Clinical and Epidemiological aspects of Zika:What we know and what we don’t know

Maurício Lacerda Nogueira, MD, PhD

Associate ProfessorDepartment of Microbiology and Infectious Diseases

Faculdade de Medicina de São José do Rio Preto

mnogueira@famerp.br

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)

BURDEN OF ZIKA/DENGUEWhat are the real numbers?

THE CLINICAL EPIDEMIOLOGICAL DIAGNOSIS IN A OUTBREAK

Our experience with dengue AND ZIKA in SJRP

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”

Dengue in Zika “suspected”patients

All of them are in the official records as Zika cases…

(LANCIOTTI et al, 2008)

ZIKA Notified Patients

454 Samples

87 (19%) confirmed by qPCR

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)

Dengue in ZIKA notified patients

454 samples

52 (11,5%) positive by Multiplex-Nested-PCR

(LANCIOTTI et al, 2007)

CHKV in Zika notified patients

454 samples

1 positive

Sexo feminino

Arboviruses in ZIKA Notified patients

Zika

Dengue

CHK

Negative

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)

THE SPECTRUM OF THE DISEASEDeaths and Special populations

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

Acute Myelitis due to dengue infection

Estofolete et al. AJTM&H, in press

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

Causal Association Between Zika and Birth DefectsCase 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 1st trimester

exposure (Cauchemez, Lancet, 2016)

•OR 56 for association of Zika and

microcephaly (de Araújo, Lancet ID, 2016)

Evidence for Causality

(Rasmussen, NEJM 2014)

A ZIKA COHORT IN A DENGUE ENDEMIC AREA

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?

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

PROJETO VILA TONINHO

An arbovirus prospective cohort. Preliminary characterization

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

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Acknowledgment