Criteria

Centers for Disease Control and Prevention (CDC): Zika virus disease case definition - congenital Zika virus disease

The CDC have separate case definitions for congenital disease and noncongenital disease (see below).[189]

Clinical criteria

  • To meet the clinical criteria for congenital Zika virus disease, the liveborn infant must not have an identified genetic or other cause for the findings, including a positive test for another likely etiology, and should have one or more of the following brain or eye anomalies or neurologic sequelae specific for congenital Zika virus disease and typically identifiable in the neonatal period:

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

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

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

    • Intracranial calcifications (most commonly between the cortex and subcortex)

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

    • Congenital paralysis of the diaphragm associated with structural brain anomalies

    • Corpus callosum agenesis/hypoplasia

    • Cerebellar hypoplasia

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

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

  • Clinical findings can be observed during the prenatal or postnatal evaluations.

Laboratory criteria

  • Confirmatory laboratory evidence:

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

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

  • Presumptive laboratory evidence:

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

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

Case classification

  • Probable:

    • Meets the clinical criteria for congenital Zika virus disease; AND

    • Meets presumptive laboratory criteria for congenital Zika virus disease; AND

    • Whose gestational parent meets: epidemiologic linkage criteria; OR confirmatory laboratory criteria for noncongenital Zika virus disease during the pregnancy.

  • Confirmed:

    • Meets the clinical criteria for congenital Zika virus disease; AND

    • Meets confirmatory laboratory criteria for congenital Zika virus disease; AND

    • Whose gestational parent meets: epidemiologic linkage criteria: OR confirmatory laboratory criteria for noncongenital Zika virus disease during the pregnancy.

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Centers for Disease Control and Prevention: Zika virus disease case definition - noncongenital Zika virus disease

The CDC have separate case definitions for noncongenital disease and congenital disease (see above).[189]

Clinical criteria

  • To meet the clinical criteria for noncongenital Zika virus disease, the person should have one or more of the following not explained by another etiology:

    • Acute onset of one or more of the following symptoms: fever (measured or reported); generalized rash; arthralgia; or nonpurulent conjunctivitis

    • Guillain-Barre syndrome

    • Loss of a fetus at ≥20 weeks gestation.

Laboratory criteria

  • Confirmatory laboratory evidence:

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

    • 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.

  • Presumptive laboratory evidence:

    • 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; OR

    • Fourfold or greater rise in anti-Zika virus-specific neutralizing antibody titers in paired blood specimens; OR

    • 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.

Case classification

  • Probable:

    • Meets the epidemiologic linkage criteria, and clinical and presumptive laboratory criteria for noncongenital Zika virus disease.

  • Confirmed:

    • Meets the epidemiologic linkage criteria, and clinical and confirmatory laboratory criteria for noncongenital Zika virus disease.

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World Health Organization (WHO): interim case definition

An interim case definition has been published by the WHO for the purpose of global standardization of classification and reporting.​[170]

Suspected case:

  • A person presenting with rash and/or fever and at least one of the following signs or symptoms:

    • Arthralgia

    • Arthritis

    • Conjunctivitis (nonpurulent/hyperemic).

Probable case:

  • A suspected case with the presence of IgM antibodies against Zika virus and no evidence of infection with other flaviviruses, plus an epidemiologic link (i.e., contact with a confirmed case, or a history of residence in or traveling to an area with local transmission of Zika virus within 2 weeks prior to onset of symptoms).

Confirmed case:

  • A person with laboratory confirmation of recent Zika virus infection:

    • Presence of Zika virus RNA or antigen in serum or other samples (e.g., saliva, tissues, urine, whole blood)

    • IgM antibody against Zika virus is positive and plaque reduction neutralization test (PRNT) for Zika virus with titer ≥20 and Zika virus PRNT titer ratio ≥4 compared with other flaviviruses.

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Pan American Health Organization (PAHO): interim Zika virus case definition

An interim case definition has been published by the PAHO.[144]

Suspected case:

  • Patient with rash (usually pruritic and maculopapular) plus 2 or more of the following:

    • Fever (usually <101.3°F [<38.5°C])

    • Conjunctivitis (nonpurulent/hyperemic)

    • Arthralgia

    • Myalgia

    • Periarticular edema

  • In geographic areas without autochthonous transmission and where there are no vectors present, patients who meet the criteria above and who:

    • in the 2 weeks prior to onset, traveled to/resided in a geographic area where there is known local transmission of the Zika virus or there is known vector presence; or

    • had unprotected sex in the 2 weeks prior to onset with a person who traveled in the previous 8 weeks to a geographic area with known local transmission of the Zika virus or an area with known vector presence.

Probable case:

  • Patient who meets the criteria of a suspected case and has Zika IgM antibodies with no evidence of infection with other flaviviruses.

Confirmed case:

  • Patient who meets the criteria of a suspected case and has laboratory confirmation of recent Zika virus infection:

    • RNA or Zika virus antigen in any specimen (i.e., serum, urine, saliva, tissue, or whole blood); or

    • Positive Zika IgM antibodies and PRNT for Zika virus titers ≥20 and 4 or more times greater than the titers for other flaviviruses, as well as exclusion of other flaviruses; or

    • Detection of viral genome (in fresh or paraffin tissue) in autopsy specimens by molecular techniques, or detection by immunochemistry.

PAHO have also published case definitions for Guillain-Barre syndrome or a congenital syndrome associated with Zika virus, as well as definitions for Zika virus-associated abortion or still birth and vertical transmission (without congenital syndrome).

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