1. Zika in Latin America
Jimmy Whitworth Department of Infectious Disease Epidemiology WCFSJ October 2017
Improving health worldwide

2. Zika virus epidemic in latin America 2015-2017
75 countries have reported recent transmission,
WHO estimates 478,000 cases in 2016; 31,000 in 2017 (Jan-Jun)
Spread beyond Latin America: Florida & Texas, Singapore, SE Asia
WHO declared PHEIC Feb-Nov 2016
complications:
Guillain-Barre syndrome.
Congenital Zika Syndrome (microcephaly). Over 1900 confirmed cases
Risk estimates of CZS vary from 6% (USA) to 46% (Brazil)
Risk estimates of microcephaly 3-4% (10-11% in first trimester)

3. Zika virus Flavivirus (like dengue, yellow fever, west nile)
Main life cycle in Africa:
Aedes mosquitos and monkeys,
Humans are occasional hosts.
Original African lineage, subsequent Asian lineage
Asian lineage in latin America
Primary vector in urban settings: Aedes aegypti
Competent vector: Aedes albopictus (and other species)
Other routes of transmission:
Trans-placental (mother to child)
Sexual
Blood transfusion (also needlestick)
Day-biting mosquito

4. Zika First isolated 1947 from rhesus monkey, Zika forest, Uganda 14 human cases reported up to 2007
Red: isolated from humans
Yellow: human antibodies
Green: isolated from mosquitos
Hayes E B. Emerg Infect Dis Sep;15(9):

5. Zika timeline: global

6. Zika timeline: the Americas
Why is this important?
Zika epidemic like this never seen before
Affects mothers and unborn children
Olympics?

7. Clinical presentation
Most infections have no symptoms (80%)
Non-specific viral illness
Lasts less than 1 week
Itchy rash, headache, muscle and joint pains, red sore eyes, mild fever
Similar presentation to dengue (flavivirus) and Chikungunya
These are also circulating in Brazil
Diagnostic tests unreliable
Blood tests of exposure cross-react with dengue, yellow fever vaccine, malaria
Blood tests of infection insensitive after first week or two
How reliable are the numbers of cases reported?

8. Emergency Committee convened by the Director-General under the
Emergency Committee convened by the Director-General under the International Health Regulations (2005) held 1 February 2016
“Recent cluster of microcephaly cases and other neurological disorders reported in Brazil, following a similar cluster in French Polynesia in 2014, constitutes a Public Health Emergency of International Concern”
WHO statement 14 April 2016:“Based on a growing
body of research there is scientific consensus that
Zika virus is a cause of microcephaly and other
congenital anomalies and Guillain-Barre syndrome”

9. Association or causation?
Microcephaly cases occurring in same place and at same time as zika cases. Association
Zika could be causing microcephaly or it might be due to something completely different – eg pesticides, water contamination
Causation:
Zika infection at time of pregnancy consistent with defects observed (CMV, Rub, Tox)
Specific characteristics in babies with confirmed zika infection
Biological plausibility, zika kills brain cells
Zika isolated from brains of affected babies
This makes causation likely but does not prove it.
Still room for other theories

10. 29% of Brazilian municipalities reported at least one case in 2015
Spatial distribution of suspected notified cases of microcephaly by municipality
Nov
739
(738 NE)
Jan
3530 (3130 NE)
May
7438
(5706 NE)
Mid Aug
9015
(6330 NE) 1
29% of Brazilian municipalities reported
at least one case in 2015

11. Congenital infections
“Congenital Zika syndrome”: wider than microcephaly alone.
Similarities with rubella and other congenital infections
Cases range in severity; some babies have neurological abnormalities
with normal head circumference.
Some babies born normal size but do not grow.
Small heads
Constant irritability and crying
Spasms and seizures
Eye and ear defects
Swallowing defects
What happens when the babies get older?
ZIKV Infection in Pregnant Women in Rio de Janeiro — Preliminary Report
A report from the follow up of a cohort of pregnant women with rash illness was published in the past week.  Preliminary findings suggest that ZIKV infection during pregnancy appears to be associated with serious outcomes, including fetal death, placental insufficiency, fetal growth restriction, and CNS injury

12. Control measures Focus is on preventing transmission
Vector control: breeding sites, personal protection, biological and genetic control of mosquitos
Advice: pregnancy, sex, blood products
There is no vaccine or specific antiviral treatment
Symptomatic treatment only
Vaccines under development but years until clinical deployment

13. Vaccines Prevent infection, do not cure infections
Specific for each infection (like an artificial infection)
Creates artificial immunity
May need multiple doses to boost immunity
Usually take many years to develop
Cell studies, toxicity, animal studies
Human studies – small numbers: safety and dose, then larger numbers to prove they are effective.
Needs natural challenge from infection to prove it works!

14. Zika vaccine
2015 – nothing!
But work on related flaviviruses: dengue, West Nile
Existing animal models, immune assays, vaccine designs
13 weeks to first in-human trial
Now most advanced vaccine in intervention trial (2400 people)
US, Peru, Brazil, Costa Rica, Panama, Mexico
Few cases now, so hard to test.
Need natural transmission causing real cases to prove vaccine works.

15. What has happened during this outbreak?
With no vaccine and limited vector control measures epidemic will stay in latin America until it exhausts the pool of susceptibles: estimated that epidemic will be over within 3 years
Confirmed cases in Brazil
2015 – 141,000
2016 – 478,000
2017 – 31,000 (Jan-Jun)
In Salvador (NE Brazil) 60% have evidence of zika exposure, also 75% dengue and 5% chikungunya
Epidemic has infected up to 2 million child-bearing women
10 s of thousands of babies could be affected
How has birth rate been affected by outbreak?
What is the risk at different stages of pregnancy?
Challenge for society and health services in Americas:
Support and linkage to care
Babies and their families

16. Epidemic of scientific papers
As numbers of cases of zika exploded so did the numbers of zika scientific papers
Are they important?
Studies on cells, animals, models, people
Number of people – the more the better
Type of study:
case report, case series, case-control, cohort, controlled trial
Journal, or press release?
Peer reviewed?

17. What will happen next?
Zika still present, but much reduced. Mostly affecting populations at northern (Mexico) and southern (Uruguay, Argentina, Chile, southern Brazil) margins,
If reported numbers are reliable, epidemic is now over until enough children are born to sustain a new outbreak: probably over 10 years until next major epidemic
It may move on. WHERE?
Vector competence and density
all of tropics and subtropics potentially at risk
Potential distribution of Ae aegypti

19. Guillain-Barré Syndrome
Increase in neurological and auto-immune conditions reported: mainly Guillain-Barré syndrome
Rapid onset muscle weakness, starts in hands & feet and spreads
Immune damage to peripheral nerves
Rare complication of gastrointestinal or respiratory infections, also seen with dengue
Can be life-threatening if affects breathing muscles
Lasts about 1 week, most make full recovery
Supportive care, ventilation
Risk 0.24 cases/1000 infections (French Polynesia 2013/14)
Consistent with risk after campylobacter
GBS reported after zika in 14 countries
Guillain-Barré syndrome (GBS) is an autoimmune condition in which the individual’s immune system inappropriately attacks components of their peripheral nerves. This results in muscle weakness in the legs and/or arms, which can spread to other parts of the body.
GBS occurs worldwide but is a rare condition with an overall incidence of 0.4 to 4.0 per 100,000 people per year (WHO factsheet, 2016). People of all ages can be affected, but it is more common in adults and males.
It is believed that GBS occurs when antibodies produced in response to an infection cross-react with peripheral nerve components, through molecular mimicry. Less commonly, GBS may be triggered by immunisation, surgery, trauma or bone marrow transplantation.

20. Why did zika emerge? Several non-exclusive hypotheses:
Zika has evolved for enhanced mosquito transmission
(seen in Chikungunya)
Asian Zika has adapted for higher viraemia in humans
(vertical transmission, neuropathology)
Introduction into a naïve population susceptible to infection
Previous exposure to Dengue may exacerbate Zika disease
(some evidence, 43% amino acids identical)
Human genetic predisposition in latin America
Shan et al., An Infectious cDNA Clone of Zika Virus to Study Viral Virulence, Mosquito Transmission, and Antiviral Inhibitors, Cell Host & Microbe (2016 in press),