Oropouche fever

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Oropouche fever
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Mosquitoes are how the oropouche virus can transfer infection from host to host causing Oropouche fever in humans.
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Oropouche fever is a tropical viral infection transmitted by biting midges and mosquitoes from the blood of sloths to humans. This disease is named after the region where it was first discovered and isolated at the Trinidad Regional Virus Laboratory in 1955 by the Oropouche River in Trinidad and Tobago. [1] Oropouche fever is caused by a specific arbovirus, the Oropouche virus (OROV), of the Bunyaviridae family.

Contents

Large epidemics are common and very swift, one of the earliest largest having occurred at the city of Belém, in the Brazilian Amazon state of Pará, with 11,000 recorded cases. In the Brazilian Amazon, oropouche is the second most frequent viral disease, after dengue fever. Several epidemics have generated more than 263,000 cases, of which 130,000 alone occurred in the period from 1978 to 1980. [2] Presently, in Brazil alone it is estimated that more than half a million cases have occurred. Nevertheless, clinics in Brazil may not have adequate testing reliability as they rely on symptoms rather than PCR viral sequencing, which is expensive and time consuming, in many cases there may be co-infection with other similar mosquito-borne viruses. [3]

Symptoms and signs

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. [4] It typically takes 4 to 8 days from the incubation period to first start noticing signs of infection, beginning from the bite of the infected mosquito or midge. [5]

Fevers are the most common symptom with temperatures as high as 104F. Clinical symptoms include chills, headache, myalgia, arthralgia, dizziness, photophobia, vomiting, joint pains, epigastric pain, and rashes. [6]

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. [5]

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. [5] Studies have shown this typically happens in about 60% of cases. [5]

Cause

Oropouche orthobunyavirus
Virus classification Red Pencil Icon.png
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Ellioviricetes
Order: Bunyavirales
Family: Peribunyaviridae
Genus: Orthobunyavirus
Species:
Oropouche orthobunyavirus

The oropouche virus is an emerging infectious agent that causes the illness oropouche fever. [7] This virus is an arbovirus and is transmitted among sloths, marsupials, primates, and birds through the mosquitoes Aedes serratus and Culex quinquefaciatus. [3] The oropouche virus has evolved to an urban cycle infecting humans though midges as its main transporting vector. [3]

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. [1] 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. [1] 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. [8] So far the only reported cases of Oropouche fever have been in Brazil, Panama, Peru, and Trinidad and Tobago. [5]

ORO fever occurs mainly during the rainy seasons because there is an increase in breeding sites in the vector populations. [5] 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. [5] 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. [5]

Mechanism

Oropouche fever is caused by the oropouche virus (OROV) that belongs to the Peribunyaviridae family of arboviruses. [5] This virus is a single-stranded, negative sense RNA virus which is the cause of this disease. [6] There are no specific ultrastructural studies of the oropouche virus in human tissues that have been recorded to this date. [5] It is likely that this viral agent shares similar morphological characteristics with other members of the Orthobunyavirus genus. [5] 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. [5] These segments function to encode nucleocapsids, glycoproteins and the RNA polymerase in that sequential order. [5] 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. [5]

Genomic Reassortment

Genetic reassortment is said to be one of the most important mechanisms in explaining the viral biodiversity in orthobunyaviruses. [5] 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. [5] 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. [5] 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. [5]

Pathogenesis

There is not a significant amount of information about regarding the natural 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. [5] To further understand the pathogenesis of how this virus manifests in the body experimental studies using murine models have been performed. [9]

Murine Models

BALB/c neonate mice were treated with this virus subcutaneously and presented clinical symptoms five days after inoculation. [5] The mice revealed a high concentration of the replicating virus in the brain along with inflammation of the meninges and apoptosis of neurons without encephalitis, [5] which is inflammation of the brain due to an infection. [5] 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. [5] The findings indicated that the OROV infection starts from the posterior parts of the brain and progresses toward the forebrain. [5] 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. [5] As the infection progresses, the virus crosses the blood-brain barrier and spreads to the brain parenchyma leading to severe manifestations of encephalitis. [5] Damage to the brain parenchyma can result in the loss of cognitive ability or death. [10]

Diagnosis

Diagnosis of the oropouche infection is done through classic and molecular virology techniques. [5] These include:

  1. Virus isolation attempt in new born mice and cell culture (Vero Cells) [5]
  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 [5] [7] (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) [5]

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. [7]

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. [6]

Oropouche fever is present in epidemics so the chances of one contracting it after being exposed to areas of midgets or mosquitoes is rare. [6]

Treatment

Oropouche Fever has no cure or specific therapy so treatment is done by relieving the pain of the symptoms through symptomatic treatment. Certain oral analgesic and anti-inflammatory agents can help treat headaches and body pains. In extreme cases of oropouche fever the drug, Ribavirin is recommended to help against the virus. This is called antiviral therapy. Treatments also consist of drinking plenty of fluids to prevent dehydration. Aspirin is not a recommended choice of drug because it can reduce blood clotting and may aggravate the hemorrhagic effects and prolong recovery time.[ citation needed ]

Prognosis

The infection is usually self-limiting and complications are rare. This illness usually lasts for about a week but in extreme cases can be prolonged. [1] Patients usually recover fully with no long term ill effects. There have been no recorded fatalities resulting from oropouche fever. [4]

Recent Research

One study has focused on identifying OROV through the use of RNA extraction from reverse transcription-polymerase chain reaction. [8] 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. [8]

Related Research Articles

<span class="mw-page-title-main">Arbovirus</span> Common name for several species of virus

Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term arbovirus is a portmanteau word. Tibovirus is sometimes used to more specifically describe viruses transmitted by ticks, a superorder within the arthropods. Arboviruses can affect both animals and plants. In humans, symptoms of arbovirus infection generally occur 3–15 days after exposure to the virus and last three or four days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and viral hemorrhagic fever may also occur.

<i>Bunyavirales</i> Order of negative-sense single-stranded RNA viruses

Bunyavirales is an order of segmented negative-strand RNA viruses with mainly tripartite genomes. Member viruses infect arthropods, plants, protozoans, and vertebrates. It is the only order in the class Ellioviricetes. The name Bunyavirales derives from Bunyamwera, where the original type species Bunyamwera orthobunyavirus was first discovered. Ellioviricetes is named in honor of late virologist Richard M. Elliott for his early work on bunyaviruses.

Lymphocytic choriomeningitis (LCM) is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. Its causative agent is lymphocytic choriomeningitis mammarenavirus (LCMV), a member of the family Arenaviridae. The name was coined by Charles Armstrong in 1934.

Chandipura vesiculovirus (CHPV) is a member of the Rhabdoviridae family that is associated with an encephalitic illness in humans. It was first identified in 1965 after isolation from the blood of two patients from Chandipura village in Maharashtra state, India and has been associated with a number of otherwise unexplained outbreaks of encephalitic illness in central India. The most recent occurred in Andhra Pradesh and Maharashtra in June–August 2003 with 329 children affected and 183 deaths. Further sporadic cases and deaths in children were observed in Gujarat state in 2004.

Bwamba orthobunyavirus (BWAV) belongs to the genus Orthobunyavirus and the order Bunyavirales RNA viruses. BWAV is present in large parts of Africa, endemic in Mozambique, Tanzania and Uganda. It is transmitted to humans through mosquito bites and results in a brief benign generalised infection with headache, skin rash, diarrhea and joint pain and lasts 4–5 days. The animal reservoir of the virus includes birds, monkeys and donkeys.

<i>Semliki Forest virus</i> Species of virus

The Semliki Forest virus is an alphavirus found in central, eastern, and southern Africa. It was first isolated from mosquitoes in the Semliki Forest, Uganda by the Uganda Virus Research Institute in 1942 and described by Smithburn and Haddow. It is known to cause disease in animals including humans.

Mokola lyssavirus, commonly called Mokola virus (MOKV), is a RNA virus related to rabies virus that has been sporadically isolated from mammals across sub-Saharan Africa. The majority of isolates have come from domestic cats exhibiting symptoms characteristically associated to rabies virus infection.

California encephalitis orthobunyavirus type strain California encephalitis virus was discovered in Kern County, California, and causes encephalitis in humans. Encephalitis is an acute inflammation of the brain that can cause minor symptoms, such as headaches, to more severe symptoms such as seizures. Mosquitoes serve as its carrier and for this reason this virus is known as an arbovirus.

<i>Thogotovirus</i> Genus of viruses

Thogotovirus is a genus of enveloped RNA viruses, one of seven genera in the virus family Orthomyxoviridae. Their single-stranded, negative-sense RNA genome has six or seven segments. Thogotoviruses are distinguished from most other orthomyxoviruses by being arboviruses – viruses that are transmitted by arthropods, in this case usually ticks. Thogotoviruses can replicate in both tick cells and vertebrate cells; one subtype has also been isolated from mosquitoes. A consequence of being transmitted by blood-sucking vectors is that the virus must spread systemically in the vertebrate host – unlike influenza viruses, which are transmitted by respiratory droplets and are usually confined to the respiratory system.

Oropouche orthobunyavirus (OROV) is one of the most common orthobunyaviruses. When OROV infects humans, it causes a rapid fever illness called Oropouche fever. OROV was originally reported in Trinidad and Tobago in 1955 from the blood sample of a fever patient and from a pool of Coquillettidia venezuelensis mosquitoes. In 1960, OROV was isolated from a sloth and a pool of Ochlerotatus serratus mosquitoes in Brazil. The virus is considered a public health threat in tropical and subtropical areas of Central and South America, with over half a million infected people as of 2005. OROV is considered to be an arbovirus due to the method of transmission by the mosquitoes Aedes serratus and Culex quinquefasciatus among sloths, marsupials, primates, and birds.

<i>Orthobunyavirus</i> Genus of viruses

Orthobunyavirus is a genus of the Peribunyaviridae family in the order Bunyavirales. There are currently ~170 viruses recognised in this genus. These have been assembled into 103 species and 20 serogroups.

Bunyamwera orthobunyavirus (BUNV) is a negative-sense, single-stranded enveloped RNA virus. It is assigned to the Orthobunyavirus genus, in the Bunyavirales order.

Toscana phlebovirus (TOSV) is an arbovirus belonging to Bunyavirales, an order of negative-stranded, enveloped RNA viruses. The virus can be transmitted to humans by the bite of an infected sandfly of the genus Phlebotomus. Toscana is not normally associated with disease, as indicated by high seroprevalence rates in endemic areas, but in common with other sandfly transmitted viruses such as Naples virus and Sicilian virus, infection may result in Pappataci fever, an illness with mild fever, headache and myalgia. In serious cases that go undiagnosed, acute meningitis, meningoencephalitis and encephalitis may occur. There is no specific treatment for infection, so treatment is supportive, reducing the severity of symptoms until the immune system has cleared the infection.

<i>Zika virus</i> Species of flavivirus

Zika virus is a member of the virus family Flaviviridae. It is spread by daytime-active Aedes mosquitoes, such as A. aegypti and A. albopictus. Its name comes from the Ziika Forest of Uganda, where the virus was first isolated in 1947. Zika virus shares a genus with the dengue, yellow fever, Japanese encephalitis, and West Nile viruses. Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia. From 2007 to 2016, the virus spread eastward, across the Pacific Ocean to the Americas, leading to the 2015–2016 Zika virus epidemic.

Mayaro virus disease is a mosquito-borne zoonotic pathogen endemic to certain humid forests of tropical South America. Infection with Mayaro virus causes an acute, self-limited dengue-like illness of 3–5 days' duration. The causative virus, abbreviated MAYV, is in the family Togaviridae, and genus Alphavirus. It is closely related to other alphaviruses that produce a dengue-like illness accompanied by long-lasting arthralgia. It is only known to circulate in tropical South America.

<i>Schmallenberg orthobunyavirus</i> Species of virus

Schmallenberg orthobunyavirus, also called Schmallenberg virus, abbreviated SBV, is a virus that causes congenital malformations and stillbirths in cattle, sheep, goats, and possibly alpaca. It appears to be transmitted by midges, which are likely to have been most active in causing the infection in the Northern Hemisphere summer and autumn of 2011, with animals subsequently giving birth from late 2011. Schmallenberg virus falls in the Simbu serogroup of orthobunyaviruses. It is considered to be most closely related to the Sathuperi and Douglas viruses.

Tahyna orthobunyavirus ("TAHV") is a viral pathogen of humans classified in the California encephalitis virus (CEV) serogroup of the Orthobunyavirus family in the order Bunyavirales, which is endemic to Europe, Asia, Africa and possibly China.

Batai orthobunyavirus (BATV) is a RNA virus belonging to order Bunyavirales, genus Orthobunyavirus.

Cache Valley orthobunyavirus (CVV) is a member of the order Bunyavirales, genus Orthobunyavirus, and serogroup Bunyamwera, which was first isolated in 1956 from Culiseta inornata mosquitos collected in Utah's Cache Valley. CVV is an enveloped arbovirus, nominally 80–120 nm in diameter, whose genome is composed of three single-stranded, negative-sense RNA segments. The large segment of related bunyaviruses is approximately 6800 bases in length and encodes a probable viral polymerase. The middle CVV segment has a 4463-nucleotide sequence and the smallest segment encodes for the nucleocapsid, and a second non-structural protein. CVV has been known to cause outbreaks of spontaneous abortion and congenital malformations in ruminants such as sheep and cattle. CVV rarely infects humans, but when they are infected it has caused encephalitis and multiorgan failure.

Jamestown Canyon encephalitis is an infectious disease caused by the Jamestown Canyon virus, an orthobunyavirus of the California serogroup. It is mainly spread during the summer by different mosquito species in the United States and Canada.

References

  1. 1 2 3 4 Nunes MRT (2005). "Oropouche Virus Isolation, Southeast Brazil". Emerging Infectious Diseases. 11 (10): 1610–1613. doi:10.3201/eid1110.050464. PMC   3366749 . PMID   16318707.
  2. ↑ "Le virus Oropouche" . Retrieved 2009-03-20.
  3. 1 2 3 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.
  4. 1 2 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 – via AJTMH.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 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.
  6. 1 2 3 4 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.
  7. 1 2 3 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.
  8. 1 2 3 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.
  9. ↑ 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.
  10. ↑ "What Is the Brain Parenchyma? (with pictures)". wiseGEEK. Retrieved 2017-12-12.
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