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Oropouche fever

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Oropouche fever
Other names: Oropouche[1]
Areas of Bolivia, Brazil, and Peru with outbreaks of Oropouche fever[2]
SpecialtyInfectious diseases
SymptomsFever, headache, muscle pains[3]
ComplicationsMeningitis, encephalitis, possibly birth defects[3][1]
Usual onset3 to 10 days[3]
DurationLess than 7[1]
CausesOropouche virus (OROV) spread by midges or mosquitoes[3]
Diagnostic methodPCR testing, serology[3]
Differential diagnosisDengue, West Nile, yellow fever, Zika, chikungunya, Guama[4]
PreventionAvoiding bites[1]
TreatmentSymptomatic care[1]
PrognosisGenerally good[3]
Frequency> 0.5 million[3][4]

Oropouche fever is a viral infection that typically results in sudden onset of fever, headache, and muscle pains.[3][1] This generally lasts less than 7 days; thought, symptoms reoccur after a week or two in about half of people.[1] Time from exposure to symptom onset is generally 3 to 10 days.[3] Complications occasionally include meningitis, encephalitis, and possibly birth defects.[3][1]

It is caused by one of four types of Oropouche virus (OROV), an arbovirus of the Peribunyaviridae family.[3][5] It is spread by midges of the Culicoides paraensis type and less commonly mosquitoes.[3][5] It does not appear to spread directly between people.[4] Diagnosis based on symptoms alone is not accurate; however, better testing methods including PCR and serology are often not available.[3]

There is no vaccine or specific treatment.[1] Management is symptomatic with the use of acetaminophen, drinking sufficient fluids, and rest.[1] It is recommended that aspirin be avoided.[1] Prevention is by avoiding bites with fine-mesh mosquito nets, clothing which covers the limbs, and insect repellent that contains DEET.[1][5] Outcomes are generally good, with only two possibly associated deaths as of 2025.[5]

Oropouche fever is estimated to have occurred more than half a million times since it was discovered in 1955.[3][4] It occurs primarily as outbreaks in the Caribbean, Central America, and South America.[1] Regions were it occurs have been increasing.[3] In June 2024 it was confirmed in Cuba.[6][4] It is named after the area it was discovered, the Oropouche River in Trinidad and Tobago.[7]

Signs and symptoms

Oropouche fever is characterized as an acute febrile illness, meaning that it begins with a sudden onset of a fever followed by severe clinical symptoms.[8] It typically takes 4 to 8 days from the initial infection to start of symptoms.[9]

Fevers are the most common symptom with temperatures as high as 104F. Other symptoms may include chills, headache, myalgia, arthralgia, dizziness, photophobia, vomiting, joint pains, epigastric pain, and rashes.[10]

There also have been some cases where rashes resembles rubella and patients presented systematic symptoms including nausea, vomiting, diarrhea, conjunctive congestion, epigastric pain, and retro-orbitial pain.[9]

The initial febrile episode typically passes after a few days, but it is very common to have a reoccurrence of these symptoms with a lesser intensity.[9] Studies have shown this typically happens in about 60% of cases.[9]

Cause

The oropouche virus is an emerging infectious agent that causes the illness oropouche fever.[11] This virus is an arbovirus and is transmitted among sloths, marsupials, primates, and birds through the mosquitoes Aedes serratus and Culex quinquefaciatus.[12] The oropouche virus has evolved to an urban cycle infecting humans though midges as its main transporting vector.[12]

OROV was first described in Trinidad in 1955 when the prototype strain was isolated from the blood of a febrile human patient and from Coquillettidia venezuelensis mosquitoes.[13] In Brazil, OROV was first described in 1960 when it was isolated from a three-toed sloth (Bradypus tridactylus) and Ochlerotatus serratus mosquitoes captured nearby during the construction of the Belém-Brasilia Highway.[13] The oropouche virus is responsible for causing massive, explosive outbreaks in Latin American countries, making oropouche fever the second most common arboviral infection seen in Brazil.[14] So far the only reported cases of Oropouche fever have been in Brazil, Panama, Peru, and Trinidad and Tobago.[9]

ORO fever occurs mainly during the rainy seasons because there is an increase in breeding sites in the vector populations.[9] There has also been reports of the oropouche epidemics during the dry season but this is most likely due to the high population density of mosquitoes from the past rainy season.[9] Moreover, during the dry season there is a deceased chance of outbreaks which decreases the amount of midges this is because the amount of outbreaks is related to the number of human population that has not yet been exposed to this virus.[9]

  • Mosquitoes are how the oropouche virus can transfer infection from host to host causing Oropouche fever in humans.

    Mosquitoes are how the oropouche virus can transfer infection from host to host causing Oropouche fever in humans.

  • Urban (U) and sylvatic (S) transmission cycles of OROV

    Urban (U) and sylvatic (S) transmission cycles of OROV

Mechanism

Oropouche fever is caused by the oropouche virus (OROV) that belongs to the Peribunyaviridae family of arboviruses.[9] This virus is a single-stranded, negative sense RNA virus which is the cause of this disease.[10] There are no specific ultrastructural studies of the oropouche virus in human tissues that have been recorded to this date.[9] It is likely that this viral agent shares similar morphological characteristics with other members of the Orthobunyavirus genus.[9] Members of the Orthobunyavirus genus have a three part, single-stranded, negative sense RNA genome of small (S), medium (M) and large (L) RNA segments.[9] These segments function to encode nucleocapsids, glycoproteins and the RNA polymerase in that sequential order.[9] Through phylogenetic analysis of nucleocapsid genes in different oropouche virus strains, it has been revealed that there are three unique genotypes (I, II, III) that are currently spreading through Central and South America.[9]

Genomics

Genetic reassortment is said to be one of the most important mechanisms in explaining the viral biodiversity in orthobunyaviruses.[9] This occurs when two genetically related viruses infect the same cell at the same time forming a progeny virus and this virus holds various components of genetic L, M and S segments from the two parental viruses.[9] In reassortment, the S and L segments are the ones that are usually exchanged between species further, the S segment, that is coded by the nucleocapsid protein, and the L polymerase function together to create a replication of the viral genome. Due to this, one segment will restrict the molecular evolution of another segment and this is said to be inherited as a pair.[9] On the contrary, the M segment codes for viral glycoproteins and these could be more prone to mutations due to a higher selective pressure in their coding region because these proteins are major host range determinants.[9]

Pathogenesis

There is not a significant amount of information about the pathogenesis of OROV infections because there have been no recorded fatalities to date. It is known that within 2–4 days from the initial onset of systematic symptoms in humans, the presence of this virus is detected in the blood. In some cases this virus has also been recovered from the cerebrospinal fluid, but the route of invasion to the central nervous system remains unclear.[9] To further understand the pathogenesis of how this virus manifests in the body experimental studies using murine models have been performed.[15]

Mice models

BALB/c neonate mice were injected with the virus subcutaneously and presented symptoms five days after.[9] The mice had a high concentration of the replicating virus in the brain along with inflammation of the meninges and apoptosis of neurons without inflammation of the brain.[9] These findings confirmed the neurotropism of this virus, which means that this virus is capable of infecting nerve cells. Immunohistochemistry was used to reveal how this virus had access to the central nervous system.[9] The findings indicated that the OROV infection starts from the posterior parts of the brain and progresses toward the forebrain.[9] The oropouche virus spreads through the neural routes during early stages of the infection, reaching the spinal cord and traveling upward to the brain through brainstem with little inflammation.[9] As the infection progresses, the virus crosses the blood-brain barrier and spreads to the brain parenchyma leading to severe manifestations of encephalitis.[9] Damage to the brain parenchyma can result in the loss of cognitive ability or death.[16]

Diagnosis

Diagnosis of the oropouche infection is done through classic and molecular virology techniques.[9] These include:

  1. Virus isolation attempt in new born mice and cell culture (Vero Cells)[9]
  2. Serological assay methods, such as HI (hemagglutination inhibition), NT (neutralization test), and CF (complement fixation test) tests and in-house-enzyme linked immunosorbent assay for total immunoglobulin, IgM, and IgG detection using convalescent sera[9][11] (this obtained from recovered patients and is rich in antibodies against the infectious agent)
  3. Reverse transcription polymerase chain reaction (RT-PCR) and real time RT-PCR for genome detection in acute samples (sera, blood, and viscera of infected animals)[9]

Clinical diagnosis of oropouche fever is hard to perform due to the nonspecific nature of the disease, in many causes it can be confused with dengue fever or other arbovirus illness.[11]

Prevention

Prevention strategies include reducing the breeding of midges through source reduction (removal and modification of breeding sites) and reducing contact between midges and people. This can be accomplished by reducing the number of natural and artificial water-filled habitats and encourage the midge larvae to grow.[10]

Oropouche fever is present in epidemics so the chances of one contracting it after being exposed to areas of midgets or mosquitoes is rare.[10]

Treatment

Oropouche fever has no specific treatment, with efforts being symptomatic in nature. Analgesic and anti-inflammatory agents can help treat head and body pains. Ribavirin was not found useful in a mouse model of the disease.[3] Other recommendations include drinking sufficient fluids to prevent dehydration. Aspirin is not recommended as it can reduce blood clotting and prolong recovery time.[citation needed]

Prognosis

The infection is usually self-limiting and complications are rare. Symptoms usually last about a week but in extreme cases can be prolonged.[13] People usually recover fully with no long term ill effects.[8] There have been two recorded deaths as of 2025.[5]

Recent research

One study has focused on identifying OROV through the use of RNA extraction from reverse transcription-polymerase chain reaction.[14] This study revealed that OROV caused central nervous system infections in three patients. The three patients all had meningoencephalitis and also showed signs of clear lympho-monocytic cellular pattern in CSF, high protein, and normal to slightly decreased glucose levels indicating they had viral infections. Two of the patients already had underlying infections that can effect the CNS and immune system and in particular one of these patients has HIV/AIDS and the third patient has neurocysticercosis. Two patients were infected with OROV developed meningitis and it was theorized that this is due to them being immunocompromised. Through this it was revealed that it's possible that the invasion of the central nervous system by the oropouche virus can be performed by a previous blood-brain barrier damage.[14]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 "About Oropouche". Oropouche. CDC. 30 January 2025. Retrieved 27 February 2025.
  2. ↑ "Oropouche Fever in South America - Level 1 - Level 1 - Practice Usual Precautions - Travel Health Notices | Travelers' Health | CDC". wwwnc.cdc.gov. Archived from the original on 3 June 2024. Retrieved 4 June 2024. Archived 3 June 2024 at the Wayback Machine
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 Wesselmann, KM; Postigo-Hidalgo, I; Pezzi, L; de Oliveira-Filho, EF; Fischer, C; de Lamballerie, X; Drexler, JF (July 2024). "Emergence of Oropouche fever in Latin America: a narrative review". The Lancet. Infectious diseases. 24 (7): e439 – e452. doi:10.1016/S1473-3099(23)00740-5. PMID 38281494.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Zhang, Y; Liu, X; Wu, Z; Feng, S; Lu, K; Zhu, W; Sun, H; Niu, G (March 2024). "Oropouche virus: A neglected global arboviral threat". Virus research. 341: 199318. doi:10.1016/j.virusres.2024.199318. PMID 38224842.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "Oropouche virus disease". www.paho.org. PAHO. 7 February 2025. Retrieved 27 February 2025.
  6. ↑ "Rare Oropouche virus spotted in several cities for the first time, Cuba authorities say". Yahoo News. 30 May 2024.
  7. ↑ Kaslow, Richard A.; Stanberry, Lawrence R.; Duc, James W. Le (27 September 2014). Viral Infections of Humans: Epidemiology and Control. Springer. p. 175. ISBN 978-1-4899-7448-8. Archived from the original on 26 April 2025. Retrieved 27 February 2025. Archived 26 April 2025 at the Wayback Machine
  8. ↑ 8.0 8.1 Pinheiro, F.P; Travassos Da Rosa, Amelia P (January 1981). "Oropouche virus. I. A review of clinical, epidemiológical, and ecological findings". American Journal of Tropical Medicine and Hygiene. 30 (1): 149–160. doi:10.4269/ajtmh.1981.30.149. PMID 6782898. Archived from the original on 2023-04-09. Retrieved 2022-11-24 – via AJTMH. Archived 2023-04-09 at the Wayback Machine
  9. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 9.18 9.19 9.20 9.21 9.22 9.23 9.24 9.25 9.26 9.27 9.28 Travassos da Rosa, Jorge Fernando; de Souza, William Marciel; Pinheiro, Francisco de Paula; Figueiredo, Mário Luiz; Cardoso, Jedson Ferreira; Acrani, Gustavo Olszanski; Nunes, Márcio Roberto Teixeira (2017-05-03). "Oropouche Virus: Clinical, Epidemiological, and Molecular Aspects of a Neglected Orthobunyavirus". The American Journal of Tropical Medicine and Hygiene. 96 (5): 1019–1030. doi:10.4269/ajtmh.16-0672. ISSN 0002-9637. PMC 5417190. PMID 28167595.
  10. ↑ 10.0 10.1 10.2 10.3 Vasconcelos, Helena B.; Azevedo, Raimunda S. S.; Casseb, Samir M.; Nunes-Neto, Joaquim P.; Chiang, Jannifer O.; Cantuária, Patrick C.; Segura, Maria N. O.; Martins, Lívia C.; Monteiro, Hamilton A. O. (2009-02-01). "Oropouche fever epidemic in Northern Brazil: Epidemiology and molecular characterization of isolates". Journal of Clinical Virology. 44 (2): 129–133. doi:10.1016/j.jcv.2008.11.006. ISSN 1386-6532. PMID 19117799.
  11. ↑ 11.0 11.1 11.2 Saeed, Mohammad F.; Nunes, Marcio; Vasconcelos, Pedro F.; Travassos Da Rosa, Amelia P. A.; Watts, Douglas M.; Russell, Kevin; Shope, Robert E.; Tesh, Robert B.; Barrett, Alan D. T. (July 2001). "Diagnosis of Oropouche Virus Infection Using a Recombinant Nucleocapsid Protein-Based Enzyme Immunoassay". Journal of Clinical Microbiology. 39 (7): 2445–2452. doi:10.1128/JCM.39.7.2445-2452.2001. ISSN 0095-1137. PMC 88168. PMID 11427552.
  12. ↑ 12.0 12.1 Mourão, Maria Paula G.; Bastos, Michelle S.; Gimaque, João Bosco L.; Mota, Bruno Rafaelle; Souza, Giselle S.; Grimmer, Gustavo Henrique N.; Galusso, Elizabeth S.; Arruda, Eurico; Figueiredo, Luiz Tadeu M. (December 2009). "Oropouche Fever Outbreak, Manaus, Brazil, 2007–2008". Emerging Infectious Diseases. 15 (12): 2063–2064. doi:10.3201/eid1512.090917. ISSN 1080-6040. PMC 3044544. PMID 19961705.
  13. ↑ 13.0 13.1 13.2 Nunes MRT (2005). "Oropouche Virus Isolation, Southeast Brazil". Emerging Infectious Diseases. 11 (10): 1610–1613. doi:10.3201/eid1110.050464. PMC 3366749. PMID 16318707.
  14. ↑ 14.0 14.1 14.2 Bastos, Michele de Souza; Figueiredo, Luiz Tadeu Moraes; Naveca, Felipe Gomes; Monte, Rossicleia Lins; Lessa, Natália; Pinto de Figueiredo, Regina Maria; Gimaque, João Bosco de Lima; Pivoto João, Guilherme; Ramasawmy, Rajendranath (2012-04-01). "Short Report: Identification of Oropouche Orthobunyavirus in the Cerebrospinal Fluid of Three Patients in the Amazonas, Brazil". The American Journal of Tropical Medicine and Hygiene. 86 (4): 732–735. doi:10.4269/ajtmh.2012.11-0485. ISSN 0002-9637. PMC 3403753. PMID 22492162.
  15. ↑ Santos RI, Bueno-Júnior LS, Ruggiero RN, Almeida MF, Silva ML, Paula FE, Correa VM, Arruda E (10 October 2014). "Spread of Oropouche virus into the central nervous system in mouse". Viruses. 6 (10): 3827–3836. doi:10.3390/v6103827. PMC 4213564. PMID 25310583.
  16. ↑ "What Is the Brain Parenchyma? (with pictures)". wiseGEEK. Archived from the original on 2016-01-05. Retrieved 2017-12-12. Archived 2016-01-05 at the Wayback Machine

External links

Classification

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