Shaping the Caribbean's response to Zika, UWI’s Zika Task Force (www.uwi.edu/zika) is gathering and providing expert advice to develop a strategic, scientific approach toward tackling the Zika virus.

1. ZIKA VIRUS IN THE AMERICAS
CHRISTINE CARRINGTON
DEPT. OF PRECLINICAL SCIENCES,
FACULTY OF MEDICAL SCIENCES,
THE UNIVERSITY OF THE WEST INDIES
ST. AUGUSTINE, TRINIDAD & TOBAGO

2. ZIKA VIRUS (ZIKV)
• Emerging arbovirus (arthropod-borne virus)
• Mosquito-borne
- Aedes aegypti (other Aedes spp. are potential vectors)
• Family Flaviviridae, genus Flavivirus
- enveloped, ssRNA genome
- e.g. Dengue, Yellow Fever, West Nile
• Two genotypes: African and Asian
Hayes EB. Zika virus outside Africa. Emerg Infect Dis. 2009 Sep
http://wwwnc.cdc.gov/eid/article/15/9/09-0442

3. ZIKA FEVER
• Short, relatively mild self-limiting febrile illness, usually
w/o severe complications or fatalities
- Apparent in about 20% of ZIKV infected individuals
- Symptoms develop 3-12 days after mosquito bite
- Rash, fever, joint / muscle pain, conjunctivitis (red eye)
- Low hospitalization rate
• No vaccine available
• Treatment is symptomatic - pain relief, antihistamines,
fever reduction
• Recent evidence suggest uncommon but serious side
effects of ZIKV infection

4. ORIGINS
Ancestral transmission cycle
(non-human primates & canopy
dwelling mosquito species)
Urban–periurban cycle
( Human & Aedes spp)
Spillover into human
population and adaptation to
anthropophilic Aedes spp.
• 1st isolated in 1947 from sentinel rhesus monkey from Zika Forest, Uganda.
• Animal reservoir still to be confirmed; likely to include non-human primates.
• Human population surveys at the time in Uganda found 6.1% antibody prevalence
• First human infection reported in Nigeria in 1954.

5. TRANSMISSION BETWEEN
HUMANS
• Aedes mosquito species.
- Primarily Ae. aegypti in tropical regions
- Virus also isolated from Ae. africanus, Ae. apicoargenteus, Ae.
luteocephalus, Ae. Vittatus, Ae. furcifer, Aedes hensilli, Ae.
Polynesiensis.
• Potential risk of ZIKV transfusion-derived transmission
• Perinatal transmission (transplacental; during delivery)
• Sexual transmission (some evidence; investigations underway)
- virus detected in semen
- A few documented cases of apparent transmission
- Not a major route

6. GLOBAL SPREAD
Source: WHO Zika virus, microcephaly and Guillain-Barre situation report, 26 Feb 2016

7. Ae. Aegypti endemic
No herd immunity
Large, dense populations (mainland)
Frequent human movement between countries

8. MICROCEPHALY
• Head circumference less than expected given average for age and sex
• Usually a result of the failure of the brain to develop properly
• Uncommon
• Causes:
- Genetic factors
• Down syndrome & other chromosomal disorders
• Inherited gene defects affecting brain development
- Environmental factors
• Inadequate nutrition
• Substance abuse
• Exposure to toxic chemicals or radiation
• Certain infections during development in the womb e.g. chicken pox, rubella
(German measles), cytomegalovirus.
PC: Felipe Dana/
AP Photo

9. EVIDENCE FOR A LINK BETWEEN ZIKV & MICROCEPHALY
AND/OR CENTRAL NERVOUS SYSTEM MALFORMATION
• Brazil
- 2001 to 2014: 163 reported cases per year
- Oct 2015 to Feb 2016: 5640 reported cases
- Microcephaly epidemic followed ZIKV spread
- ZIKV in amniotic fluids of microcephalic fetuses
- ZIKV detected in placental and fetal tissues (incl. brain) of stillborn / miscarried
fetuses with microcephaly / CNS malformation.
PC: Felipe Dana/
AP Photo
1533 fully
investigated
n = 950 n= 583
Met case definition of
microcephaly and/or
CNS malformation
associated with
congenital infection
Source: WHO Zika virus, microcephaly and Guillain-Barre situation report, 26 Feb 2016

10. EVIDENCE FOR A LINK BETWEEN ZIKV & MICROCEPHALY
AND/OR CENTRAL NERVOUS SYSTEM MALFORMATION
• French Polynesia
- Increase in microcephaly and CNS malformation case reporting following
epidemic (18 versus 0-2 per year previously).
• Other
- Cases (n = 2) in other countries linked to a stay in Brazil
PC: Felipe Dana/
AP Photo
Source: WHO Zika virus, microcephaly and Guillain-Barre situation report, 26 Feb 2016

11. WHY WASN’T APPARENT ASSOCIATION
WITH MICROCEPHALY NOTICED BEFORE?
Old World
• Virus endemic - herd immunity
• Different age group affected?
• Small rural populations?
• Surveillance?
New World
• Very large immunologically naïve population
• Very large number of people infected so rare consequences more
visible
• Increased awareness?

12. GUILLAIN-BARRÉ SYNDROME (GBS)
A rare autoimmune disorder
• damages the nerve cells leading to muscle weakness and sometimes,
paralysis.
• Symptoms can last weeks to months.
• most people fully recover but some people have permanent damage
and in rare cases, people have died.
Two thirds of people with GBS have experienced an infection
of some sort before the onset of the condition (usually
gastroenteritis or a respiratory tract infection).
Viruses known to trigger GBS include dengue viruses, West Nile
Virus, influenza virus…

13. ZIKA & GUILLAIN-BARRÉ SYNDROME
(GBS)
During 2015 and 2016, eight countries / territories reported
increased incidence and/or laboratory confirmation of ZIKV
infection among GBS cases.
Recent case-control study shows statistically significant
association between ZIKV infection and GBS.
Lormeau et al. 2016. Guillain-Barré Syndrome outbreak associated with Zika virus infection in
French Polynesia: a case-control study. The Lancet. Published online February 29, 2016
http://dx.doi.org/10.1016/S0140-6736(16)00562-6

14. ZIKV, MICROCEPHALY AND GBS
“Evidence that
neurological disorders,
including microcephaly
and GBS, are linked to
Zika virus infection
remains circumstantial, but
a growing body of clinical
and epidemiological data
points towards a causal
role for Zika virus”.

15. CDC, Division of Vector-Borne Diseases. Revised diagnostic
testing for Zika, chikungunya, and dengue viruses in US Public
Health Laboratories. February 7, 2016LAB DETECTION & DIAGNOSIS
Tests to detect virus
Tests to detect immune
response against virus
Cross-reactivity with other flaviviruses.
Sensitive and specific; but small
window for testing

16. ZIKV: HOW DOES IT COMPARE?
CHIKV DENV ZIKV
Classification Alphavirus Flavivirus Flavivirus
Clinical
Manifestation
Fever, arthralgia,
myalgia, rash
Fever, malaise, myalgia,
low platelet count
Fever, arthralgia, myalgia,
rash, conjunctivitis
Transmission Ae. agypti
Diagnosis RT-PCR during first week, immunoassay for anti-viral IgM>7 days
Management Painkillers
(NSAIDS avoided
if necessary),
rarely fatal, long
term sequelae
Acetaminophen and
fluids, fatalities in severe
cases, full recovery but
hospitalization may be
necessary
Painkillers (NSAIDS
avoided if necessary),
rarely fatal
Side effects?
Long term sequelae?

17. ZIKA VIRUS PREVENTION & CONTROL
For a healthy adult who isn't pregnant,
Zika doesn't pose much of a threat.
- Reduce mosquito population
- Reduce breeding sites
- Public education
- Protection against bites (bed nets, insect
repellants)
- Extra care for pregnant women
Prudent for pregnant women to be
cautious until more is known
- Avoid mosquito bites
- Avoid travel to high risk areas
- Delay pregnancy in high risk populations??
- Risk of sexual transmission??

18. MORE RESEARCH NEEDED
• Need more evidence to support causal link and asses risk
- Seroprevalence studies
- Case control studies
- Does ZIKV damage embryonic neural tissue?
- What % of fetuses get infected when mother infected?
- At what stage is the fetus most susceptible?
- Are there another cofactors involved (malnutrition? concurrent infection with
another virus? )
• Are there other neurological defects related to ZIKV infection?
• How long does ZIKV persist in semen?
• Rapid, sensitive and specific antibody test
• Vaccine?

19. REFERENCES
Centers for Disease Control and Prevention: Zika Virus (2016)
Pan American Health Organization: Zika Virus Infection (2016)
http://www.virology.ws/2016/01/28/zika-virus/
http://www.nature.com/news/zika-virus-brazil-s-surge-in-small-
headed-babies-questioned-by-report-1.19259
ECLAM report (English summary and conclusions ) -
http://www.nature.com/polopoly_fs/7.33594!/file/
NS-724-2015_ECLAMC-ZIKA%20VIRUS_V-FINAL_012516.pd
WHO Zika virus, microcephaly and Guillain-Barre situation report,
26 Feb 2016