1/24/2017
1
Zika UpdateChristine Hahn, MDIdaho Division of Public Health
Petersen LR et al. N Engl J Med 2016;374:1552-1563.
Zika Virus Transmission Cycle.
1/24/2017
2
Petersen LR et al. N Engl J Med 2016;374:1552-1563.
Infants with Moderate or Severe Microcephaly Associated with Maternal Zika Virus Infection, as
Compared with a Typical Newborn.
Zika: origins and spread
Source: WHO and Lancaster University
Nigeria: 1960
1970s: India, Pakistan
2007: Micronesia
2013: French Polynesia
2014: Brazil
2016
1/24/2017
3
Why were the harmful effects unknown until now?
• Not clear, but there appears to be little genetic difference among the various strains.
• Experimental work in mosquitoes suggests that the virus was capable of causing detrimental health effects and outbreaks all along.
• It is likely that scientists and health officials did not understand Zika’s potential because the virus circulated mostly in remote locations until the past few years.
Zika: the initial picture
• No FDA-approved vaccines
• For exposure: no FDA-approved prophylaxis
• No commercially available FDA-approved tests but several tests quickly developed
• EUA: Zika MAC-ELISA (CDC); Triplex rRT-PCR (CDC); Zika Virus RNA Qualitative Real-Time RT-PCR (Focus Diagnostics Inc); RealStart Zika Virus RT-PcR (altona Diagnostics GmbH); Aptima Zika Virus assay (hologic, Inc); Viracor-IBT Laboratories Zika Virus Real-time RT-PCR (Viracor-IBT); VERSANT® Zika RNA 1.0 Assay (kPCR) Kit (Siemens Healthcare Diagnostics Inc.); xMAP® MultiFLEX™ Zika RNA Assay (Luminex Corporation); ZIKV Detect™ IgM Capture ELISA (InBios International, Inc.); LightMix® Zika rRT-PCR Test (Roche Molecular Systems, Inc.); Sentosa® SA ZIKV RT-PCR Test (Vela Diagnostics USA, Inc.); Zika Virus Detection by RT-PCR (ARUP Laboratories)
• No treatment
Source: http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMIssues/ucm485199.htm#eua
1/24/2017
4
Zika Manifestations
• Most (80%) asymptomatic.
• Characteristic clinical findings are acute onset of fever with maculopapular rash, arthralgia, or conjunctivitis. Clinical illness is usually mild with symptoms lasting for several days to a week.
• Severe disease requiring hospitalization is uncommon and case fatality is low (recent Utah death).
• Guillain-Barré syndrome reported in patients following suspected Zika virus infection.
• Microcephaly and other severe fetal brain defects.
Blood Donors
1/24/2017
5
Pregnant Women
• Avoid travel to area with active Zika virus transmission
• Barrier protection for duration of pregnancy if partner lives in or has traveled to an area with Zika
TESTING:
• If exposed and asymptomatic, may offer IgM within 2-12 weeks after last date of possible exposure.
• If exposed and symptomatic, rt-PCR test serum AND urine
• up to 2 weeks after symptom onset, or
• if they are in the 2-12 week window and IgM positive.
Persons of reproductive age trying to conceive
• Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Persons with Possible Zika Virus Exposure — United States, September 2016. MMWR Early Release / September 30, 2016 / 65
• Consider avoiding nonessential travel to areas with active Zika virus transmission
• Women possibly exposed should wait at least 8 weeks from symptom onset (if symptomatic) or last possible exposure (if asymptomatic) to attempt conception.
• Men with possible Zika virus exposure, regardless of symptom status, should wait at least 6 months from symptom onset (if symptomatic) or last possible exposure (if asymptomatic) before attempting conception
1/24/2017
6
Zika: how big a health threat?
Petersen LR et al. N Engl J Med 2016;374:1552-1563.
Approximate Ranges of A. aegypti and A. albopictus in the United States (as of March 2016).
1/24/2017
7
Lancet Feb 2016
Reported on GBS cases observed during outbreak of Zika in French
Polynesia October 2013 - April 2014
42 cases of GBS
41/42 had anti-Zika IgM or IgG
100% had neutralizing Ab vs. 56% in control group without GBS
electrophysiological findings compatible with acute motor axonal
neuropathy type of GBS
Source: the Lancet, 2/2016
Columbia’s first cases of Zika reported October 2015
Study group is following pregnant women with Zika dx
Initial subgroup of 1,850 pregnant women:
> 90% of women infected during the 3rd trimester had given birth
no infants with apparent abnormalities identified
majority of the women who contracted Zika in the 1st or 2nd trimester still
pregnant at the time of publication
Additionally, 50 microcephaly cases were investigated to determine cause; of
these, 24 had etiology determined
20 other infections including STORCH (syphilis, toxoplasmosis, other (e.g.
VZV, parvovirus B19), rubella, CMV, HSV
4 Zika– moms all asymptomatic during pregnancy
Source: NEJM, Jun 15 2016
1/24/2017
8
Increased numbers of GBS reported in late 2015-2016
68 patients with GBS evaluated
66 had prior or current Zika-compatible illness
50% had bilateral facial paralysis; ascending limb weakness also seen
78% had acute inflammatory demyelinating polyradiculoneuropathy type of
GBS
17/42 (40%) patients tested by PCR were positive for Zika
Source: NEJM, 10/20/2016
Study followed 345 pregnant women presenting with rash; 182 tested positive for Zika
134 Zika-impacted women with birth outcomes 42% of infants had grossly abnormal clinical or brain
imaging findings Only 4 of 117 live-born infants had microcephaly
Source: NEJM, 12/15/2016
1/24/2017
9
Brasil P et al. N Engl J Med 2016;375:2321-2334.
Prospective Maternal Cohort and Pregnancy Outcomes
Brasil P et al. N Engl J Med 2016;375:2321-2334.
Pregnancy and Infant Outcomes According to the Week of Gestation at the Time of ZIKV Infection.
1/24/2017
10
Source: JAMA: Dec 13 2016: 317(1)
Source: JAMA: Dec 13 2016: 317(1)
Risk in
asymptomatic
women appears
same as
symptomatic
women
Risk in women
infected in 1st
trimester
appears higher
1/24/2017
11
Chen L et al. N Engl J Med 2017. DOI: 10.1056/NEJMc1610614
Cutaneous Eruption in a Pregnant Woman with Locally Acquired Zika Virus Infection.
1/24/2017
12
XxxXxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Successes
• Travel advisories issued in January kept many pregnant tourists and business travelers from venturing to areas where they might have been infected, with terrible consequences.
• The Rio Olympics was held without spreading the virus
• New diagnostic tests for Zika were developed
• Multiple vaccine candidates are showing promise
1/24/2017
13
Source: WHO Zika Situation Report, Dec 22 2016
209 million
49 million
Zika in Florida: 210 locally-acquired cases
1/24/2017
14
Zika in Texas: 6 locally-acquired cases
Reported Occurrence of Ae. aegypti by County January 1995 - March 2016-- United States
Micah B. Hahn et al. J Med Entomol 2016;53:1169-1175
Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the United States.
1/24/2017
15
Eligibility for the CDC Registry
• Pregnant women in the United States and US territories (with the exception of Puerto Rico) with laboratory evidence* of possible Zika virus infection (regardless of whether they have symptoms) and periconceptionally, prenatally, or perinatally exposed infants born to these women.
• Infants with laboratory evidence* of possible congenital Zika virus infection (regardless of whether they have symptoms) and their mothers.
1/24/2017
16
Laboratory evidence of possible Zika virus infection for the US Zika Pregnancy Registry:
• Recent Zika virus infection detected by Zika RNA nucleic acid test (NAT) (e.g., real-time reverse transcription polymerase chain reaction [rRT-PCR]): ◦Zika virus RNA detected by NAT on any maternal or fetal/infant clinical specimen (e.g., serum, urine, whole blood, cerebrospinal fluid, amniotic fluid, cord blood, saliva, placenta, umbilical cord tissue, placental membranes, or fetal tissue)
• Recent Zika virus infection or recent flavivirus infection detected by serologic tests of maternal or infant serum or cerebrospinal fluid ◦Zika virus IgM positive or equivocal AND Zika virus plaque reduction neutralization test (PRNT) titer ≥10, (regardless of dengue virus PRNT value) OR
• Zika virus IgM positive AND Zika virus PRNT not performed in following state, tribal, local, or territorial health department protocol, OR
• Zika virus IgM negative AND dengue virus IgM positive or equivocal AND Zika virus PRNT titer ≥10 (regardless of dengue virus PRNT titer)
These inclusion criteria are intentionally broad because of the known cross-reactivity in IgM testing and inability to distinguish between Zika and dengue virus through the use of PRNT.
• If maternal Zika virus IgM and dengue virus IgM are both negative, and maternal PRNT was performed per jurisdictional protocol with Zika virus PRNT titer ≥10, additional testing is needed to meet inclusion criteria. For example, if maternal testing is performed >12 weeks from possible Zika virus exposure and maternal IgM testing is negative with Zika virus PRNT titer ≥10, the mother-infant pair would be included if the infant had Zika virus IgM positive or equivocal, Zika virus RNA or antigen detected, or Zika virus cultured.
• Zika virus infection confirmed by other tests in any maternal or fetal/infant clinical specimen (e.g., serum, urine, whole blood, cerebrospinal fluid, amniotic fluid, cord blood, saliva, placenta, umbilical cord tissue, placental membranes, or fetal tissue): ◦Culture of Zika virus
• Detection of Zika virus antigen
1/24/2017
17
Questions?