Updated Interim Guidance for Health Departments on Testing and Reporting for Oropouche Virus Disease

At a glance

  • This document provides updated testing guidance for patients with suspected Oropouche virus disease, an interim case definition, and guidance for case reporting to ArboNET.
  • Updates to the guidance will be made, as needed, based on new information about Oropouche virus.

Overview

CDC can provide clinical diagnostic testing for patients meeting the suspect case definition for Oropouche virus disease. Health departments can request a consultation with CDC for an exception, including if an asymptomatic pregnant person who lived in or traveled to an area with documented or suspected Oropouche has fetal findings concerning for congenital Oropouche (e.g., microcephaly, structural brain anomalies) or experiences a stillbirth. Clinical diagnostic testing consists of CLIA-validated molecular and neutralizing antibody testing of serum or CSF. More details on the testing algorithm are described below.

Suspect case definition

A suspect case is a patient who has been in an area with documented or suspected Oropouche virus circulationA within two weeks of initial symptom onset (as patients may experience recurrent symptoms) and the following:

  • In the absence of a more likely clinical explanation, meets one of the following clinical criteria:
    • Acute onset of fever or chills or two or more of the following: headache, myalgia, arthralgia, retro-orbital pain, or generalized rash; OR
    • Meningitis, encephalitis, acute flaccid paralysis, or other acute signs of central or peripheral neurologic dysfunction, as documented by a physician.

AND

  • Tested negative for other possible diseases, in particular dengueB.

Other diagnostic considerations

In many countries, outbreaks of dengue are occurring in areas with reported Oropouche virus transmission. For patients with suspected Oropouche virus disease, it is important to rule out dengue virus infection because proper clinical management of dengue can improve health outcomes. Other diagnostic considerations include chikungunya, Zika, leptospirosis, malaria, or infections caused by various other bacterial or viral pathogens (e.g., rickettsia, group A streptococcus, rubella virus, measles virus, parvovirus, enteroviruses, adenovirus, Mayaro virus).

Specimen requirements

All specimens should be submitted to CDC through state health departments. For after-hours contact information for health departments please visit: https://www.cste.org/page/EpiOnCall.

All specimens should be submitted according to CDC's routine arboviral testing submission protocol. Please note in CSTOR or on the 50.34 Specimen Submission Form dates and results of commercial and state laboratory testing for other arboviruses, in particular dengue.

For questions about specimen requirements or submission, contact ADBClinicalTeam@cdc.gov.

Clinical diagnostic testing

For patients meeting the suspect case definition, CDC can perform CLIA-validated Oropouche virus testing using real-time reverse transcription-polymerase chain reaction (RT-PCR) to detect viral RNA and/or plaque-reduction neutralization test (PRNT) to detect neutralizing antibodies on serum and/or CSF specimens.

Clinical diagnostic test results will be sent to public health partners in the jurisdictional health department where the case resides. These results can be shared with the treating physician and can be used for clinical decision making.

Oropouche virus disease clinical diagnostic testing algorithm

The specific assay(s) used will depend on timing of specimen collection in relation to initial symptom onset in most patientsCas follows:

Day of specimen collection post symptom onset Assay
0–7 RT-PCR
6–7 PRNT, if RT-PCR is negative
>7 PRNT

Based on current knowledge of Oropouche virus disease epidemiology, if a patient meets the suspect case definition, a single PRNT result is generally considered adequate to diagnose Oropouche virus disease. However, if a specimen collected from a pregnant person is positive by PRNT only, acute and convalescent serum specimens collected optimally ≥2 weeks apart are preferred to confirm a recent infection by demonstrating a ≥4-fold change in neutralizing antibody titers. Specimens collected during the first two weeks of illness are considered acute.

Infant testing guidance is provided in Interim Guidance for Evaluating and Managing Infants Born to Pregnant People with Confirmed or Probable Oropouche Virus Disease.

Reporting cases to ArboNET

Oropouche virus disease is not currently a nationally notifiable condition. However, CDC encourages voluntary reporting to ArboNET, the national arboviral surveillance system. CDC has incorporated two new condition (event) codes for reporting:

  • 50290: Oropouche virus disease, non-congenital
  • 50291: Oropouche virus disease, congenital

For jurisdictions entering data directly into ArboNET via web or XML: These codes are already available for use. If you utilize the ArboNET Desktop Application for XML and need the latest version, please email us at dvbid2@cdc.gov.

For jurisdictions onboarded to the Arboviral MMG: CDC is aware that jurisdictions will need a transition period to modify their systems to transmit these new codes. While transitioning, CDC encourages jurisdictions to continue using condition code 10072 (Other arboviral disease, not otherwise specified) and 'Oropouche' for arbovirus. If you cannot report the arbovirus variable as 'Oropouche' then please report as 'Other Arbovirus'.

The interim case definition below should be used for classification of non-congenital Oropouche virus disease cases. CDC is working on establishing an interim case definition for congenital Oropouche virus disease. Once established, CDC will notify jurisdictional partners and update this page. For questions or further guidance on reporting, please contact dvbid2@cdc.gov.

Interim case definitions for non-congenital and congenital disease

Current testing is limited to the assays described above. However, the interim case definitions incorporate additional assays and testing on specimen types that may become available in the future.

Epidemiologic linkage

  • Resided in or traveled to an area with a riskDof Oropouche virus transmission in the 14 days before the initial onset of symptoms, in the 28 days before onset of Guillain-Barré syndrome, or during pregnancy; OR
  • Sexual contact, within 14 days of symptom onset or during pregnancy, with a person who has been diagnosed with Oropouche virus infection or has been in an area with a risk of Oropouche virus transmission (Visit Oropouche Virus and Possible Sexual Transmission for current information on Oropouche sexual transmission risk); OR
  • Laboratory exposure to Oropouche virus before onset of symptoms or during pregnancy; OR
  • Receipt of blood products, solid organs, or human cellular or tissue-based products within 30 days of symptom onset or during pregnancy from a person who has either been diagnosed with Oropouche virus infection or has been in an area with a risk of Oropouche virus transmissionE.

Oropouche virus disease, non-congenital

Clinical criteria

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

  • Acute onset of fever or chills or two or more of the following: headache, myalgia, arthralgia, retroorbital/eye pain, or generalized rash; OR
  • Meningitis, encephalitis, acute flaccid paralysis, or other acute signs of central or peripheral neurologic dysfunction, as documented by a physician; OR
  • Loss of a fetus at greater than or equal to 20 weeks gestation.

Laboratory Criteria

  • Confirmatory laboratory evidence:
    • Detection of Oropouche virus, viral antigen, or viral RNA in a body fluid or tissue; OR
    • Four-fold or greater change in Oropouche virus-specific quantitative antibody titers in paired sera; OR
    • Detection of Oropouche virus-specific IgM antibodies in blood or CSF with confirmatory virus-specific neutralizing antibodies in the same or a later specimen.
  • Presumptive laboratory evidence:
    Detection of Oropouche virus-specific IgM or neutralizing antibodies in blood or CSF.

Case classification

Confirmed non-congenital disease case
Meets the epidemiologic linkage criteria and clinical and confirmatory laboratory criteria for non-congenital Oropouche virus disease.

Probable non-congenital disease case
Meets the epidemiologic linkage criteria and clinical and presumptive laboratory criteria for non-congenital Oropouche virus disease.

Oropouche virus disease, congenital

Clinical criteria

  • To meet the clinical criteria for congenital Oropouche virus disease, the liveborn infant must not have an identified genetic or other cause for the findings, including a positive test for another likely etiologyF, and should have 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 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).

Laboratory criteria

  • Confirmatory laboratory evidence:
    • Detection of Oropouche virus, viral antigen, or viral RNA in the infant’s body fluid or tissueG; OR
    • Detection of Oropouche virus-specific IgM antibodies in infant CSF or bloodG, with positive Oropouche virus-specific neutralizing antibody titers.
  • Presumptive laboratory evidence:
    • Detection of Oropouche virus, viral antigen, or viral RNA in amniotic fluid, placenta, umbilical cord, or cord blood; OR
    • Detection of Oropouche virus-specific IgM antibodies in infant blood or CSFG.

Case Classification

Confirmed congenital disease case

  • Meets the clinical criteria for congenital Oropouche virus disease, AND
  • Meets the confirmatory laboratory criteria for congenital Oropouche virus disease, AND
  • Whose gestational parent meets:
    • Epidemiologic linkage criteria, OR
    • Confirmatory or presumptive laboratory criteria for non-congenital Oropouche virus disease during this pregnancy.

Probable congenital disease case

  • Meets the clinical criteria for congenital Oropouche virus disease, AND
  • Meets the presumptive laboratory criteria for congenital Oropouche virus disease, AND
  • Whose gestational parent meets:
    • Epidemiologic linkage criteria, OR
    • Confirmatory or presumptive laboratory criteria for non-congenital Oropouche virus disease during this pregnancy.

Suspect congenital disease case

  • Meets the clinical criteria for congenital Oropouche virus disease, AND
  • 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
  • Whose gestational parent meets confirmatory or presumptive laboratory criteria for non-congenital Oropouche virus disease during this pregnancy.
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Content Source:
National Center for Emerging and Zoonotic Infectious Diseases
  1. If concern exists for local transmission in a non-endemic area, consider if the patient shared an exposure location with a person with confirmed Oropouche virus infection, lives in an area where travel-related cases have been identified, or has known vector exposure (e.g., mosquitoes or biting midges).
  2. If strong suspicion of Oropouche virus disease exists based on the patient's clinical features, history of travel to an area with virus circulation, or other potential exposures, testing for Oropouche can be requested before other testing is completed.
  3. If a patient is immunocompromised from an underlying illness or medication or has another condition that might impact their immune response, RT-PCR can be conducted on samples collected after the first week of illness. Please indicate if a patient is considered immunocompromised in CSTOR or on the 50.34 Specimen Submission Form
  4. Consult with CDC as needed for assistance with geographic risk determinations.
  5. Contact CDC for further guidance given limited data on these potential modes of transmission.
  6. 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.
  7. To prevent misclassifying postnatal Oropouche virus disease as congenital cases, in Oropouche virus endemic areas specimens should be collected within 4 weeks after birth.