(16)00651-6
Congenital Zika Syndrome Moore CA et al. JAMA Pediatrics 2016:doi:10.1001/jamapediatrics.2016.3982
Cranial morphology in Congenital Zika Syndrome Moore CA et al. JAMA Pediatrics 2016:doi:10.1001/jamapediatrics.2016.3982
Brain findings in Congenital Zika Syndrome Moore CA et al. JAMA Pediatrics 2016:doi:10.1001/jamapediatrics.2016.3982
Microcephaly and arthrogryphosis in CZS Moore CA et al. JAMA Pediatrics 2016:doi:10.1001/jamapediatrics.2016.3982
Cohort study of pregnancy and rash in Rio, Brazil 2015-16 Brasil P et al. NEJM 2016;375:2321-34
Cohort study of pregnancy and rash in Rio, Brazil 2015-16 Brasil P et al. NEJM 2016;375:2321-34
Traveller advice Mosquito advice/control Prevention as no antivirals or vaccine Smart Traveller (DFAT) High/moderate/low risk based on widespread/sporadic/historical transmission Reconsider travel to ZIKV regions if pregnant Testing on return Symptomatic/asymptomatic Management of pregnancy/sexual transmission