27 AGO 2024 · Oropouche virus (OROV), a member of the Peribunyaviridae family, is an emerging arbovirus of significant public health concern in South and Central America. Colloquially known as "Sloth Fever," OROV infection causes a febrile illness in humans with symptoms similar to other tropical diseases, complicating diagnosis and potentially leading to underreporting. This comprehensive review examines the current state of knowledge regarding OROV, including its virology, transmission cycles, epidemiology, clinical manifestations, diagnostic challenges, and potential control strategies. The review also explores the ecological and anthropogenic factors influencing OROV's emergence and spread, as well as the virus's potential for urban adaptation. By synthesizing the latest research and identifying knowledge gaps, this article aims to provide a foundation for future studies and public health interventions targeting OROV.
First isolated in Trinidad and Tobago in 1955, Oropouche virus has since emerged as a significant cause of arboviral disease in the Amazon region and beyond. The virus's ability to utilize both sylvatic and urban transmission cycles, coupled with the expansion of human activities into endemic areas, has raised concerns about its potential for widespread outbreaks. Despite its impact, OROV remains understudied compared to other arboviruses such as dengue or Zika, highlighting the need for increased research attention and public health preparedness.
Oropouche virus is a negative-sense, single-stranded RNA virus belonging to the genus Orthobunyavirus within the Peribunyaviridae family. The OROV genome consists of three segments: large (L), medium (M), and small (S). The L segment encodes the RNA-dependent RNA polymerase, the M segment encodes the surface glycoproteins (Gn and Gc) and a nonstructural protein (NSm), and the S segment encodes the nucleocapsid protein (N) and a nonstructural protein (NSs) in overlapping reading frames.
Recent phylogenetic analyses have identified four distinct genotypes of OROV (I, II, III, and IV), with genotype I being the most widely distributed. Understanding the genetic diversity of OROV is crucial for developing effective diagnostic tools and potential vaccines, as well as for tracking the virus's evolution and spread.
OROV maintains complex transmission cycles involving both sylvatic and urban environments. In sylvatic cycles, the virus circulates among forest-dwelling animals, with evidence suggesting that sloths, non-human primates, and birds may serve as reservoir hosts. The primary vector in sylvatic transmission is believed to be the midge Culicoides paraensis, colloquially known as "no-see-ums" due to their small size.
The urban transmission cycle, which is responsible for human outbreaks, primarily involves C. paraensis as well. However, recent studies have implicated the mosquito Culex quinquefasciatus as a potential secondary vector in urban settings. This adaptation to a common urban mosquito species raises concerns about OROV's potential for sustained human-to-human transmission in densely populated areas.
The ability of OROV to utilize multiple vectors and adapt to urban environments presents significant challenges for vector control strategies and highlights the need for integrated approaches to disease management.
Since its discovery, OROV has been responsible for numerous outbreaks across South and Central America. Brazil has reported the majority of cases, with significant outbreaks occurring in the states of Pará, Amazonas, and Acre. Other countries reporting OROV activity include Peru, Panama, Trinidad and Tobago, and more recently, Ecuador.
Estimating the true incidence of OROV infection is challenging due to similarities with other arboviral diseases and limited surveillance in many endemic areas. Some studies suggest that OROV may be responsible for up to 30% of febrile illnesses in some regions during outbreak periods. The virus exhibits a seasonal pattern, with most cases occurring during the rainy season when vector populations are at their peak.
Seroprevalence studies in endemic areas have shown antibody rates ranging from 15% to 60%, indicating widespread exposure to the virus. However, these figures may underestimate the true extent of OROV circulation due to cross-reactivity with other closely related viruses.
Clinical Manifestations and Pathogenesis
OROV infection in humans typically results in an acute febrile illness lasting 3-7 days. Common symptoms include:
Sudden onset of high fever (38-39°C)
Severe headache, often described as incapacitating
Myalgia and arthralgia
Dizziness and photophobia
Nausea and vomiting
Skin rash (in some cases)
While most infections are self-limiting, some patients may experience a biphasic illness with recurrence of symptoms after a brief asymptomatic period. Severe complications are rare but have been reported, including meningitis and meningoencephalitis.
The pathogenesis of OROV infection remains poorly understood. Limited studies suggest that the virus may induce a pro-inflammatory response, with elevated levels of cytokines such as TNF-α, IL-6, and IL-1β observed in infected individuals. Further research is needed to elucidate the mechanisms of viral replication, tissue tropism, and host immune responses to OROV.
Accurate diagnosis of OROV infection is crucial for appropriate patient management and epidemiological surveillance. However, the nonspecific nature of OROV symptoms and its co-circulation with other arboviruses pose significant diagnostic challenges. Current diagnostic methods include:
Molecular detection: RT-PCR assays targeting the S segment are the gold standard for acute infection diagnosis.
Serological tests: IgM and IgG ELISA assays are available but may cross-react with antibodies to other orthobunyaviruses.
Virus isolation: While definitive, this method is time-consuming and requires specialized biosafety facilities.
Improving the specificity and accessibility of diagnostic tools, particularly rapid tests suitable for field use, remains a priority for OROV research.
Currently, there is no specific antiviral treatment for OROV infection. Management is primarily supportive, focusing on symptom relief and maintaining hydration. Given the lack of specific therapeutics, prevention strategies are crucial for controlling OROV transmission. These include:
Vector control measures: Targeting both midges and mosquitoes through insecticide use, habitat reduction, and personal protection (e.g., repellents, bed nets).
Environmental management: Reducing standing water and improving sanitation to limit vector breeding sites.
Public education: Raising awareness about OROV and promoting preventive behaviors.
Surveillance and early warning systems: Implementing robust monitoring programs to detect outbreaks early.
Vaccine development for OROV is in its early stages, with some preclinical studies showing promise. However, significant challenges remain, including the need for cross-protection against multiple genotypes and potential interference from pre-existing immunity to related viruses.
Ecological and Anthropogenic Factors Influencing OROV Emergence
Several factors contribute to the emergence and spread of OROV:
Deforestation and land-use changes: Altering sylvatic habitats may increase human-vector contact and disrupt natural transmission cycles.
Climate change: Shifting temperature and rainfall patterns may expand the range of OROV vectors.
Urbanization: Rapid, unplanned urban growth can create ideal conditions for vector proliferation and virus transmission.
Globalization and travel: Increased human movement may facilitate the introduction of OROV into new areas.
Understanding these factors is crucial for predicting and mitigating future OROV outbreaks.