Zika virus 2016

What We Need To Know:ZIKA, DENGUE, CHK

Dr. Armando Torres NievesInfectious Diseases Specialist

Pre Test Questions

• 1) Mr. J Inhofe traveled from Oklahoma to Puerto Rico and stood there at coastal San Juan hotel for 4 days, and sustained sex with a female partner who confessed having fever, arthralgia and and “looks as if she cried a lot”. His wife al Oklahoma tells him upon his arrival back to the US the good news that she thinks she’s pregnant!

Pre Test Questions

• 1) So apart of a couple of cana drinks to calm down, he comes for you for advise!

• You tell him that:– A) Wait at least one more week before sex since

virus lasts 7 days in blood– B) Wait 6 months since ZIKA infection induces

long lasting protection– C) No sex w/o male condom through her

pregnancy

Pre Test Questions

• 2) Mrs J Laurence visited Cuba for a period of 10 days and stood at La Habana and Varadero areas. She lives at Conn., US

• She was in her 6th week of gestation by then, and returned to the US 9 weeks ago, when she was told about this “ZIKA issue”

• She comes to you obligated by her mother for you as her OB/GYN MD to follow her pregnancy.

Pre Test Questions

• Apart of taking a deep breath, and accepting the challenge, your next approach to her after setting her in prenatal care routine is:– A) Order ZIKA IgM serum. If negative, no

further tests needed– B) Order ZIKA RT PCR and IgM serum. If

negative, US just at 28 weeks– C) Order ZIKA IgM serum. If neg, US at 20

and 28 wks.

Pre Test Questions: And The Answers Are..

• 1) C• 2) C

ZIKA VIRUS

• Cause of great concern Internationally• Has spread rapidly to the Americas and The

Caribbean• Similar pattern of Chikungunya spread

– Although usually asymptomatic or benign and short course of illness, strongly associated to Microcephaly, Fetal Death and Guillain Barre Syndrome!!!!

ZIKA VIRUS

• WHO – Declared ZIKA spreading explosively and

associated complications to be a public health emergency of international concern

• Many authorities advised– Pregnant women to consider postponing travel

to areas with ongoing transmission of ZIKA virus

ZIKA VIRUS

• Dr. Anne Schuchet. Deputy Director, CDC:“The Aedes mosquito vector of this

Zika virus is present in more US states than initially though.”– “What authorities are learning about the virus is

scarier than we initially though”

ZIKA VIRUS

• Dr. Tom Frieden, CDC Director:– “There’s no longer any doubt that ZIKA causes

infants to be born with abnormaly small heads and damaged brains”

– “The announcement marks a “turning point in the ZIKA outbreak”

– “Science now shows that ZIKA virus is the cause of tragic increase in microcephaly cases and other serious brain defects”

ZIKA VIRUS

• US: The White House will redirect $589 million in funds for and respond to Zika Virus before the carrier mosquito begins to emerge in continental US but they need more funding from the republican congress

• Republican controlled congress: – “The White House should draw the money

from $2.7 billion in funds for fighting Ebola!!!!

ZIKA VIRUS

• Puerto Rico– 7-9March2016

• CDC Dir DR Tom Frieden visited the island to personally supervise and assess the island’s authorities and citizens' preparedness and response to ZIKA

– Concerned about the number of cases confirmed in the island

– CDC expects exponential onset of new cases, up to several 100,000 as much!!

ZIKA VIRUS PUERTO RICO

• Weeks 9-12, 2016– 1024 presumptive cases– Confirmed:

• DENV: 9• CHIKV: 4• ZIKV: 136


• Cumulative 2016– 3598 Presumptive cases– Confirmed cases

• DENV: 74• CHIKV: 25• ZIKV: 426• Flaviv: 9 (Pos IgM for ZIKV and DENV)


• Cumulative ZIKV cases 2015-2016– Confirmed: 436 (Most cases in ages 20-64y/o)– Hospitalized: 8 (2%)– Pregnant: 60 (14%)

• Asymptomatic: 38 (63%)• Symptomatic: 22 (37%)• Guillain Barre Syndrome (GBS): 5 (1%)• Deaths: 0

Where This Virus Comes From?

• Family Flaviridae– Genus Flavi (Yellow in Latin), from Yellow

fever virus• Other “Flavi siblings”!

– West Nile Virus– Tick borne encephalitis virus– Dengue virus– Yellow fever virus– Other– All could cause encephalitis

More About Flaviviruses

• Characteristics– Common

• Size ( 40-65 nm)• Symmetry• Single stranded RNA• 10-11k bases• Appearance in electron microscope

More About Flaviviruses

• Transmission– Bite of infected arthropod (mosquito or tick)

• So these are “arbo”viruses (from arthro!) (ok!!)– Human infections, just incidental hosts

• Humans not effective replicating the virus to enough titers for infecting Aedes mosquitoes, except Dengue, ZIKA, CHKV viruses, well adapted for this

FLAVIVIRUSES

• Vectors– Ticks (Several I will not mention now!)– Mosquitoes

• Neurotropic virus containing– Encephalitis in humans and livestock– Usually Culex species as vector– Bird reservoirs

FLAVIVIRUSES

• Non neurotropic viruses– Hemorrhagic in humans– Aedes species as vectors and primary hosts

• Eg ZIKA virus

HISTORY OR ZIKA VIRUS

• Named after Ugandan forest where first virus isolated from Rhesus monkey (1947)

• Sporadic infections went to SE Asia• 2007-First mayor outbreak at Yap Islands

(Micronesia) > 70% population > 3y/o infected– 2013-2014-French Polynesia

• 32,000 people infected

HISTORY OF ZIKA VIRUS

• Feb 2014- Chile’s Eastern Island• May 2015-Brazil• Feb 2016- Caribbean (Dom Rep, Jamaica,

PR, Haiti, (not Cuba!! Humm)• Then Central and South America• No endemic cases in the US ( all travelers)

TRANSMISSION TO HUMANS

• 1) Mosquito bite (Aedes sp)• 2) )Others

• ZIKA viral RNA detected in – Blood semen, breast milk, urine, saliva, CSF, amniotic

fluid


• Sexual– Anecdotal reports

• Virus persist in semen up to 3 wks. after undetectable in blood

– Pending further studies of duration in semen

– Abstinence or male condom if inf men – If partner pregnant, barrier methods during

whole pregnancy for men!


• Blood donation/transfusion– ZIKA virus transmissible via blood products

and tissue transplants– No nosocomial cases documented

• Normal precautions are enough– If infected, defer blood donation x 4 weeks

before donation


• Donor blood screening– Travel or residence in areas of reported cases

within 4 weeks– SX’s of possible active infection within last 14

days

CLINICAL MANIFESTATIONS

• Occurrence in 20-25% or infected patients– Fever (37-38.5)– Macular rash– Arthralgia

• Small joints, hands, wrists, feet– Non purulent conjunctivitis– Clinical disease if > 2 of the above present


• Others– Retro orbital cephalea– Myalgia– Asthenia

• Rare– Abd pain, nausea, diarrhea, mucus membrane

ulcerations, pruritus


• SX’s since 2-12 days post mosquito bite– Usually mild– Resolve in 2-7 days– Viremia lasts 3-7 days, not more– Infection induces long-lasting protection– Hospitalizations rarely needed– Case fatality extremely rare

CLINICAL COMPLICATIONS

• Microcephaly – Definition

• Head circumference > 2 standard deviations below mean for sex and gestational age at birht

– Brazil (Mar2015-feb2016) > 5K cases newborns born to infected mothers with ZIKAV• Incidence 20x compared to previous years

MICROCEPHALY

• 13Apr2016 Dr Tom Frieden, dir CDC– No longer any doubt that ZIKAV inf causes

microcephaly, and it marks a “turning point in the ZIKA outbreak”

• Findings not based on piece of evidence; rather based in collection of clues of formal scientific rules for determining causality , or wether a given agent causes a disease

MICROCEPHALY

– Shepard’s scientific evidence criteria resultsBased on study data results

1) Had to show that exposure happened during critical window of development

Many babies exposed to ZIKAV in 1-2d trimester or pregnancy (brain still forming) at greatest risk2) To show that ZIKAV causes specific and repeating pattern of birth defects.

1) Brain damage (specific) in brain scans. Also extra skin on their scalps, eye damage, joint deformities

MICROCEPHALY

• 3)To show that rare exposure causes rare outcome– Rare cases of pregnant travelers who got ZIKA

inf gave birth to babies with microcephaly, (rare birth defect)

– Findings similar to population studies of Brazil and French Polynesia

– Virus has been obtained from ammiotic fluid, brain tissues (autopsy) and spinal fluid

MICROCEPHALY

• Risk of ZIKAV infection to pregnant women (How often fetus will develop birth defects?)– Current studies suggest between 1-29% or

babies born to infected mothers develop microcephaly

Unknown if some babies more vulnerable to virusUnknown if virus acting alone or combined ( eg DENV)

OTHER MANIFESTATIONS

• Ocular congenital manifestations due to infection– Macular atrophy– Optic nerve anomalies

OTHER MANIFESTATIONS

• Autoimmune Neurologic Conditions– Guillain Barre Syndrome

• Formerly seen assoc ZIKAV and GBS cases during French Polynesia outbreak

• 4 cases in Brazil– Acute disseminated encephalomyelitis (ADEM)

• 2 cases in Brazil• Hearing defects in newborns

DIFFERENTIAL DIAGNOSIS

• Dengue– No conjunctivitis– Severe sx’s share with ZIKA

• Fever, muscle pain, cephalea– Hemorrhagic– Dx by serology– Coinfection with ZIKAV and CHK described


• Chikungunya– Same sx’s

• Fever• Intense joint pain (hands, knees, ankles)

– Disabling (Patient can’t walk)• No conjunctivitis• Coinfection has occurred • Dx by serology


• Parvovirus– Similar symptoms

• Acute symmetric arthralgia or arthritis – Hands, knees, feet

• Rash could be present (not usual)• Dx by serology


• Rubella– Low grade fever– Coriza– Centrifugal rash from face to trunk/extremities– Arthritis– Lymphadenopathy


• Measles• Leptospirosis

– Jaundice– Conjunctival suffusion– Fever, rigors, myalgia

• Group A Strep• Malaria

Diagnosis

• Suspected cases– Maculopapular rash and/or

• Fever of 37-38.5C plus• Arthralgia• Arthritis• Conjunctivitis (dry)• Hx relevant epidemiologic exposure (cases

documented within last 4 weeks)

DIAGNOSIS

• Probable case– IgM titers positive against ZIKAV– Relevant epidemiologic exposure

DIAGNOSIS

• Confirmed case– Lab confirmation

• PCR (detection viral RNA)• Serum antigen• Both IgM positive and Plaque Reduction

Neutralization Test (PRNT) and PRNT90 ratio > 4x vs. other flaviviruses

DIAGNOSIS

• Non pregnant cases living in areas where mosquito transmission have been established, dx suggested by signs and symptoms (e.g. Puerto Rico)– Lab testing not necessary

• Non Pregnant cases in non endemic places to do lab tests if ZIKA like sx’s present

DIAGNOSTIC TESTS

• Definitive– RT PCR for ZIKA RNA or ZIKAV serology

• Pt.'s within 7 days post onset of SX’s• PCR positive during first 3-7 days

– Can’t exclude infection if >7 days– Also to be done for DENV and CHKV

DIAGNOSTIC TESTS

• Patients with >4 days post onset of sx’s– ZIKAV IgM– Neutralizing abs' titers >4x than DENV (serum)

• Useful for discrimination between cross reacting abx’s from other flaviviruses

• If inconclusive values, do convalescent titers in 2 weeks

DIAGNOSTIC TESTS

• Patients with 4-7 days post onset of sx’s– Do both RT PCR and Serology

• Lab testing for ZIKAV n/a commercially• Use Dept. of Health Protocol

– Covers expenses of testing

Evaluation of Pregnant Women

• Hx visit areas w/o mosquito transmission– Unprotected sex with patient c sx’s

• If neg hx, no lab testing needed• Hx relevant epidemiologic exposure or ill

– Lab testing within 2-12 wks. post exposure– Asx just serologic tests

• If neg after 2-12 wks., unlikely patient infected• Should undergo evaluation for fetal infection

FETAL EVALUATION

• Consists of serial US and or amniocentesis as needed

• Facts– As early as 18-20 weeks gestation

• Microcephaly• Intracranial calcifications

– Cerebellum, intraocular, brain• All seen more often during 3rd trimester

FETAL EVALUATION

• Screening schedule– Not indicated if no hx of ZIKAV exposure– Positive exposure

• Frequency of test according to lab results and presence or absence of symptoms

– If neg lab results prior to 20 wks. gestation» US at 20 and 28 wks.

– If neg lag results after wk. 20 do US 2 and 6 wks. later– If pos. US findings repeat serol testing and amniocentesis

FETAL EVALUATION

• If inconclusive lab results or sx. infection– And patient prior to 20 wks. gestation

• Serial US q 2-4 wks. starting at 18 weeks gestation• If inconclusive lab results or Sx infection

>20 weeks gestation– Serial US starts at time of dx

AMNIOCENTESIS FOR ZIKA RT PCR TESTING

• 15wks gestation– If ZIKAV exposure and inconclusive lab results

• Or pos. US with normal lab results• If fetal ventriculomegaly

• Specificity/sensitivity unknown– But + PCR in amniotic fluid considered

suggestive intrauterine infection• Useful guiding time of delivery and neonate level of

care at delivery. If (-) PCR, other cause of US changes

TREATMENT OF ZIKA

• Non specific– Rest– Fluids– Acetaminophen– Avoid ASA or NSAID’S (the later to minimize

risk premature closure ductus arteriosus in women with > 32 wks. gestation

ZIKA PREVENTION

• Personal protective measures – Prevention mosquito bite

• Long sleeves and pants, insect repellents• Stay indoors (screens, air conditioned)• Infected patients avoid being bitten by mosquitoes

• Environmental control– Eliminate potential mosquito breeding sites

• Avoid standing water, cover domestic water tanks

ZIKA PREVENTION

• Pregnant women– Same protective measures as non rest of people– Consider deferring to visit endemic ZIKA areas– Lactation

• No cases documented yet• Further studies needed

– No evidence fetus conceived after virus cleared from blood is at high risk; but don’t push it yet!

FINALLY…...

• PR Dept of Health issued press conference (8apr16)– For prevention sexual ZIKAV transmission

• ADM order #350– Health insurances to cover contraceptive products

» IUD’s and Insertion hormonal implants

– General prevention with the previously mentioned measures

– Telephones 911 and specially 311– www.911puertorico.com

Health & Medicine

Zika virus 2016