Zika Virus in the Americas

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

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

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

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.

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

GLOBAL SPREAD

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

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

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

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.


1533 fully investigated

n = 950 n= 583 Met case definition of microcephaly and/or CNS malformation

associated with congenital infection


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



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?

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…

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

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”.

CDC, Division of Vector-Borne Diseases. Revised diagnostic testing for Zika, chikungunya, and dengue viruses in US Public

Health Laboratories. February 7, 2016

LAB 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

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?

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??

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?

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

Health & Medicine

Zika Virus in the Americas