- amniotic fluid analysis
- Centers for Disease Control and Prevention recommendations
- counseling of the patient at risk
- Dengue virus
- fetal magnetic resonance imaging
- Food and Drug Administration regulations
- head circumference
- flaviviridae family
- immunoglobulin M serology
- perinatal viral infection
- plaque reduction neutralization test
- reverse transcriptase–polymerase chain reaction
- transplacental transmission of viruses
- viral culture
- viral detection with polymerase chain reaction
- viral detection with real-time reverse transcriptase–polymerase chain reaction
- Zika virus
- Zika virus in pregnancy
Epidemiology and estimates of congenital ZIKV infection
Who should be tested and how?
Why should we test and not just screen for microcephaly with ultrasound? Molecular diagnostics for viral pathogens and estimation of risk
Currently available laboratory-based testing for ZIKV
|Test category||Specimen sources||Timing of first positive test|
|Duration of positive test|
|Limitations||Interpretations of positive tests|
|4 d in symptomatic|
7-14 d in asymptomatic
|PRNT||Serum||With positive serological testing||See Table 2|
|Viral nucleic acid testing||rRT-PCR||Serum|
|Recent Zika infection|
|Variable||Once present, appears progressive||When performed in isolation, cannot distinguish anomaly cause. When performed in conjunction with amniocentesis with chromosomal microarray or other infectious pathogen testing, improved specificity; see Table 3.|
|IgM ELISA testing||Result||Interpretation|
|ZIKV IgM||Detected||No evidence of Zika or Dengue infection, false-positive IgM|
|ZIKV PRNT||Not detected|
|DENV PRNT||Not detected|
|ZIKV IgM||Positive or equivocal||Recent Zika virus infection|
|DENV IgM||Positive or equivocal|
|ZIKV IgM||Positive or equivocal||Recent Dengue virus infection|
|DENV IgM||Positive or equivocal|
|ZIKV IgM||Inconclusive in one assay and inconclusive or negative in the other||Recent flavivirus infection; specific virus cannot be determined|
|ZIKV IgM||Inconclusive in one assay and inconclusive or negative in the other||Evidence of Zika virus; timing cannot be determined|
|ZIKV IgM||Inconclusive in one assay and inconclusive or negative in the other||Evidence of Dengue virus; timing cannot be determined|
|ZIKV IgM||Inconclusive in one assay and inconclusive or negative in the other||Evidence of flavivirus infection; specific virus and timing of infection cannot be determined|
Ultrasound-based fetal assessment
|Ultrasound view||Abnormality||Specificity for congenital ZIKV infection|
|Transventricular (axial view)|
|Transthalamic (axial view)|
|Transcerebellar (coronal and axial views)|
|Midsagittal plane (sagittal view)|
|Transcaudate (coronal view)|
|Brain parenchyma and cortex (can be assessed in all views)|
|Amniotic fluid assessment|
Fetal brain imaging in cases of suspected congenital ZIKV infection
How do we counsel women with laboratory-based evidence of recent ZIKV infection?
Knowing what we do not know and prioritizing what we need to learn
Future prevention and interventions
Zika Virus Vaccines. Available at: https://www.niaid.nih.gov/diseases-conditions/zika-vaccines. Accessed Dec. 30, 2016.
- Avidity: the overall binding strength between an antibody and an antigen, which is reflective of both the affinity of the antibody for its epitope and the antibody valency. In general, avidity testing is done with IgG isotype antibodies and lower avidity is seen with more recent infection.
- Arbovirus: viruses transmitted by arthropod (including mosquitoes) vectors.
- Dengue virus (DENV): DENV is the causative virus of dengue fever. Like ZIKV and DENV, CHIKV is a positive-stranded RNA arbovirus of the Flaviviridae family, genus Flavivirus. Unlike ZIKV, despite well-documented exposures in pregnancy, DENV does not cause congenital malformations.
- Chikungunya virus (CHIKV): CHIKV is the causative virus of chikungunya. Like ZIKV, DENV is a positive-stranded RNA arbovirus of the Togaviridae family, genus alphavirus. It too is transmitted by the same Aedes spp. of mosquitos and, similar to both ZIKV and DENV infection, causes mild to severe symptoms of fever, rash, arthralgia, and headache. However, unlike ZIKV, it is not known to cause congenital malformations.
- Flaviviridae family: the family of viruses to which both DENV and ZIKV belong. Humans and other mammals serve as their natural hosts, and they are transmitted primarily through arthropod vectors such as mosquitos and ticks. Other members of the family include yellow fever virus, West Nile virus, and St Louis encephalitis virus (all of the genus Flavivirus) as well as hepatitis C (genus Hepacivirus).
- Microcephaly: acute or chronic slowing in head growth, resulting in a small head circumference relative to gestational age and body size, strictly defined as measuring greater than 3 SD (or Z scores) below the standardized population mean. There are multiple causes of microcephaly, including congenital infections (such as ZIKV, cytomegalovirus, toxoplasmosis, rubella and herpes virus, syphilis, and HIV), chromosomal abnormalities (including both aneuploidy and structural malformations, such as Down syndrome and microdeletion syndromes), exposure to toxic environmental pollutants and teratogens (such as arsenic and mercury, alcohol, and radiation), and acute trauma with hypoxic-ischemic injury. During the course of the current ZIKV pandemic, different organizations and publications have used a working definition of microcephaly of both –2 and –3 SD to define microcephaly.
- Nucleic acid test: a generalized term referring to a nucleic acid test (NAT) or nucleic acid amplification test (NAAT), which are molecular-based approaches for detecting and quantifying a particular pathogen (virus or bacterium) in a specimen of blood or other tissue or body fluid.
- Pandemic: an infectious epidemic that has documented spread across a large region, generally spanning continents.
- Plaque reduction neutralization test (PRNT): quantification of the titer of neutralizing antibody for a virus. Values are provided as fold higher or lower titers by PRNT.
- rRT-PCR (real-time reverse transcriptase–polymerase chain reaction): the NAT methodology used currently for ZIKV, rRT-PCR quantitatively monitors the amplification of ZIKV nucleic acid through the creation of complementary transcripts during the PCR (i.e., in real time).
- Zika virus (ZIKV): the causative viral pathogen of Zika disease and congenital Zika syndrome.
Glossary of Terms
- Supplementary Data
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This study was supported by the National Institutes of Health (grant NR014792 to K.M.A.; grant K99HD075858 to M.A.S.), the March of Dimes Prematurity Research Initiative (to KMA), and Baylor College of Medicine/Texas Children’s Hospital (to K.M.A., M.A.S., and M.A.B.).
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