Non-congenital Oropouche Virus Disease
2025 Case Definition

Clinical Criteria

A liveborn infant without an identified genetic or other cause for the findings, including a positive test for another likely etiology^§, and one or more of the following congenital anomalies typically identifiable in the neonatal period:

• Microcephaly (defined as head circumference measurement >2 standard deviations below the average [or <3rd percentile] for the same age and sex, notation of microcephaly in the medical record, or diagnostic
  code of microcephaly [e.g., ICD-10 code Q02]), OR
• Structural brain anomalies (e.g., ventriculomegaly, cortical hypoplasia, abnormal gyral patterns such as lissencephaly, corpus callosum abnormalities), OR
• Structural eye anomalies (e.g., microphthalmia, chorioretinal atrophy, optic nerve hypoplasia), OR
• Congenital contractures of major joints (arthrogryposis).

^§ Other infectious etiologies (e.g., Zika virus, cytomegalovirus, rubella virus, varicella zoster virus, herpes simplex virus, lymphocytic choriomeningitis virus, Toxoplasma gondii, or Treponema pallidum) may have similar clinical findings, and testing for these infections should be considered as part of the complete evaluation for congenital disease.

Laboratory Criteria

Confirmatory Laboratory Evidence:^¶

• Detection of Oropouche virus, viral antigen, or viral RNA in the infant’s body fluid or tissue, OR
• Detection of OROV-specific IgM antibodies in infant blood or CSF with positive OROV-specific neutralizing antibody titers.

Presumptive Laboratory Evidence:^¶

• Detection of Oropouche virus, viral antigen, or viral RNA in mother’s amniotic fluid, placenta, umbilical cord, or cord blood^#, OR
• Detection of OROV-specific IgM antibodies in infant blood or CSF.

^¶ To prevent misclassifying postnatal OROV disease as congenital cases, in OROV endemic areas specimens should be collected within 4 weeks after birth.

^# Positive laboratory findings in amniotic fluid, placenta, umbilical cord, or cord blood are considered presumptive evidence of congenital OROV disease since they may detect infection in the mother in the absence of congenital infection.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.

Suspect

• Infant meets the clinical criteria for congenital OROV disease, AND
• Infant has no laboratory testing performed or in the absence of IgM testing, has no detection of Oropouche virus, viral antigen, or viral RNA in any specimen, AND
• Infant whose mother meets confirmatory or presumptive laboratory criteria for non-congenital OROV disease during this pregnancy.

Probable

• Infant meets the clinical criteria for congenital OROV disease, AND
• Infant meets the presumptive laboratory criteria for congenital OROV disease, AND
• Infant whose mother meets:
  • Epidemiologic linkage criteria, OR
  • Confirmatory or presumptive laboratory criteria for non-congenital OROV disease during this pregnancy.

Confirmed

• Infant meets the clinical criteria for congenital OROV disease, AND
• Infant meets the confirmatory laboratory criteria for congenital OROV disease, AND
• Infant whose mother meets:
  • Epidemiologic linkage criteria, OR
  • Confirmatory or presumptive laboratory criteria for non-congenital OROV disease during this pregnancy.

Background

Oropouche virus (OROV) is an emerging virus in the Americas endemic to the Amazon basin.¹ The virus is spread to people by infected biting midges and possibly some mosquito species. In 2024, OROV caused outbreaks in South America and the Caribbean, expanding into areas to which the virus was previously not endemic.² This geographic range expansion, in conjunction with reports of fatalities and vertical transmission potentially associated with fetal deaths and birth defects, has raised concerns about the broader threat this virus represents to the Americas.³ In 2024, cases were identified in the United States, Canada, and Europe associated with travel to Cuba or Brazil.^4-6 A standardized case definition has been established to facilitate national notification, enabling effective monitoring and detection of OROV risk factors, adverse outcomes, outbreaks, and transmission mechanisms, thereby informing control and prevention measures.

Epidemiologic Linkage

• Resided in or traveled to an area with a risk* of OROV transmission in the 14 days before symptom onset, in the 28 days before onset of Guillain-Barré syndrome, or during pregnancy, OR
• Sexual contact, in the 14 days before symptom onset or during pregnancy, with a person who has recently been diagnosed with OROV infection or has recently been in an area with a risk* of OROV transmission^†, OR
• Laboratory exposure to OROV before onset of symptoms or during pregnancy, OR
• Receipt of blood products, solid organs, or human cellular or tissue-based products in the 30 days before symptom onset or during pregnancy from a person who has either been diagnosed with OROV infection or has been in an area with a risk* of OROV transmission.^‡

* Visit countries and territories at risk for Oropouche for geographic areas with known current or previous risk of OROV, for areas where cases have not been previously identified, consult with CDC for assistance on risk determination.

^† Visit possible sexual transmission for current information on Oropouche sexual transmission risk.

^‡ Contact CDC for further guidance given limited data on these potential modes of transmission.

Criteria to Distinguish a New Case from an Existing Case

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

Comments

The 2025 interim case definition for non-congenital and congenital Oropouche virus disease is effective for implementation starting March 7, 2025.