Zika virus: clinical and epidemiological features
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1 Zika virus: clinical and epidemiological features Dominic Dwyer Medical Virologist, Westmead Hospital Director, ICPMR and Pathology West NSW Health Pathology
2 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
3 Zika virus Yap Island 2007 Brazil 2015 Zika 1947 French Polynesia 2013
4 New mosquito-borne Zika virus infections Jan 2013-Feb 2017 WHO Situation Report: Feb 2, 2017
5 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 Mar 3;10(3):e
6 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)
7 Predicted distribution of Aedes aegypti Kramer elife 2015
8 Molecular phylogeny of ZIKV in the Americas Faria NR et al. Science /science.aaf5036 (2016)
9 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):e , Wang L et al. Cell Host & Microbes 2016; 19:
10 ZIKV RNA in body fluids, and serum ZIKV-specific IgM, days after symptom onset ]* Paz-Bailey et al. NEJM, Feb 14, 2017
11 9.9 million visitors depart Brazilian airports annually 65% to Americas, 27% to Europe and 5% to Asia Bogoch Lancet 2016
12 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
13 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
14 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 /s x
15 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/ /journal.pmed
16 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 /science.aaf5036 (2016)
17 Timeline: Symptoms, Radiographic and Laboratory Studies Driggers RW et al. N Engl J Med DOI: /NEJMoa
18 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 weeks gestation CSF often normal cell count, protein
19 Zika virus microcephaly Estimated risk ~1% in the 1 st trimester congenital CMV after primary infection 18% congenital rubella % 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 % parvovirus B19 in pregnancy Cauchemez S et al. Lancet 2016 doi.org/ /s (16)
20 Congenital Zika Syndrome Moore CA et al. JAMA Pediatrics 2016:doi: /jamapediatrics
21 Cranial morphology in Congenital Zika Syndrome Moore CA et al. JAMA Pediatrics 2016:doi: /jamapediatrics
22 Brain findings in Congenital Zika Syndrome Moore CA et al. JAMA Pediatrics 2016:doi: /jamapediatrics
23 Microcephaly and arthrogryphosis in CZS Moore CA et al. JAMA Pediatrics 2016:doi: /jamapediatrics
24 Cohort study of pregnancy and rash in Rio, Brazil Brasil P et al. NEJM 2016;375:
25 Cohort study of pregnancy and rash in Rio, Brazil Brasil P et al. NEJM 2016;375:
26 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
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