Oropouche virus: Infectious substances pathogen safety data sheet
Section I - Infectious agent
Name
Oropouche virus
Agent type
Virus
Taxonomy
Family
Peribunyaviridae
Genus
Orthobunyavirus
Species
Orthobunyavirus oropoucheense
Synonym or cross-reference
Oropouche virus (OROV) is an arbovirus that causes Oropouche feverFootnote 1Footnote 2.
Characteristics
Brief description
Similar to other Peribunyaviridae family members, OROV is an enveloped, spherical virus ranging from 80 to 120 nm in diameterFootnote 1Footnote 2. Its structure is characterized by a negative-sense, segmented, single-stranded RNA genomeFootnote 1. The genome has three segments designated as large (L), medium (M), and small (S)Footnote 3Footnote 4. The L segment consists of 6,852 nucleotides and encodes the RNA-dependent RNA polymerase. The M segment, which has 4,385 nucleotides, encodes the glycoproteins, Gn and Gc, and the non-structural protein, NSm. The S segment, consisting of 958 nucleotides, encodes the nucleocapsid protein (N) and a non-structural protein, NSsFootnote 1Footnote 3. Gn and Gc are translated into a polyprotein that is eventually post-translationally cleaved; they form the spikes that cover the viral envelope and are critical to viral entry, assembly, and release from host cellsFootnote 1. The host cell receptor for OROV has yet to be identifiedFootnote 4.
Phylogenetic analyses indicate there are four virus genotypes (I-IV) circulating in the Americas; all four genotypes are found in BrazilFootnote 2Footnote 3. Genotype I was also detected in Trinidad and Tobago, genotype II was found in Peru and Panama, genotype III was detected in Peru, and genotype IV was only isolated in BrazilFootnote 3. The relationship between genotype and severity of disease is unclearFootnote 1.
OROV belongs to the Simbu serogroup of the Orthobunyavirus genusFootnote 1Footnote 2Footnote 3Footnote 4. Genetic reassortment among orthobunyaviruses of the same serogroup occurs often, thus new viruses such as Iquitos virus (IQTV), Madre de Dios virus (MDDV) and Perdões virus (PDEV) have emergedFootnote 1Footnote 4Footnote 5. These viruses contain the S and L segments of OROV and the M segments of unidentified Simbu serogroup virusesFootnote 5.
Properties
The virus enters HeLa cells by clathrin-mediated endocytosis and is released to the cytoplasm through acidification of the endosomeFootnote 3. The details of the OROV replication cycle are unknown. In vitro studies with HeLa cells revealed that OROV replication induces apoptosis, suggesting that viral protein synthesis is necessary for the induction of apoptosisFootnote 3. The NSs protein is not incorporated into the viral particle but is critical in evading the host's immune response by inhibiting the interferon response which is critical for innate immunityFootnote 1. The virus is also capable of penetrating the blood-brain barrier using a Trojan-horse mechanismFootnote 1Footnote 2. The virus will travel through the bloodstream inside infected phagocytes, which makes it undetectable to the target organs and tissues.
Section II - Hazard identification
Pathogenicity and toxicity
Oropouche fever is an acute febrile illness that generally lasts for 2-7 daysFootnote 2. Common symptoms include fever (~39 °C), chills, headache, muscle and joint pain, malaise, dizziness, nausea, vomiting, photophobia, retro-ocular pain, and in rare occasions, skin rash appearing on trunk and armsFootnote 2Footnote 4. There may also be hemorrhagic signs such as spontaneous bleeding, petechiae, epistaxis, gingival bleeding, and neurological signs like meningitis or meningoencephalitisFootnote 2. Physical weakness and strength loss have also been noticed in some patients for a period of 2 - 4 weeksFootnote 2Footnote 4. Generally, the prognosis for Oropouche fever is good; however, it can lead to systemic infection and an inflammatory response in the central nervous system (CNS)Footnote 1Footnote 2. This is most often noticed in immunocompromised individuals and children, or patients with previous history of a blood-brain barrier disruptionFootnote 1Footnote 2. Symptoms, such as fever, headache, dizziness, muscle pain, and weakness, have reappeared one to two weeks after recovery in 60% of reported casesFootnote 2Footnote 4. There are no reports of long-term sequelae or additional recurrence after a full recoveryFootnote 1Footnote 4.
Vertical transmission of OROV may occur during pregnancyFootnote 6. In one case, a pregnant woman who had a recent close contact with a positive case of Oropouche fever, presented with fever, headache, and epigastric pain during the thirtieth week of gestation. Fetal death was confirmed, and genetic testing by reverse transcription followed by polymerase chain reaction (RT-PCR) with umbilical cord blood and organ tissue obtained from the fetus confirmed presence of OROV. In another suspected case, a pregnant woman presented with fever, headache, lumbago, skeletal pain, arthralgia, retro-orbital pain, chills, photophobia, nausea, pruritus and taste alteration. OROV was subsequently detected in serum by PCR. Uterine hemorrhage was observed and miscarriage occurred in the eighth week of gestation. Further, IgM antibodies against OROV have been detected in serum and cerebrospinal fluid (CSF) samples in four newborns with microcephaly. A causal relationship between OROV infection and neurological malformations has not yet been established, but teratogenic effects in animals infected with other Simbu viruses have been documentedFootnote 2Footnote 6.
Epidemiology
OROV is maintained in nature through urban and sylvatic transmission cycles in Central and South America, although outbreaks outside of these regions are being observedFootnote 2. More than 30 outbreaks have occurred in Brazil, Peru, Panama, and Trinidad and Tobago, with disease prevalence at 20% in both urban and rural populations in these regionsFootnote 2. OROV is mostly endemic to Brazil as it is a densely populated, tropical country whose environment is ideal for the propagation and maintenance of arthropod vectorsFootnote 2. Epidemiological surveillance in humans and wild mammals have shown that OROV is also circulating in Argentina, Bolivia, Colombia, Ecuador and Venezuela, and more recently in Haiti in 2014, French Guiana in 2020, and Cuba in 2024Footnote 1Footnote 2Footnote 4Footnote 7. It is estimated that over 500,000 people have been infected by OROV in 60 years, and the first confirmed death as a result of infection was reported in 2024 in Valença, BrazilFootnote 1Footnote 2Footnote 8. Case counts and fatalities are likely underestimated due to similar clinical presentations to other febrile illnesses caused by arboviruses circulating in the area (dengue, West Nile, yellow fever, Zika, chikungunya, Guama, Mayaro)Footnote 2Footnote 4.
OROV was first detected in 1955 in a forest worker in TrinidadFootnote 1. The first outbreak occurred in 1961 in Belém, Brazil, and involved 11,000 peopleFootnote 2Footnote 4. Between 1961 and 1978, seven outbreaks of Oropouche fever were reported in urban centers in that region with around 30,000 people becoming infectedFootnote 1Footnote 2. The two largest epidemics of Oropouche fever were recorded in 1980 in Belém and in 1981 in ManausFootnote 2. More than 100,000 people were infected with the virus, and in the epidemic in Belém, 4.1% of the cases developed neurological symptoms including meningitis or meningismus. From 1980 to 2005, only sporadic cases or self-limited outbreaks were reported in BrazilFootnote 2. In 2006, a large outbreak that infected 18,000 individuals was reported in two municipalities in BrazilFootnote 2. In 2020, there was an outbreak with 50 reported cases in a small village located in the Amazonian forest in French GuianaFootnote 9. The most recent outbreak of OROV took place in Cuba in 2024 with 74 cases reported across two provincesFootnote 7. Outbreaks demonstrate a seasonal pattern, with most taking place during the rainy season (January to June) due to the high density of vector populationsFootnote 3Footnote 4.
Oropouche fever affects all age groups, but there is some inconsistency in infection patterns of the different sexesFootnote 2Footnote 3. In some outbreaks, females were primarily infected, while other outbreaks show that men were the most affectedFootnote 3. Immunocompromised individuals and/or individuals with an underlying condition may be at a higher risk of developing neurological manifestations such as meningitisFootnote 2Footnote 10.
Host range
Natural host(s)
OROV is conserved in nature by an urban cycle and a sylvatic cycle, which are linked by humansFootnote 2. Humans are the sole vertebrate hosts in the urban cycleFootnote 2. The main vertebrate hosts involved in the sylvatic cycle have not been fully identified, but antibodies to OROV have been found in pale-throated three-toed sloths (Bradypus tridactylus), nonhuman primates such as capuchin monkeys (Sarajus spp.), black-and-gold howler monkeys (Alouatta caraya), black-tufted marmosets (Callithrix penicillata), rodents (Proechimys spp.), and birds (Fringillidae, Thaurapidae, Columbidae)Footnote 1Footnote 2.
Other host(s)
Mice and hamsters have been experimentally infectedFootnote 1Footnote 2.
Infectious dose
While the exact infectious dose of OROV in humans is unknown, subcutaneous infection of hamsters showed high viral load in plasma that reached a peak of 106.0 TCID50/mL on the 3rd day after infectionFootnote 3.
Incubation period
The incubation period is 3 to 8 daysFootnote 1Footnote 2Footnote 4.
Communicability
The preferred mode of transmission of OROV is injection via infected vectors, including the biting midge (Culicoides paraensis) and certain mosquitoes (Culex quinquefasciatus, Aedes aegypti, Ochlerotatus serratus)Footnote 1Footnote 2Footnote 11. During the period of high viremia after the incubation period, infected people can serve as source of the virus for Cu. paraensis for three to four daysFootnote 3Footnote 11. There is no evidence of horizontal transmission, but vertical transmission is under investigation and may occur during pregnancyFootnote 1Footnote 6. Accidental air-borne infection has been reported in laboratory conditions, which suggests that infection may occur as a result of inhalation of aerosolsFootnote 11Footnote 12.
Section III - Dissemination
Reservoir
In the sylvatic cycle, reservoirs include pale-throated three-toed sloths (Bradypus tridactylus), nonhuman primates such as capuchin monkeys (Sarajus spp.), black-and-gold howler monkeys (Alouatta caraya), black-tufted marmosets (Callithrix penicillata), rodents (Proechimys spp.), and birds (Fringillidae, Thaurapidae, Columbidae)Footnote 2.
Zoonosis
None.
Vectors
The primary vector in the urban cycle of transmission of OROV is the biting midge, Culicoides paraensis, who has caused epidemics that infect up to 100,000 individualsFootnote 1Footnote 2. The vectors involved in the sylvatic cycle include the mosquito species Cq. venezuelensis, Ae. serratus, Cx. quinquefasciatus and midges of the genus CulicoidesFootnote 2. Transmission is solely the responsibility of adult, female midges as they require blood meals to support their egg production and maturationFootnote 1. 96% of these midges feed on blood from humans and wild mammalsFootnote 1.
Section IV - Stability and viability
Drug susceptibility/resistance
Ribavirin, mycophenolic acid, and IFN-α have been tested in in vitro studies, but only IFN-α showed limited activityFootnote 4. Psoralens are effective in inactivating other members of the PeribunyaviridaeFootnote 13.
Susceptibility to disinfectants
Similar to other enveloped viruses, OROV could be inactivated by 2% glutaraldehyde, formalin, paraformaldehyde, 1% sodium hypochlorite, hydrogen peroxide, non-ionic surfactants (Tween-20 and Tween-80), ethyl alcohol, isopropyl alcohol, peracetic acid, quaternary ammonium compounds, and iodophor compoundsFootnote 14Footnote 15.
Physical inactivation
Specific parameters of inactivation are unknown for OROV, but in general, viral genomic RNA becomes denatured at temperatures higher than 60°CFootnote 13. There is a lack of data on the impact of gamma irradiation and UV radiation on OROV specifically; however, studies have been conducted on Rift Valley Fever virus (RVFV), which is also part of the Bunyaviricetes classFootnote 16Footnote 17. A gamma irradiation dose of 8 Mrads, including a 2x safety factor, is necessary for inactivation of 1 × 106 TCID50 of RVFV in a liquid medium containing proteinFootnote 16. A UV-A radiation energy level of 1000 µW/cm2 for 90 minutes and 20 µg/mL of 4'-aminomethyl-trioxsalen (a psoralen) are required to inactivate RVFV (107.8 TCID50/mL)Footnote 17.
Survival outside host
The viability of OROV outside of the host is unknown, but Puumala hantavirus, which belongs to the same order as OROV, remained infectious in bank vole cage beddings for 12-15 days at room temperature after removal of the infected animalsFootnote 18.
Section V - First aid/medical
Surveillance
Differential diagnosis is important in distinguishing Oropouche fever from other common arbovirus infections that are circulating in endemic areasFootnote 2. Peak viremia coincides with the onset of acute febrile illness, thus it is possible to measure viral RNA in the blood during this timeFootnote 4. RT-PCR is used for rapid detection of OROV in serum and CSF samples; the primer will typically target the S segment's conserved sequenceFootnote 2. Because of this, RT-PCR detection methods cannot be considered OROV-specific as they cannot distinguish OROV strains from OROV-like reassortantsFootnote 4. Patients will also begin generating IgM and IgG antibodies 1 day to 2 weeks after disease onset which allows for serologic testingFootnote 4. IgG and IgM enzyme-linked immunosorbent assays (ELISA) are used to detect OROV in convalescent sera and distinguish it from other arbovirusesFootnote 3Footnote 4. Other available methods include plaque reduction neutralization test (PRNT), complement fixation test (CFT), hemagglutination inhibition (HI), enzyme immunoassay-immunocytochemistry (EIA-ICC), immunofluorescence (IF), and cell cultureFootnote 2Footnote 11.
Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.
First aid/treatment
Currently, there are no specific treatments for OROV infection and clinical intervention is based solely on easing the symptoms and providing supportive care through fever management and pain reliefFootnote 1Footnote 2Footnote 11.
Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.
Immunization
No vaccine currently available, however many vaccine candidates are being studied, one of which is a live attenuated vaccine that was shown to be safe and immunogenic in a phase I clinical trialFootnote 1Footnote 4.
Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.
Prophylaxis
There are no pre or post-exposure measures available to prevent infection or disease with OROVFootnote 1Footnote 2Footnote 4.
Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.
Section VI - Laboratory hazard
Laboratory-acquired infections
Pre-1981, one laboratory worker was accidentally infected orally and another worker was most likely infected by the respiratory routeFootnote 19.
Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.
Sources/specimens
Blood, serum, CSF, urine, saliva, and placenta can contain OROVFootnote 1Footnote 2Footnote 6Footnote 20Footnote 21.
Primary hazards
Bites of an infected arthropod vector is the primary hazard associated with exposure to OROVFootnote 1Footnote 2Footnote 4Footnote 11.
Special hazards
None.
Section VII - Exposure controls/personal protection
Risk group classification
Orthobunyavirus oropoucheense is a Risk Group 3 Human Pathogen, a Risk Group 2 Animal Pathogen, and a Security Sensitive Biological Agent (SSBA)Footnote 22.
Containment requirements
Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.
Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.
Protective clothing
The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.
Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.
Other precautions
All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.
Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measuresFootnote 23Footnote 24.
Section VIII - Handling and storage
Spills
Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with disinfectant before clean up (Canadian Biosafety Handbook).
Disposal
Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).
Storage
The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.
SSBA: Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.
An inventory of RG3 and SSBA toxins in long-term storage, to be maintained and to include:
- specific identification of the regulated materials
- a mechanism that allows for the detection of a missing or stolen sample in a timely manner
Section IX - Regulatory and other information
Canadian regulatory information
Controlled activities with Oropouche virus require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). Oropouche virus is a non-indigenous terrestrial animal pathogen in Canada; therefore, importation of Oropouche virus requires an import permit under the authority of the Health of Animals Regulations (HAR), issued by the Canadian Food Inspection Agency.
Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.
The following is a non-exhaustive list of applicable designations, regulations, or legislations:
- Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
- Health of Animals Act and Health of Animals Regulations
- Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
Last file update
July, 2024
Prepared by
Centre for Biosecurity, Public Health Agency of Canada.
Disclaimer
The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.
Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.
Copyright © Public Health Agency of Canada, 2024, Canada
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