A Comprehensive Review of the Neglected and Emerging Oropouche Virus

Abstract

Oropouche virus (OROV) is a neglected and emerging arbovirus that infects humans and animals in South and Central America. OROV is primarily transmitted to humans through the bites of infected midges and possibly some mosquitoes. It is the causative agent of Oropouche fever, which has high morbidity but low mortality rates in humans. The disease manifests in humans as high fever, headache, myalgia, arthralgia, photophobia, and, in some cases, meningitis and encephalitis. Additionally, a recent report suggests that OROV may cause fetal death, miscarriage, and microcephaly in newborns when women are infected during pregnancy, similar to the issues caused by the Zika virus (ZIKV), another mosquito-borne disease in the same regions. OROV was first reported in the mid-20th century in the Amazon basin. Since then, over 30 epidemics and more than 500,000 infection cases have been reported. The actual case numbers may be much higher due to frequent misdiagnosis, as OROV infection presents similar clinical symptoms to other co-circulating viruses, such as dengue virus (DENV), chikungunya virus (CHIKV), ZIKV, and West Nile virus (WNV). Due to climate change, increased travel, and urbanization, OROV infections have occurred at an increasing pace and have spread to new regions, with the potential to reach North America. According to the World Health Organization (WHO), over 10,000 cases were reported in 2024, including in areas where it was not previously detected. There is an urgent need to develop vaccines, antivirals, and specific diagnostic tools for OROV diseases. However, little is known about this surging virus, and no specific treatments or vaccines are available. In this article, we review the most recent progress in understanding virology, transmission, pathogenesis, diagnosis, host-vector dynamics, and antiviral vaccine development for OROV, and provide implications for future research directions.

Keywords: Oropouche virus; biting midge; host factors; pathogenesis.

Figure 1

Human OROV cases reported before and in 2024 in the South and Central America regions. The yellow areas show the cases reported before 2023, including the outbreaks in Argentina, French Guiana, Haiti, and Trinidad and Tobago. The red areas show the cases reported in 2024. As of 25 November 2024, confirmed OROV cases were reported from the Amazon region of Brazil (5785 cases, illustrated with a blue column), the non-Amazon region of Brazil (3778 cases), and Bolivia (356 cases), Colombia (74 cases), Ecuador (2 cases), Peru (936 cases), Cuba (603 cases), Guyana (2 cases), Barbados (2 cases), and Panama (1 case). Data were retrieved from the WHO [3].

Figure 2

Travel-related OROV transmission to the US and Canada in 2024. A total of 110 OROV cases were reported in the US (108 cases) and Canada (2 cases), with a travel history to Cuba. Among 108 cases reported from the six states of the US, two were neuroinvasive, and the others were non-neuroinvasive. Data were retrieved from the US CDC [5].

Figure 3

A schematic diagram showing the genome structure and the coded proteins of OROV. The diagram was drawn based on the sequence of the isolate BeH759021. GenBank Accession: L segment: KP691606.1, M segment: KP691607.1, and S segment: KP691608.1.

Figure 4

The sylvatic cycle and the urban cycle of OROV transmission. In the sylvatic cycle, potential reservoirs of the OROV include mammals such as sloths, non-human primates, and birds. The virus is maintained in nature between wild animals and forest-dwelling mosquitoes, particularly Culex species and the biting midge Culicoides paraensis. Infected humans from the sylvatic cycle can introduce the virus to urban areas, bridging the two transmission cycles. In the urban cycle, Cu. paraensis midges are the primary vector, and Cx. quinquefasciatus may also transmit OROV to humans. Besides arthropod vectors, human-to-human transmission may occur via mother-to-fetus, blood transfusion, and sexual transmission routes. The illustration was created in BioRender.com.