By Jake Scott, MD
Clinical Assistant Professor, Infectious Diseases and Geographic Medicine, Stanford University School of Medicine; Antimicrobial Stewardship Program Medical Director, Stanford Health Care Tri-Valley
SYNOPSIS: Oropouche virus is an arthropod-borne virus that has been primarily endemic to the Amazon region. The incidence of Oropouche virus disease has significantly increased over the past few years, and recent outbreaks have been reported in areas without previous endemic transmission and have led to fatalities and vertical transmission resulting in adverse pregnancy outcomes.
SOURCE: Morrison A, White JL, Hughes HR, et al. Oropouche virus disease among U.S. travelers — United States, 2024. MMWR Morb Mortal Wkly Rep 2024;73:769-773.
Oropouche virus, which is a member of the family Bunyaviridae, genus Orthobunyavirus, is a ribonucleic acid (RNA) virus that causes Oropouche virus disease in humans.1 It is primarily transmitted in rural, forested areas by the biting midge, Culicoides paraensis.1 The sylvatic transmission cycle involves non-human primates and sloth reservoir hosts, as well as birds and mosquitos.2 Urban transmission primarily involves humans as the amplifying host and the biting midge as the primary vector. Transmission appears to be highest during the rainy season when C. paraensis tends to breed more.3
Clinical manifestations are similar to those of other arboviral diseases, such as dengue, Zika, and chikungunya, and they all can mimic other infectious diseases, such as influenza, malaria, leptospirosis, and ehrlichiosis. The incubation period typically is three to 10 days, and illness is characterized by sudden-onset fever, chills, headache, myalgias, arthralgias, retro-orbital pain, nausea, vomiting, diarrhea, abdominal pain, and maculopapular rash.4 Although most cases are mild and spontaneously resolve within a few days, hemorrhagic manifestations (e.g., petechiae, epistaxis, gingival bleeding, and menorrhagia) and neurologic complications (e.g., meningoencephalitis) have been reported.5,6 High rates of recurrent illness within days to weeks after resolution of initial symptoms have been reported.7
The virus initially was isolated in 1955 from a febrile forest worker in the South Oropouche area of Trinidad; neutralizing antibodies also were found in the blood of cebus and howler monkeys on the island.8 Based on molecular epidemiologic data, the virus likely originated in Northern Brazil in the late 18th century.9,10 The first known large outbreak of Oropouche virus disease occurred in 1961 in the Pará state, Brazil, where approximately 11,000 people were infected.7 Subsequent outbreaks were confined to Pará state, Brazil, until 1980.7 Since then, the virus has been detected in other Amazonian regions of South America, as well as in Panama, and Trinidad and Tobago.1
Between 2015 and 2022, 261 cases of Oropouche virus disease were reported in Brazil.11 However, the number of cases in Brazil surged to 831 in 2023, and to 7,497 by Aug. 6, 2024.11 Two deaths attributed to Oropouche infection were reported in Brazil in 2024. The first fatal case was a 24-year-old female resident of Bahia state with no known comorbidities who became ill on March 23, 2024.12 She initially developed fever, headache, retro-orbital pain, myalgia, severe abdominal pain, diarrhea, nausea, and vomiting. She sought medical attention multiple times and was discharged without outpatient management until her condition worsened and she was hospitalized three days after the onset of symptoms. Within 13 hours of hospitalization, she developed progressively worsening hypotension and hypoxemic respiratory failure and died due to a cardiorespiratory arrest. The second fatal case was a 21-year-old female with no known comorbidities who also was a resident of Bahia state. She developed symptoms on June 5, 2024, which included fever, myalgia, headache, retro-orbital pain, lower extremity pain, asthenia, and arthralgias. Four days later, she developed an erythematous rash, petechiae, and mucosal bleeding. She died two hours after hospital admission.12
Cases of vertical transmission of Oropouche infection also have been reported in Brazil. The first documented case, recorded on Aug. 2, 2024, in the state of Pernambuco, resulted in fetal death.11 A subsequent case was reported on Aug. 8, 2024. In this case, a neonate was born with congenital abnormalities attributed to vertical transmission of Oropouche infection, which included microcephaly, ventriculomegaly, agenesis of corpus callosum, and joint malformations. The infant died 47 days later.11
Oropouche virus recently emerged in Cuba, and outbreaks that occurred between December 2023 and June 2024 resulted in travel-associated cases among 18 European and 21 United States residents who had traveled to Cuba.13 Among the U.S. travelers, the diagnosis of Oropouche virus disease was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR) in 13 patients, by 90% plaque reduction neutralization test (PRNT90) in seven patients, and by both assays in one patient. The median age of these patients was 48 years (range 15-94 years) and 48% were female. The most commonly reported symptoms were fever (95%), myalgia (86%), headache (76%), fatigue or malaise (62%), and arthralgia (57%). Less commonly reported symptoms included diarrhea (48%), abdominal pain (29%), nausea or vomiting (29%), rash (29%), retro-orbital pain (24%), back pain (19%), and mucosal bleeding (5%). Three of the 21 patients were hospitalized and no deaths were reported.
Treatment of Oropouche virus disease is symptomatic and supportive care. There are no antiviral drugs or vaccines available. Preventive strategies include vector control measures, such as identifying and eliminating vector breeding and resting sites, and measures to prevent vector bites, such as protective mesh nets, clothing, and repellents.
Commentary
The recent rise in Oropouche virus disease, the expansion of transmission beyond regions previously known to have endemic transmission, and the first reports of deaths and vertical transmission underscore the importance of rapidly developing robust detection and surveillance systems and strengthening efforts to expand diagnostic and preventive capabilities. Oropouche virus disease should be considered in a patient who has resided in or traveled to an area with known Oropouche virus circulation who develops sudden-onset fever, headache, myalgia, arthralgia, photophobia, retro-orbital pain, and signs of meningoencephalitis. It also is important to note that recurrent symptoms are relatively common, especially compared to other similar infectious diseases, and that vertical transmission with adverse pregnancy outcomes can occur. Pregnant persons who plan to travel to areas where Oropouche virus is in circulation should be counseled about the risk of infection.
References
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- Sciancalepore S, Schneider MC, Kim J, et al. Presence and multi-species spatial distribution of Oropouche virus in Brazil within the One Health Framework. Trop Med Infect Dis 2022;7:111.
- Mourão MPG, de Souza Bastos M, de Figueiredo RMP, et al. Arboviral diseases in the Western Brazilian Amazon: A perspective and analysis from a tertiary health & research center in Manaus, State of Amazonas. Rev Soc Bras Med Trop 2015;48 (Suppl 1):20-26.
- Sakkas H, Bozidis P, Franks A, Papadopoulou C. Oropouche fever: A review. Viruses 2018;10:175.
- Mourãão MPG, Bastos MS, Gimaqu JBL, et al. Oropouche fever outbreak, Manaus, Brazil, 2007-2008. Emerg Infect Dis 2009;15:2063-2064.
- Vernal S, Martini CCR, da Fonseca BAL. Oropouche virus-associated aseptic meningoencephalitis, southeastern Brazil. Emerg Infect Dis 2019;25:380-382.
- da Silva Azevedo RS, Nunes MRT, Chiang JO, et al. Reemergence of Oropouche fever, northern Brazil. Emerg Infect Dis 2007;13:912-915.
- Anderson CR, Spence L, Downs WG, Aitken TH. Oropouche virus: A new human disease agent from Trinidad, West Indies. Am J Trop Med Hyg 1961;10:574-578.
- Romero-Alvarez D, Escobar LE. Oropouche fever, an emergent disease from the Americas. Microbes Infect 2018;20:135-146.
- Vasconcelos HB, Nunes MRT, Casseb LMN, et al. Molecular epidemiology of Oropouche virus, Brazil. Emerg Infect Dis 2011;17:800-806.
- Martins-Filho PR, Carvalho TA, Dos Santos CA. Oropouche fever: Reports of vertical transmission and deaths in Brazil. Lancet Infect Dis 2024; Aug 22:S1473-3099(24)00557-7.
- Bandeira AC, da Silva Barbosa ACFN, Souza M, da Costa Saavedra R. Clinical profile of Oropouche fever in Bahia, Brazil: Unexpected fatal cases. Preprint. Published online July 16, 2024. doi:10.1590/SciELOPreprints.9342.
- Morrison A, White JL, Hughes HR, et al. Oropouche virus disease among U.S. Travelers — United States, 2024. MMWR Morb Mortal Wkly Rep 2024;73:769-773.
