Clinical and Epidemiological aspects of Zika: What we know and what we don t know

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1 Clinical and Epidemiological aspects of Zika: What we know and what we don t know Maurício Lacerda Nogueira, MD, PhD Associate Professor Department of Microbiology and Infectious Diseases Faculdade de Medicina de São José do Rio Preto mnogueira@famerp.br

2 WHAT ARE THE KEY POINTS IN THE CLINICAL EPIDEMIOLOGICAL ASPECTS OF ZIKA? The real burden of the disease The spectrum of the disease Special populations The epidemiological aspects of the disease The GBS/Microcephaly pathogenesis The epidemiological aspects of The GBS/Microcephaly (including co-factors)

3 What are the real numbers? BURDEN OF ZIKA/DENGUE

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5 Our experience with dengue AND ZIKA in SJRP THE CLINICAL EPIDEMIOLOGICAL DIAGNOSIS IN A OUTBREAK

6 We tested 100 patients with Dengue at the ER - 45% is dengue, but All of them are officially Dengue in the SINAM system by Clinical Epidemiological criteria

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10 All of them are in the official records as Zika cases Dengue in Zika suspected patients

11 ZIKA Notified Patients 454 Samples 87 (19%) confirmed by qpcr (LANCIOTTI et al, 2008)

12 Dengue in ZIKA notified patients 454 samples 52 (11,5%) positive by Multiplex-Nested-PCR Figura. Gel de agarose exibindo padrões genéticos de isolados de DENV-1 (472 pb), DENV-2 (316 pb) e DENV-4 (222 pb) por M-N-PCR. Colunas: C1, padrão de peso molecular (100 pb); C2, DENV-4; C3, DENV-2; C4 a C7, DENV- 4; C8, DENV-1; C9, DENV-4; C10, controle negativo. (BRONZONI et al, 2005)

13 CHKV in Zika notified patients 454 samples 1 positive Sexo feminino (LANCIOTTI et al, 2007)

14 Arboviruses in ZIKA Notified patients Zika Dengue CHK Negative

15 Burden of Zika/Dengue We don t know the real burden of Zika/Dengue/CHKV in Brazil The clinical-epidemiological criteria is not good enough with co-circulation of 3 arboviruses (maybe more WNV, SLEV). We don t now the denominator for most of the indicators that we want. In order to overcome it epidemiological studies needs to be carried out (expensive)

16 Deaths and Special populations THE SPECTRUM OF THE DISEASE

17 Zika in new presentations Very mild dengue-like disease Only a few hundred cases had been described before 2015 Deaths? Atypical Manifestations? Special population: immunosuppressed, AIDS, etc?? Microcephaly was not described before

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22 Acute Myelitis due to dengue infection Estofolete et al. AJTM&H, in press

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24 Zika in new presentations The large number of cases will show the complete spectrum of the disease Deaths? ( with Zika or because Zika?) Atypical Manifestations Special population: immunosuppressed, AIDS, etc. Microcephaly

25 Causal Association Between Zika and Birth Defects Case Reports Zika detected fetuses w/ abnormalities (Oliveira Melo, Uts Ob Gyn 2016) Autopsies of aborted fetuses, stillbirths (Mlakar, NEJM, 2016, Martines, MMWR 2016) Hydrops fetalis and fetal demise (Sarno, PLoS NTD, 2016) Epidemiological Studies 29% adverse fetal outcomes among pregnant women (Brasil, NEJM, 2016) 1% risk of microcephaly after 1 st trimester exposure (Cauchemez, Lancet, 2016) OR 56 for association of Zika and microcephaly (de Araújo, Lancet ID, 2016) Evidence for Causality (Rasmussen, NEJM 2014)

26 A ZIKA COHORT IN A DENGUE ENDEMIC AREA

27 What do we know about Zika after 1 year Zika causes a very mild diseases in adults (we knew that before) Zika can cause damage to CNS (This potential is well known in flavivruses ) Zika is linked with GBS ( we knew that before with less evidence) Zika causes microcephaly, but what co-factor?

28 What we DON T know about Zika after 1 year What is the real spectrum and burden of Zika in adults and children? What is the precise role of Zika in CNS damage? What are the risk factors for GBS and the real role of Zika (and other flavivirus)? What are the risk factors, the epidemiological data and the precise role of Zika in microcephaly? What are the role of other potential vectors in Zika circulation and other routes of transmission? We don t know the basic epidemiological data about Zika

29 PROJETO VILA TONINHO An arbovirus prospective cohort. Preliminary characterization

30 PROJETO Vila Toninho Designed as a 2000 people general population cohort in order to study dengue epidemiology Funded by FAPESP and SUCEM Started in 2015 First enrollment in September (~1500 patients in the first year) Uses UBS, PSF and UPA Active and passive surveillance Human and vector First year follow up is ongoing right now Low levels of ZIKAV circulation in the first year (only 1 lab confirmed case). 6% IgG (preliminary) 65% for Dengue

31 Acknowledgment 31