Zika virus in Brazil emergence and response

Carlos Magno C. B. Fortaleza, MD, PhD Department of Tropical Diseases

State University of São Paulo (UNESP)

São Paulo State Society for Epidemiology and Control of Healthcare-Associated Infections

NOTHING TO DISCLOSE

A WEIRD COINCIDENCE…

Zika – is a member of the virus (…) genus Flavivirus.(…) Its name comes from the Zika Forest of Uganda, where the virus was first isolated in 1947.

(Wikipedia)

Zica – Brazilian slang, meaning “bad luck” or “big trouble”.

(Portuguese online dictionary)

Presenting the problem… •  The greatest epidemics of Zika virus disease ever reported is going

on in Brazil.

•  Neurological complications are increasingly described in this seemingly mild disease.

•  WHO declared this event a Public Health Emergence of International Concern (February, 2016).

•  Mass gatherings are expected in Brazil in the following months, including the Olympic Games.

•  52 countries and territories report Zika (31 in the Americas).

THE DISEASE

Maculo-papular rash, conjunctivitis, headache and low grade fever Neurological complications (!?)

Zika – a flavivirus Sexual transmission!?

Aedes spp.

Paixão ES et al. Am J Public Health 2016; 106: 606-12.

Clinical picture

Challenges for Diagnosis •  Serological tests (IF and ELISA) show extensive

cross-reactivity with other flaviviruses, including Dengue and the Yellow Fever vaccine virus.

•  Detection of viral RNA (RT-PCR): –  Less than 5 days in blood –  More than 7 days in urine

Phylogeografic analysis linked Brazilian strains to close Polynesian ancestors

Zanluca C et al. Mem Inst Oswaldo Cruz. 2015;110:569–72 Musso D. Emerging Infect Dis 2015; 21: 1887

Malone RW et al. PLoS Neglect Trop Dis 2016; 10: e0004530 Imperato PJ. J Community Health 2016 (ahead of print)

Zika Virus Worldwide Spread

1947 Uganda

1954 Nigeria 1960s Malasia

2007 Yap isl 2014 Fr.Polynesia

2015 Brazil

THE COUNTRY

Upper Middle Income Country (World Bank) Estimated Population: 200 million people

Area: 8.5 million Km2 (3.3 million mi2)

Ocean Dry

frontier

Brazil Population Density (Kernel estimate)

Epicenter of Zika Epidemics

Climate ranging from humid equatorial to semi-arid

Lower Human Development Index (HDI)

Less access to basic satination

Northeastern Region

How did Zika virus reach Brazil?

World Soccer Cup, 2014? No affected country participated World Championship canoe race, 2014? Affected islands participating Tourism from Chile? Cases in Easter Islands in 2014.

Musso D. Emerging Infect Dis 2015; 21: 1887 Salvador FS, Fujita DM. Travel Med Infect Dis 2016; 1: 49-51

... into Brazil.

Estimated Zika virus infections in Brazil in year 2015

Difficulties: Lack of reliable serological tests, limited access to RT-PCR

Malone RW et al. PLoS Neglect Trop Dis 2016; 10: e0004530 Waggoner JJ, Pinsky BA. J Clin Microbiol 2016 (ahead of print)

... in Brazil ...

From Brazil...

Traveller’s returning from Brazil (September 2014 – August 2015) Total: 9.9 millions 65% to the Americas -  USA, 2.7 millions -  Argentina, 1.3 milions 27% to Europe -  Italy, 419 thousands -  Portugal, 411 thousands -  France, 409 thousands

-  5% Asia USA, Argentina and Italy have more than 60% of their population living in receptive areas.

Bogoch II et al. Lancet 2016; 387 (online)

COMPLICATIONS

Microcephaly

de Oliveira W et al MMWR 2016; 65;242–247

> 3 SD > 20 SD Increase over baseline incidence

Cases in States with increases over 20 SD

Pernambuco

Paraíba

Bahia

2015

•  Relevant temporal association in Brazil –  60%-70% of mothers reported rash during pregnancy

Miranda-Filho DB et al. Am J Public Health 2016; 106: 598-600

•  Fetus autopsy and in vitro models of neurogenesis Mlakar J et al. N Engl J Med 2016;374:951-8

Tang H et al. Cell Stem Cell 2016 (ahead of print)

•  Fetal abnormality in 12 out of 42 ZIKV (+) pregnant women

Brasil P et al. N Engl J Med 2016 (DOI: 10.1056/NEJMoa1602412)

•  Relevant temporal association in Brazil –  60%-70% of mothers reported rash during pregnancy

Miranda-Filho DB et al. Am J Public Health 2016; 106: 598-600

•  Fetus autopsy and in vitro models of neurogenesis Mlakar J et al. N Engl J Med 2016;374:951-8

Tang H et al. Cell Stem Cell 2016 (ahead of print)

•  Fetal abnormality in 12 out of 42 ZIKV (+) pregnant women

Brasil P et al. N Engl J Med 2016 (DOI: 10.1056/NEJMoa1602412)

HOWEVER •  Pre-epidemic rates probably underestimated

–  USA and UK, 1-2 per 10,000 births / Brazil, 0.5 per 10,000 births Schuler-Facini L et al. MMWR 2016; 65: 59-62

•  Conflicting definitions may have overestimated current rates Victora CG et al. Lancet 2016 (online)

Guillain-Barré Syndrome…

FRENCH POLYNESIA

Incidence: 0.24 case per 1,000 infections

Case-control (P<0.001):

GBS – 100% ZIKV (+) Controls – 56% ZIKV (+)

BAHIA STATE, BRAZIL

Incidence (preliminary): 1 case per 1,000 infections (?)

Paixão ES et al. Am J Public Health 2016; 106: 606-12

Cao-Lormeau et al. Lancet 2016 (online)

… plus myelitis, encephalitis, etc.

THE RESPONSE

An agenda to fight Zika

1.  To enlarge the basis of evidence on vulnerability. “Move from case reports to case-control” (*)

2.  To develop a fast and reliable serological test. 3.  To control infestation with Ae. aegypti, possibly with the use of

novel biotechnology.

4.  To establish protocols of care, with emphasis on affected pregnant women and newborns.

5.  To start the groundwork for a vaccine.

6.  To reprogramme healthcare system.

Barreto ML et al. Lancet 2016; doi: 10.1016/S0140-6736(16)00545-6

(*) Musso D, Baud D. Lancet Infect Dis 2016; doi 10.1016/ S1473-3099(16)00096-7

Intensification of vector control

Extensive media campaing

Epidemiological office for mass gatherings and emergencies

Financial support for research in prevention and control

Sources: Brazil Ministry of Health / São Paulo State Health Department

Safety in Mass Gathering “The Dengue analogy”

Olympic Games

In Conclusion •  The Zika epidemics if a

worldwide concern. It is still a greater threat for pregnant women.

•  Even though many Brazilian states report autochtonous cases, the disease is not equally spread.

•  Brazil has started intense measures for fighting the spread of the disase.

ACKNOWLEDGEMENTS

APECIH Delegates (University of São Paulo) Sílvia Figueiredo Costa, Ícaro Boszczowski

Ministry of Health, Brazil

Cláudio Maierovich P. Henriques

São Paulo State Health Department Marcos Boulos, Alice Tiago

THANK YOU Email: cmfortaleza@uol.com.br

Email: cmfortaleza@uol.com.br