Oropouche Virus: The Silent Threat of a Re-emerging Arbovirus

1. Context

Arboviral diseases are a group of infections that cause significant challenges to public health globally. Arboviral diseases are mainly transmitted by vectors such as mosquitoes, ticks, and midges ( 1 , 2 ). These vectors have the ability to transmit the viruses to humans and animals resulting in life-threatening diseases such as dengue, zika, chikungunya, malaria and yellow fever ( 3 , 4 ). Arboviruses are distributed worldwide, and arboviral infections range from mild to severe, occasionally resulting in death. Mosquitoes such as Anopheles, Aedes, and Culex are among the predominant vectors that transmit several arboviruses to humans ( 5 ). Hundreds of thousands of deaths were reported each year due to the arboviral diseases ( 6 , 7 ).

A large number of human disease-causing arboviruses belong to the Togaviridae, Flaviviridae, Bunyaviridae and Reoviridae families. These viruses predominately circulate in tropical and subtropical regions, largely due to the high prevalence of vector populations ( 5 ). Hence, there is a significant burden, particularly in low- and middle-income countries in tropical regions. For instance, dengue was responsible for over 6.5 million cases and more than 7,300 fatalities worldwide in 2023 ( 8 ). A higher number of dengue cases were reported in over 80 countries. In Asia, the highest numbers were recorded in Bangladesh (321,000), Viet Nam (369,000), and Thailand (150,000) ( 9 ). Before 2015, Oropouche was the second most prevalent arboviral disease after dengue in South America. Today, many arboviral diseases are re-emerging in previously unreported regions due to the complex interplay of various factors such as urbanization, climate change, population growth, and increased global trade and travel ( 10 , 11 ).

Arboviral infections such as Zika, Chikungunya and dengue have had a major impact on South America over the past decade ( 12 ). In addition, cases of Oropouche virus have been increasing in recent years. Oropouche virus is a reemerging arthropod-borne virus responsible for Oropouche fever, a disease characterized by severe acute febrile symptom. It is one of the neglected diseases, and its burden has often been overlooked due to significant underreporting. The virus was first identified in Trinidad and Tobago in 1955 ( 13 ) and until 2000, outbreaks were reported mainly in Brazil, Panama, and Peru. In 2023, the virus was reported in new areas of South America, highlighting its high potential to spread to non-endemic countries ( 14 ). This review presents an overview of the Oropouche virus, including its clinical features and pathogenesis.

2. Evidence Acquisition

2.1. Epidemiology

Oropouche virus is a spherical, enveloped virus (80 to 120 nm in diameter) belonging to the Peribunyaviridae family¸ order bunyavirales, and genus Orthobunyavirus (Simbu serogroup) ( 15 ). It is a negative-sense ribonucleic acid (RNA) virus consisting of three segments: small (S), medium (M), and large (L). The proteins encoded by these segments facilitates virus replication inside host cells and also help to evade the host immune response ( 16 - 18 ).

Oropouche fever was first reported in 1955, and subsequently, the virus was isolated from the blood of a symptomatic patient in a village of Vega de Oropouche, Trinidad ( 19 ). Since its identification, more than half a million human cases have been reported. The virus circulates throughout much of Central and South America, as well as the Caribbean ( 20 ). Oropouche virus fever is the most frequent arboviral disease after dengue fever ( 21 ). Although the virus was identified six decades ago, it has recently achieved increased attention due to its reemergence and outbreaks in different areas of South America during 2023-2024. its geographic range is expanding, where the virus is currently being reported in non-endemic areas ( 22 , 23 ).

Since 2023, a significant increase in Oropouche fever cases has been reported in Brazil and surrounding countries, including Bolivia, Colombia, Cuba, Dominican Republic, Ecuador, Guyana and Peru. From 2015 to 2022, Brazil recorded only a small number of cases (261) of Oropouche fever. However, in 2023, there was a significant surge, with confirmed cases reaching 831. In 2024, approximately 16,239 confirmed cases were reported in the Americas region, including four deaths, whereas 3,765 confirmed Oropouche cases were reported in 2025 (as of Feb 11, 2025) ( 24 - 26 ). The virus was reported for the first time in Cuba, Ecuador and Guyana in 2024 ( 27 ). Travel-associated cases were reported in the USA, Canada, Italy, Germany and Spain, all involving travelers who had visited Brazil or Cuba ( 14 , 28 ).

However, no local transmission has been reported in the USA. Two deaths associated with the Oropouche virus were confirmed by Brazilian Ministry of Health in the state of Bahia on July 25, 2024. Vertical transmission resulting in congenital infection, fetal death, and microcephaly in pregnant women was reported in Brazil in August 2024 ( 29 , 30 ). Brazil reported a case of encephalitis associated with this virus, 13 fetal deaths, three spontaneous miscarriages, and four cases of congenital anomalies (as of October 15, 2024) ( 31 ). These findings have raised serious concerns about the threat, this virus poses to public health.

2.2. Transmission

The virus exhibits both sylvatic and urban transmission cycles. In the sylvatic cycle, the vertebrate hosts include sloths (Bradypus tridactylus), non-human primates, and birds. In the urban cycle, humans are the primary hosts, and transmission occurs through the bite of infected midges- Culicoides paraensis (genus: Culicoides, Order: Diptera, Family: Ceratopogonidae) ( 32 , 33 ). The genus Culicoides includes vectors of more than 50 arboviruses of human and veterinary importance ( 26 ).

The mosquitoes such as Cx. quinquefasciatus, Cq. Venezuelensis, and Ae. serratus can also act as possible vectors and transmit the disease primarily in sylvatic environment ( 34 , 35 ). There is no evidence of human-to-human transmission reported so far. During the first week of illness, the virus has been detected in serum samples, but it is not detected beyond day 5 ( 36 ). Viral RNA can be detected using real-time reverse transcription-polymerase chain reaction (RT-PCR), while virus-specific neutralizing antibodies can be detected through plaque reduction neutralization tests (PRNTs). Currently, diagnostic or rapid tests based on antigens or immunoassays are not commercially available ( 37 , 38 ).

2.3. Symptoms and Treatment

Most symptoms are usually mild and self-limiting, appearing four to eight days after an infected bite and lasting up to seven days. The incubation period is variable, typically ranging from three to ten days ( 39 ). Symptoms resemble those of other mosquito-borne infections such as dengue, chikungunya, and  zika, making clinical differentiation challenging ( 40 , 41 ). In some cases, Oropouche virus fever goes undiagnosed due to mild symptoms or is misdiagnosed because of its similar clinical characteristics to other arboviral diseases ( 42 ). It presents with a sudden onset of fever (38-40°C), chills, headache, extreme weakness, joint pain, muscle aches, nausea, and vomiting ( 43 , 44 ). Other symptoms include diarrhea, bleeding, abdominal pain, retro-orbital pain, photophobia, dizziness, conjunctival injection.

The infection typically resolves within two to three weeks; however, in some cases, severe complications such as meningitis or encephalitis have been reported ( 45 ). Some affected individuals reported recurrent symptoms following the resolution of their initial illness ( 46 ). Although fatal outcomes are rare, mortality has been reported in Brazil ( 26 ).

Treatment is primarily supportive, consisting of rest, hydration, and the use of analgesics and antipyretics to alleviate the symptoms. Hospitalization might be necessary if the patient presents with severe symptoms or complications. Vaccine development efforts are currently underway to control Oropouche virus infection, including chemically inactivated, DNA-vectored, live attenuated, and protein-subunit approaches ( 38 , 39 , 44 ).

3. Results

Arboviral diseases are challenging to manage due to their complex transmission dynamics, unpredictable outbreaks, and limited treatment options. Research on vector competence studies, transmission and viral pathogenesis is essential. Due to the unpredictable nature of viral diseases, it is essential for all countries to be prepared for the unexpected. The local and national health authorities should focus on preventing small, localized viral outbreaks from escalating into epidemics or pandemics by implementing integrated surveillance systems, emergency response protocols, and community-based prevention strategies ( 47 ). As Oropouche virus spreads into new territories, epidemiological and entomological surveillance are critical to reinforcing the prevention measures. Early detection and differential diagnosis are essential for effective patient management and to help prevent potential virus transmission.

Currently, there are no licensed vaccines or specific antiviral therapies available to treat Oropouche virus disease. Plant-based expessionsystems can be utilized to produce immunogenic proteins of the Oropouche virus for vaccine development ( 45 ). The genetic diversity of the virus makes vaccine development a challenging task. Therefore, vector control and personal protection strategies appear to be the most effective prevention and control measures at present. Monitoring vectors is crucial, as they play an important role in disease transmission.

The risk of infection can be reduced by lowering midge populations through the control of breeding sites around at-risk communities, and by minimizing vector bites using mosquito nets, insect repellants, and insecticides ( 47 ). Further educating at-risk communities in endemic regions about the potential health threats posed by midge bites, along with personal protection options, can also significantly help prevent Oropouche virus transmission.

4. Conclusion

Oropouche virus is a neglected arbovirus that has recently emerged as a major public health threat, causing significant outbreaks in South America. Like other arboviral diseases, Oropouche virus fever has been considered as a neglected disease for the past six decades. Now, the Oropouche virus is reemerging and has become one of the most significant viral diseases in Latin America, likely to remain a considerable threat to global public health in the future. Hence, further research is essential to assess the disease burden, and there is an urgent need to develop effective vaccines to respond effectively to future outbreaks.

Acknowledgment

The authors are thankful to Karpagam Academy of Higher Education and DST-FIST (SR/FST/LS-I/2018/187 dt 20.12.2018) for the support.

Authors' Contribution

Study concept and design: B.S

Acquisition of data: B.S

Drafting of the manuscript: B.S., K.S

Critical revision of the manuscript: B.S., K.S

Ethics

Not applicable.

Conflict of Interest

The authors declare no conflict of interests.

Funding

This research received no external funding. This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data Availability

The data sharing is not applicable to this article as no new datasets were generated or analyzed during the current study.

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