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

Overview

CDC currently offers both surveillance and clinical diagnostic testing for patients meeting the suspect case definition for Oropouche. Surveillance testing consists of non-CLIA validated tests. Because the assays are not clinically validated, surveillance testing results can be used for surveillance purposes only, and CDC will not be providing results to patients, clinicians, or otherwise for clinical decision making. Surveillance testing for Oropouche virus currently includes molecular testing. Clinical diagnostic testing consists of CLIA-validated neutralizing antibody testing of serum or CSF. More details on both testing options are provided in the sections below.

Suspect case definition

Patient with travel within two weeks of initial symptom onset (as patients may experience recurrent symptoms) to an area with documented or suspected Oropouche virus circulation* and the following:

• Abrupt onset of reported fever, headache, and one or more of the following: myalgia, arthralgia, photophobia, retroorbital/eye pain, or signs and symptoms of neuroinvasive disease (e.g., stiff neck, altered mental status, seizures, limb weakness, or cerebrospinal fluid pleocytosis); AND
• No respiratory symptoms (e.g., cough, rhinorrhea, shortness of breath); AND
• Tested negative for other possible diseases, in particular dengue†.

*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).

†If strong suspicion of Oropouche virus disease exists based on the patient's clinical features and history of travel to an area with virus circulation, do not wait on negative testing before sending specimens to CDC.

Specimen requirements

For serum or CSF collected within the first 10 days of illness, a minimum of 1.0 ml is preferred as this will allow for both Oropouche virus clinical diagnostic and surveillance testing (for volumes <0.5 ml contact ADBClinicalTeam@cdc.gov for guidance).

• 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.

The local jurisdiction should split the specimen before sending to CDC. This approach to splitting of specimens will be used until a CLIA-validated PCR assay is available at CDC. Revised guidance for use of the CLIA-validated PCR assay will be released on this website at that time.

• One half should be submitted for clinical diagnostic testing according to CDC's routine arboviral testing submission protocol.
• The other half should be submitted for surveillance testing using an anonymous local specimen ID and must not include the patient demographic or clinicians' details. Surveillance specimens should be sent using the same shipping instructions (i.e., temperature, packaging, etc.) as for other arboviral diagnostic specimens.

For serum or CSF collected after the first 10 days of illness, a minimum of 0.5 ml is preferred to allow for Oropouche virus serologic testing and any other necessary testing for other circulating arboviruses (for volumes <0.5 ml contact ADBClinicalTeam@cdc.gov for guidance).

• Since the convalescent specimen will only be tested for antibodies using the clinical diagnostic test, it should be submitted according to CDC's routine arboviral testing submission protocol. Please note on the 50.34 Specimen Submission Form dates and results of commercial and state laboratory testing for other arboviruses, in particular dengue.

Submitting for surveillance testing

Specimens for surveillance testing should be shipped to:

CDC-DVBD

ATTN: Virology Team (Aaron Brault, Holly Hughes)

3156 Rampart Road

Fort Collins, CO 80521

In advance of sending specimens for surveillance testing, please notify the Arboviral Diseases Branch clinical team at ADBClinicalTeam@cdc.gov. Please email the following information in advance of sending specimens for surveillance testing (see Excel spreadsheet template):

• ID number (no link to patient identifiers can be provided to CDC)
• State of residence
• Symptom onset date (please include date of onset of initial symptoms if patient experienced a recurrence).
• Symptoms (please list all known symptoms associated with this illness. If patient experienced a recurrence, please list date of initial symptom resolution and date of recurrence).
• Immunocompromising conditions or medications
• Travel location(s)
• Travel dates
• Specimen type(s)
• Specimen collection date(s)
• Dates and results of commercial and state laboratory testing for other arboviruses, in particular dengue

Clinical diagnostic testing

Patients meeting the suspect case definition should have clinical diagnostic testing, if possible. At this time, clinical diagnostic testing at CDC can only be completed on serum or CSF using a CLIA-validated plaque reduction neutralization test (PRNT). To confirm a recent infection in a patient, paired specimens are needed to demonstrate a 4-fold or greater change in Oropouche virus-specific quantitative neutralizing antibody titers between acute- and convalescent-phase serum specimens collected optimally ≥2 weeks apart. If paired specimens cannot be obtained, detection of neutralizing antibodies in a single specimen is considered laboratory evidence of infection, but since timing cannot be determined, clinical correlation is needed for interpretation.

Given the evidence indicating a risk of vertical transmission of Oropouche virus from a gestational parent to their fetus, paired acute and convalescent specimens collected optimally ≥2 weeks apart are needed to confirm recent infection in a pregnant person.

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.

Clinical diagnostic testing algorithm

• Clinical diagnostic testing should be considered for patients meeting the suspect case definition.
• Paired acute and convalescent serum and/or CSF specimens should optimally be collected ≥2 weeks apart.
  • At this time, antibody kinetics have not been well defined for Oropouche virus infections. Until more is known, CDC recommends collecting acute and convalescent samples.
  • Samples obtained during the initial illness phase (e.g., when the patient presents with their first symptoms) are considered acute. Samples obtained after recovery from the initial illness, including during the recurrence of symptoms, are considered convalescent samples.
• PRNT will be run on paired specimens in parallel to allow for detection of a 4-fold or greater change in neutralizing antibody titers.
  • A 4-fold change in 90% plaque reduction neutralizing antibody titers (PRNT₉₀) is considered confirmatory laboratory evidence of recent infection.
• If paired specimens cannot be obtained, a single specimen will be tested using PRNT.
  • A PRNT₉₀ titer of ≥10 is considered laboratory evidence of infection, but since timing of infection cannot be determined, clinical correlation is needed for interpretation (e.g., timing of travel and potential vector exposure in relation to symptom onset, clinical features, absence of other etiologies of symptoms).

Surveillance testing

Surveillance testing is performed to allow for the detection, response, and control of emerging and re-emerging arboviruses, such as Oropouche virus. Results of the surveillance testing will be shared with public health partners in the jurisdictional health department where the patient resides to allow for awareness and public health action. The results will have a cover letter noting a non-validated CLIA assay was used for the purpose of surveillance and are not to be shared with the patient or clinical team caring for the patient. Results will be conveyed using local sample ID only and will not include any patient or clinician identifiers.

Surveillance testing algorithm

• Oropouche virus surveillance testing should be considered for individuals meeting the suspect case definition and for whom serum and/or CSF specimens have been collected up to 10 days after symptom onset.
• Specimens will be tested in duplicate using a modified Oropouche virus real-time reverse transcription-polymerase chain reaction (rRT-PCR).

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. Jurisdictions can report cases 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 criteria below should be used for classification of Oropouche cases. For questions or further guidance on reporting, please contact dvbid2@cdc.gov.

Interim case definition

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

Confirmed case

A case that meets the suspect case definition* and one or more of the following laboratory criteria:

• Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, CSF, or other body fluid
• Four-fold or greater change in virus-specific quantitative antibody titers in paired sera
• Virus-specific IgM antibodies in CSF or serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen

Probable case

A case that meets the suspect case definition* and one of the following laboratory criteria:

• Virus-specific IgM antibodies in CSF or serum
• Virus-specific neutralizing antibodies in a single CSF or serum specimen

*Absence of a more likely clinical explanation.