The Centers for Disease Control and Prevention (CDC) is issuing this Health Advisory to inform healthcare professionals and public health authorities of the rising incidence of Oropouche virus disease in the Americas, with origins in endemic zones within the Amazon basin, and now spreading to new territories in South America and the Caribbean. From January 1 to August 1, 2024, over 8,000 cases of Oropouche virus disease have been documented, including two fatalities and five instances of vertical transmission leading to fetal death or congenital defects. Nations reporting cases include Brazil, Bolivia, Peru, Colombia, and Cuba. Travel-related cases have also been detected in the United States and Europe, primarily among travelers returning from Cuba and Brazil. As Oropouche virus testing and surveillance increase throughout the Americas, it is anticipated that additional countries will report cases. This advisory provides guidance for evaluating and testing travelers from affected regions who exhibit symptoms consistent with Oropouche virus infection. It also underscores the potential risk of vertical transmission during pregnancy and associated adverse outcomes, while highlighting preventive measures to curb the spread of the virus and avert its introduction into unaffected regions, including the United States.

Background
Oropouche virus is part of the Simbu serogroup within the Orthobunyavirus genus, Peribunyaviridae family. First identified in 1955 in Trinidad and Tobago, the virus is endemic to the Amazon basin. Previous outbreaks have occurred in Bolivia, Brazil, Colombia, Ecuador, French Guiana, Panama, and Peru. A singular case was reported in Haiti in 2014. The ongoing outbreak in 2024 is affecting both endemic and new regions outside the Amazon basin, with locally acquired cases now recorded in Brazil, Bolivia, Peru, Colombia, and Cuba. Although travel-related cases have surfaced in the United States, no evidence of local transmission has been observed within U.S. territories.

Sylvatic enzootic transmission of Oropouche virus takes place in forested areas through interactions between mosquitoes and non-human vertebrate hosts such as sloths, non-human primates, domestic and wild birds, and rodents. Humans can contract the virus while visiting forested areas, likely introducing it into urban settings. Infected individuals can serve as amplifying hosts due to sufficient viremia levels, facilitating transmission in urban environments through biting midges (Culicoides paraensis) and potentially certain mosquito species (Culex quinquefasciatus).

Approximately 60% of individuals infected with Oropouche virus develop symptoms. The incubation period typically ranges from 3 to 10 days. Initial clinical presentations resemble those of diseases caused by dengue, Zika, and chikungunya viruses, with acute onset of fever, chills, headache, myalgia, and arthralgia. Other symptoms may include retro-orbital eye pain, photophobia, nausea, vomiting, diarrhea, fatigue, maculopapular rash, conjunctival injection, and abdominal pain. Clinical laboratory findings may show lymphopenia, leukopenia, elevated C-reactive protein (CRP), and slightly elevated liver enzymes. Initial symptoms generally subside after a few days, but around 70% of patients experience recurrent symptoms days to weeks after initial recovery. While the disease is typically mild, an estimated 5% of patients may develop hemorrhagic manifestations (e.g., epistaxis, gingival bleeding, melena, menorrhagia, petechiae) or neuroinvasive disease (e.g., meningitis, meningoencephalitis). Neuroinvasive disease symptoms may include severe occipital pain, dizziness, confusion, lethargy, photophobia, nausea, vomiting, nuchal rigidity, and nystagmus. Clinical laboratory findings for neuroinvasive cases include pleocytosis and elevated protein in cerebrospinal fluid (CSF).

Individuals at greater risk for severe Oropouche virus disease are not well-defined, though risk factors likely mirror those for severe disease from other vector-borne viral infections (e.g., individuals aged 65 or older, or those with underlying medical conditions such as immunosuppression, hypertension, diabetes, or cardiovascular disease). Earlier in 2024, Brazil reported two fatalities in otherwise healthy non-pregnant women, along with five cases in pregnant individuals involving vertical transmission of the virus to the fetus, leading to fetal death or congenital abnormalities, including microcephaly. These were the first reported instances of death and adverse birth outcomes linked to Oropouche virus vertical transmission.

Diagnosis
Laboratory diagnosis is typically achieved through serum testing, with cerebrospinal fluid also testable in patients exhibiting signs of neuroinvasive disease. Diagnostic testing is accessible at certain public health laboratories (e.g., Wadsworth Center, NYS Department of Health) and the CDC. Additional diagnostic assays are under validation at the CDC and other public health laboratories. Healthcare providers are encouraged to contact their respective state, tribal, local, or territorial health department for further information and assistance with testing. For the latest testing and case reporting guidelines, visit the CDC’s website.

Co-Infection with Dengue Virus
In many regions, dengue outbreaks are occurring concurrently with Oropouche virus transmission. For patients suspected of Oropouche virus disease, ruling out dengue virus infection is crucial, as proper clinical management of dengue can significantly improve health outcomes. Other diagnostic considerations include chikungunya, Zika, leptospirosis, malaria, and infections caused by various bacterial or viral pathogens (e.g., rickettsia, group A streptococcus, rubella, measles, parvovirus, enteroviruses, adenovirus, Mayaro virus).

Treatment
There are no specific antiviral treatments or vaccines available for Oropouche virus disease. Symptomatic treatment may include rest, hydration, and the use of analgesics and antipyretics, with acetaminophen being the preferred first-line treatment for fever and pain. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided to reduce the risk of hemorrhage. Patients with more severe symptoms should be hospitalized for close monitoring and supportive care. Pregnant individuals with laboratory-confirmed Oropouche virus infection should be closely monitored during pregnancy, and newborns should be carefully evaluated.

Preventive Measures
Travelers to areas with Oropouche virus transmission should employ preventive measures to avoid exposure to biting midges and mosquitoes during travel and for three weeks after travel or if infected, during the first week of illness. These measures are critical to preventing further spread of the virus and its potential introduction into unaffected areas in the United States. Although Oropouche virus disease is not a nationally notifiable condition, the CDC encourages jurisdictions to voluntarily report cases to ArboNET, the national arboviral disease surveillance system.

Recommendations for Healthcare Providers

• Consider Oropouche virus infection in patients who have visited areas with known or suspected Oropouche virus circulation within two weeks of symptom onset, particularly if symptoms include abrupt onset of fever, headache, myalgia, arthralgia, photophobia, retro-orbital pain, or signs of neuroinvasive disease (e.g., stiff neck, altered mental status, seizures, limb weakness, CSF pleocytosis).
• Ensure the absence of respiratory symptoms (e.g., cough, rhinorrhea, shortness of breath).
• Test patients for other possible diseases, especially dengue, but do not delay contacting the relevant health department if Oropouche virus is strongly suspected.
• Rule out dengue virus infection in travelers with suspected Oropouche virus disease, as co-circulation with similar clinical presentations is common.
• Be aware that a high proportion of patients (approximately 70%) may experience recurrent symptoms days to weeks after initial recovery.
• Monitor pregnancies in individuals with laboratory-confirmed Oropouche virus infection and conduct thorough evaluations of infants.
• Counsel pregnant travelers on the risks associated with visiting areas with reported Oropouche virus transmission and recommend reconsidering non-essential travel.
• Manage travelers with suspected Oropouche virus disease using acetaminophen as the preferred first-line treatment for fever and pain; avoid the use of aspirin and other NSAIDs.
• Advise travelers to areas with Oropouche virus transmission to take precautions against insect bites during travel and for three weeks afterward, or if infected, during the first week of illness to prevent further spread.

Recommendations for Health Departments

• Disseminate Oropouche virus prevention messages to healthcare providers, travel health clinics, and the public.
• Conduct surveillance for Oropouche virus disease cases in travelers from areas with virus transmission, and remain vigilant for potential local transmission in areas where biting midges and mosquitoes are active.
• Stay updated on the CDC’s evolving testing and case reporting guidance.
• Assist healthcare providers with obtaining appropriate diagnostic testing for Oropouche virus infection.
• Voluntarily report confirmed and probable Oropouche virus infections to the CDC via ArboNET, the national surveillance system for arbovirus-borne diseases.
• Contact the CDC at eocevent495@cdc.gov if there is concern about local transmission in non-endemic areas.

Recommendations for Travelers

• All travelers can protect themselves from Oropouche, dengue, Zika, and other insect-borne viruses by preventing insect bites, including the use of Environmental Protection Agency (EPA)-registered insect repellents, wearing long-sleeved clothing, and staying in accommodations