Non-congenital Zika Virus Disease

2023 Case Definition

CSTE Position Statement Number: 23-ID-10 

Clinical Presentation

Most people infected with Zika virus have asymptomatic infections or mild clinical disease characterized by acute onset of fever, maculopapular rash, arthralgia, and nonpurulent conjunctivitis. Other common symptoms can include myalgia, headache, edema, vomiting, retroorbital pain, or lymphadenopathy.

Clinical Criteria

To meet the clinical criteria for non-congenital Zika virus disease, the person should have one or more of the following not explained by another etiology.

Laboratory Criteria

 

Confirmatory laboratory evidence:

 

Presumptive laboratory evidence:

Epidemiologic Linkage

Case Classification

Confirmed:

Probable:

 

Criteria to Distinguish a New Case of Zika virus disease from Reports or Notifications which Should Not be Enumerated as a New Case for Surveillance

Classification Table: Criteria for Defining a Case of Non-congenital Zika Virus Disease

Criterion

Non-congenital Zika virus disease

Congenital Zika virus disease


Confirmed

Probable

Confirmed

Probable

Clinical Evidence









Acute onset of one or more of the following symptoms:

O

O







  • Fever (measured or reported)

  • Generalized rash

  • Arthralgia

  • Non-purulent conjunctivitis

Guillain-Barré syndrome

O

O







Loss of a fetus at ≥20 weeks gestation

O

O







Clinical evidence not explained by another etiology

N

N







Liveborn infant



N

N

N

N

N

N

No identified genetic or other cause for the findings, including a positive test for another likely etiology^



N

N

N

N

N

N

Microcephaly (occipital frontal circumference >2 standard deviations below the mean for age and sex) at birth or postnatal onset



O

O

O

O

O

O

Cortical hypoplasia or abnormal gyral patterns (polymicrogyria, lissencephaly, heterotopia)



O

O

O

O

O

O

Increased volume of cerebrospinal fluid (CSF) (hydrocephalus ex vacuo, unspecified hydrocephalus, ventriculomegaly) due to loss of brain parenchyma



O

O

O

O

O

O

Intracranial calcifications (most commonly between the cortex and subcortex)



O

O

O

O

O

O

Congenital contractures of major joints (arthrogryposis) associated with structural brain anomalies



O

O

O

O

O

O

Congenital paralysis of the diaphragm associated with structural brain anomalies



O

O

O

O

O

O

Corpus callosum agenesis/hypoplasia



O

O

O

O

O

O

Cerebellar hypoplasia



O

O

O

O

O

O

Scarring of the macula with coarse deposits of pigment in the retina (focal retinal pigmentary mottling)



O

O

O

O

O

O

Other structural eye anomalies (microphthalmia, cataracts, chorioretinal atrophy, optic nerve hypoplasia)



O

O

O

O

O

O

Laboratory Evidence









Detection of Zika virus, viral antigen, or viral RNA in a body fluid or tissue

O



N#



N#


Detection of anti-Zika virus IgM antibodies in blood or CSF, with positive Zika virus-specific neutralizing antibody titers and negative neutralizing antibody titers against dengue or other flaviviruses endemic to the region where exposure occurred

O




N#



N#

Detection of anti-Zika virus IgM antibodies in blood or CSF with a negative anti-dengue virus IgM antibody test in the same specimen with no neutralizing antibody testing performed


O







Four-fold or greater rise in anti-Zika virus-specific neutralizing antibody titers in paired blood specimens


O







In the setting of a Zika virus outbreak** with minimal circulation of other endemic flaviviruses, detection of anti-Zika virus IgM antibodies in blood or CSF


O







Detection of Zika virus, viral antigen, or viral RNA in infant CSF, blood, urine, or postmortem tissue***



O

O

O





Detection of anti-Zika virus IgM antibodies in infant CSF or blood***, with positive anti-Zika virus-specific neutralizing antibody titers



O

O

O




Detection of Zika virus, viral antigen, or viral RNA in amniotic fluid, placenta, umbilical cord, or cord blood***






O

O

O

Detection of anti-Zika virus IgM antibodies in infant CSF or blood*** with no neutralizing antibody testing performed






O

O

O

Epidemiologic Linkage Evidence









Resided in or traveled to an area with a risk** of Zika virus transmission in the 14 days before the onset of symptoms or in the 28 days before the onset of Guillain-Barré syndrome

O

O







Laboratory exposure to Zika virus before onset of symptoms

O

O







Receipt of blood, blood products, organ transplant, or tissue transplant within 30 days of symptom onset from a person who has either been diagnosed with Zika virus infection or returned from traveling to an area with risk** of Zika virus transmission

O

O







Sexual contact, within 14 days of symptom onset, with a person who in the last 90 days has either been diagnosed with Zika virus infection or has returned from traveling to an area with a risk** of Zika virus transmission

O

O







Has a gestational parent who resided in or traveled to an area with a risk** of Zika virus transmission during pregnancy



O



O



Has a gestational parent with a laboratory exposure to Zika virus during pregnancy



O



O



Has a gestational parent who received blood, blood products, organ transplant, or tissue transplant during pregnancy from a person who has either been diagnosed with Zika virus infection or returned from traveling to an area with risk** of Zika virus transmission



O



O



Has a gestational parent who had sexual contact during pregnancy with a person who in the last 90 days has either been diagnosed with Zika virus infection or has returned from traveling to an area with a risk** of Zika virus transmission



O



O



Notes:

N = All “N” criteria in the same column are NECESSARY to classify a case.

O = At least one of these “O” (ONE OR MORE) criteria in each category (categories=clinical evidence, laboratory evidence, and epidemiologic evidence) in the same column—in conjunction with all “N” criteria in the same column—is required to classify a case.

^ Other clinical considerations for congenital Zika virus disease: Among congenital infections, cytomegalovirus infection has clinical findings most consistent with Zika virus infection and should be ruled out by diagnostic testing. While other infectious etiologies (e.g., rubella virus, varicella zoster virus, herpes simplex virus, lymphocytic choriomeningitis virus, Toxoplasma gondii, or Treponema pallidum) have clinical findings less consistent with congenital Zika virus disease, testing for these infections should be considered as part of the complete evaluation for congenital disease.

* If Zika and dengue virus IgM antibodies are detected and neutralizing antibodies are unable to differentiate flaviviruses, consider reporting as Flavivirus disease, not otherwise specified (See ArboNET Surveillance Guide).

** Consult with CDC as needed for assistance with outbreak status or geographic risk determinations.

*** To prevent misclassifying postnatal Zika virus infections as congenital cases, in Zika virus endemic areas specimens should be collected within 4 weeks after birth.

Classification Table: Criteria to distinguish a new case of non-congenital and congenital Zika virus disease from reports or notifications which should not be enumerated as a new case for surveillance.

Criterion

Non-Congenital Zika virus disease

Congenital Zika virus disease


Confirmed

Probable

Confirmed

Probable

Criteria to distinguish a new case

A person not previously enumerated as a case that meets the confirmed or probable case classification

S

S

S

S

S = This criterion alone is SUFFICIENT to enumerate as a new case.


[1] If Zika and dengue virus IgM antibodies are detected and neutralizing antibodies are unable to differentiate flaviviruses, consider reporting as Flavivirus disease, not otherwise specified

[2] Consult with CDC as needed for assistance with outbreak status determinations.

[3] Consult with CDC as needed for assistance with geographic risk determinations.