Zika virus 2016

1. What We Need To Know:
ZIKA, DENGUE, CHK
Dr. Armando Torres Nieves
Infectious Diseases Specialist

2. 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!

3. 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

4. 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.

5. 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.

6. Pre Test Questions: And The
Answers Are..
• 1) C
• 2) C

7. 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!!!!

8. 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

9. 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”

10. 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”

11. 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!!!!

12. 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!!

13. ZIKA VIRUS PUERTO RICO
• Weeks 9-12, 2016
– 1024 presumptive cases
– Confirmed:
• DENV: 9
• CHIKV: 4
• ZIKV: 136

14. ZIKA VIRUS PUERTO RICO
• Cumulative 2016
– 3598 Presumptive cases
– Confirmed cases
• DENV: 74
• CHIKV: 25
• ZIKV: 426
• Flaviv: 9 (Pos IgM for ZIKV and DENV)

15. ZIKA VIRUS PUERTO RICO
• 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

16. 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

17. More About Flaviviruses
• Characteristics
– Common
• Size ( 40-65 nm)
• Symmetry
• Single stranded RNA
• 10-11k bases
• Appearance in electron microscope

18. 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

19. 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

20. FLAVIVIRUSES
• Non neurotropic viruses
– Hemorrhagic in humans
– Aedes species as vectors and primary hosts
• Eg ZIKA virus

21. 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

22. 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)

23. TRANSMISSION TO HUMANS
• 1) Mosquito bite (Aedes sp)
• 2) )Others
• ZIKA viral RNA detected in
– Blood semen, breast milk, urine, saliva, CSF, amniotic
fluid

24. TRANSMISSION TO HUMANS
• 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!

25. TRANSMISSION TO HUMANS
• 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

26. TRANSMISSION TO HUMANS
• Donor blood screening
– Travel or residence in areas of reported cases
within 4 weeks
– SX’s of possible active infection within last 14
days

27. 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

28. CLINICAL MANIFESTATIONS
• Others
– Retro orbital cephalea
– Myalgia
– Asthenia
• Rare
– Abd pain, nausea, diarrhea, mucus membrane
ulcerations, pruritus

29. CLINICAL MANIFESTATIONS
• 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

30. 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

31. 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

32. MICROCEPHALY
– Shepard’s scientific evidence criteria results
Based 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
risk
2) 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

33. 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

34. 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 virus
Unknown if virus acting alone or combined ( eg
DENV)

35. OTHER MANIFESTATIONS
• Ocular congenital manifestations due to
infection
– Macular atrophy
– Optic nerve anomalies

36. 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

37. 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

38. DIFFERENTIAL DIAGNOSIS
• Chikungunya
– Same sx’s
• Fever
• Intense joint pain (hands, knees, ankles)
– Disabling (Patient can’t walk)
• No conjunctivitis
• Coinfection has occurred
• Dx by serology

39. DIFFERENTIAL DIAGNOSIS
• Parvovirus
– Similar symptoms
• Acute symmetric arthralgia or arthritis
– Hands, knees, feet
• Rash could be present (not usual)
• Dx by serology

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

41. DIFFERENTIAL DIAGNOSIS
• Measles
• Leptospirosis
– Jaundice
– Conjunctival suffusion
– Fever, rigors, myalgia
• Group A Strep
• Malaria

42. 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)

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

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

51. 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

52. 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

53. 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

54. 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

55. 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

56. 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!

57. 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