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{{Infobox medical condition |
{{Infobox medical condition
Name = Oropouche fever |
| Name = Oropouche fever
ICD10 = {{ICD10|A|93|0|a|90}} |
ICD9 = {{ICD9|065}} |
| ICD10 = {{ICD10|A|93|0|a|90}}
| ICD9 = {{ICD9|065}}|
}}
}}
{{Taxobox
{{Taxobox
| image = 06-1114-F1
| virus_group = v
| image_caption =
| familia = '''''Bunyaviridae'''''
| familia = '''''Bunyaviridae'''''
| genus = ''[[Orthobunyavirus]]''
| genus = ''[[Orthobunyavirus]]''
| virus_group = v
}}
}}
[[File:Anopheles stephensi.jpeg|thumb|Mosquitoes is how the oropouche virus can transfer there infection from host to host causing Oropouche Fever in humans]]
'''Oropouche fever''' is a [[tropical diseases|tropical]] [[viral infection]], a [[zoonosis]] similar to [[dengue fever]], transmitted by biting [[midge]] (species ''[[Culicoides paraensis]]'') and [[mosquito]]es from the [[blood]] of [[sloth]]s to [[human]]s. It occurs mainly in the [[Amazon Basin|Amazonic]] region, the [[Caribbean]] and [[Panama]]. The disease is named after the region where it was first described and isolated at the [[Trinidad Regional Virus Laboratory]], in 1955, the [[Oropouche River]] in [[Trinidad and Tobago]] and is caused by a specific [[arbovirus]], the [[Oropouche Virus (Bunyaviridae Orthobunyavirus)|Oropouche virus]] (OROV), of the [[Bunyaviridae]] family.
'''Oropouche fever''' is a [[Tropical diseases|tropical]] [[viral infection]] transmitted by biting [[midge]]<nowiki/>s and [[Mosquito|mosquitoes]] from the [[blood]] of [[Sloth|sloths]] to [[human]]s. 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]].<ref name="Nunes et al 2005">Nunes MRT, Martins LC, Rodrigues SG, Chiang JO, Azevedo RSS, Travassos da Rosa APA, and da Costa Vasconcelos PF. Emergence and first isolation of Oropouche virus, southeast Brazil. ''Emerging Infectious Diseases'' [serial on the Internet]. 2005 Oct. https://dx.doi.org/10.3201/eid1110.050464. DOI: 10.3201/eid1110.050464.</ref> Oropouche fever is caused by a specific [[arbovirus]], the [[Oropouche Virus (Bunyaviridae Orthobunyavirus)|Oropouche virus]] (OROV), of the [[Bunyaviridae]] family.


Large [[Epidemy|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.<ref name="urlLe virus Oropouche">{{cite web|url=http://www.mpl.ird.fr/suds-en-ligne/fr/virales/emergenc/anthr09A.htm|title=Le virus Oropouche|work=|accessdate=2009-03-20}}</ref> 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 conviction with other similar mosquito borne viruses.<ref name=":3" />
==History==
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|Coquillettidia venezuelensis]]'' [[mosquito]]es.<ref name="Nunes et al 2005">Nunes MRT, Martins LC, Rodrigues SG, Chiang JO, Azevedo RSS, Travassos da Rosa APA, and da Costa Vasconcelos PF. Emergence and first isolation of Oropouche virus, southeast Brazil. ''Emerging Infectious Diseases'' [serial on the Internet]. 2005 Oct. https://dx.doi.org/10.3201/eid1110.050464. DOI: 10.3201/eid1110.050464.</ref> In Brazil, OROV was first described in 1960 when it was isolated from a [[three-toed sloth]] (''[[Bradypus tridactylus]]'') and ''[[Ochlerotatus serratus]]'' [[mosquito]]es captured nearby during the construction of the [[Belém-Brasilia Highway]].<ref name="Nunes et al 2005">Nunes MRT, Martins LC, Rodrigues SG, Chiang JO, Azevedo RSS, Travassos da Rosa APA, and da Costa Vasconcelos PF. Emergence and first isolation of Oropouche virus, southeast Brazil. ''Emerging Infectious Diseases'' [serial on the Internet]. 2005 Oct. https://dx.doi.org/10.3201/eid1110.050464. DOI: 10.3201/eid1110.050464.</ref>


==Mechanism ==
According to Nunes et al. (2005), "the OROV [[genome]] consists of 3 partite, single-stranded, negative-sense [[RNA]]s, named large (L), medium (M), and small (S) RNA. These RNAs are predicted to encode a large [[protein]] (L: [[polymerase]] activity), viral surface [[glycoprotein]]s (Gc and Gn), and nonstructural [[NSM protein]], as well as both [[nucleocapsid]] (N) and [[NSS protein]]s. Complete [[nucleotide]] sequences have been determined for all 3 RNA segments, and previous studies of the [[molecular biology]] of the N gene (SRNA) of 28 different OROV [[Strain (biology)|strains]] indicated the existence of 3 [[genotype]]s, designated I, II, and III."<ref>{{cite journal |vauthors=Nunes MR, Martins LC, Rodrigues SG, etal |title=Oropouche virus isolation, southeast Brazil |journal=Emerging Infect. Dis. |volume=11 |issue=10 |pages=1610–3 |date=October 2005 |pmid=16318707 |doi= 10.3201/eid1110.050464|url= |pmc=3366749}}</ref>
Oropouche fever is caused by the [[oropouche virus]] (OROV) that belongs to the [[Bunyavirales|bunyaviridae]] family of arboviruses.<ref name=":0">{{Cite journal|last=Travassos da Rosa|first=Jorge Fernando|last2=de Souza|first2=William Marciel|last3=Pinheiro|first3=Francisco de Paula|last4=Figueiredo|first4=Mário Luiz|last5=Cardoso|first5=Jedson Ferreira|last6=Acrani|first6=Gustavo Olszanski|last7=Nunes|first7=Márcio Roberto Teixeira|date=2017-05-03|title=Oropouche Virus: Clinical, Epidemiological, and Molecular Aspects of a Neglected Orthobunyavirus|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417190/|journal=The American Journal of Tropical Medicine and Hygiene|volume=96|issue=5|pages=1019–1030|doi=10.4269/ajtmh.16-0672|issn=0002-9637|pmc=PMC5417190|pmid=28167595}}</ref> This virus is a single-stranded, negative sense [[RNA virus]] which is the cause of this disease. <ref name=":1">{{Cite journal|last=Vasconcelos|first=Helena B.|last2=Azevedo|first2=Raimunda S. S.|last3=Casseb|first3=Samir M.|last4=Nunes-Neto|first4=Joaquim P.|last5=Chiang|first5=Jannifer O.|last6=Cantuária|first6=Patrick C.|last7=Segura|first7=Maria N. O.|last8=Martins|first8=Lívia C.|last9=Monteiro|first9=Hamilton A. O.|date=2009-02-01|title=Oropouche fever epidemic in Northern Brazil: Epidemiology and molecular characterization of isolates|url=http://www.journalofclinicalvirology.com/article/S1386-6532(08)00399-5/fulltext|journal=Journal of Clinical Virology|language=English|volume=44|issue=2|pages=129–133|doi=10.1016/j.jcv.2008.11.006|issn=1386-6532|pmid=19117799}}</ref> There are no specific [[Ultrastructure|ultrastructural]] studies of the oropouche virus in human tissues that have been recorded to this date.<ref name=":0" /> It is likely that this viral agent shares similar morphological characteristics with other members of the [[Orthobunyavirus]] genus.<ref name=":0" /> Members of the [[Orthobunyavirus]] genus have a three part, single-stranded, negative sense [[RNA|RNA genome]] of small (S), medium (M) and large (L) RNA segments.<ref name=":0" /> These segments function to encode [[Capsid|nucleocapsids]], [[Glycoprotein|glycoproteins]] and the RNA polymerase in that sequential order.<ref name=":0" /> Through [[Phylogenetics|phylogenetic analysis]] of nucleocapsid genes in different oropouche virus strains, it has been revealed that there are three unique [[Genotype|genotypes]] (I, II, III) that are currently spreading through Central and South America.<ref name=":0" />


== Symptoms and Signs ==
=== Genomic Reassortment ===
Genetic [[Reassortment|reassortmen]]<nowiki/>t is said to be one of the most important mechanisms in explaining the viral [[biodiversity]] in orthobunyaviruses.<ref name=":0" /> This occurs when two genetically related viruses infect the same cell at the same time forming a [[Progeny (genetic descendant)|progeny]] virus and this virus holds various components of genetic L, M and S segments from the two parental viruses.<ref name=":0" /> 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.<ref name=":0" /> 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.<ref name=":0" />
It typically takes 3 to 8 days from the incubation period to first noticing signs of [[infection]]. This begins from the bite of the infected mosquito or midge and though 8 days is typically around the time signs are recognized it can also take up to 12 days in extreme cases.


=== Symptoms ===
=== 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 [[B symptoms|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.<ref name=":0" /> To further understand the pathogenesis of how this virus manifests in the body experimental studies using [[Murinae|murine]] models have been performed.
*Fever - most common and can go as high as {{convert|104|F|C|1|link-on|abbr=on}}
*Severe headaches
*Neck and back pain
*Joint pain
*Extreme sensitivity to light
*Bronchitis
*Nausea
*Diarrhoea
*Abdominal pain
*Burning sensation all over body


==== Murine Models ====
==Epidemiology==
BALB/c neonate mice were treated with this virus [[Subcutaneous tissue|subcutaneously]] and presented clinical symptoms five days after [[inoculation]].<ref name=":0" /> The mice reveled a high concentration of the replicating virus in the brain along with inflammation of the [[meninges]] and [[apoptosis]] of neurons without encephalitis<ref name=":0" />, which is inflammation of the brain due to an infection.<ref name=":0" /> These findings confirmed the neurotropism of this virus, which means that this virus is capable of infecting nerve cells. [[Immunohistochemistry test|Immunohistochemistry]] was used to reveal how this virus had access to the central nervous system.<ref name=":0" /> The findings indicated that the OROV infection starts from the posterior parts of the brain and progresses toward the forebrain.<ref name=":0" /> 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.<ref name=":0" /> As the infection progresses, the virus crosses the blood-brain barrier and spreads to the brain [[parenchyma]] leading to severe manifestations of [[encephalitis]].<ref name=":0" /> Damage to the brain parenchyma can result in the loss of cognitive ability or death.<ref>{{Cite news|url=http://www.wisegeek.org/what-is-the-brain-parenchyma.htm|title=What Is the Brain Parenchyma? (with pictures)|work=wiseGEEK|access-date=2017-12-12}}</ref>
Large [[epidemy|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.<ref name="urlLe virus Oropouche">{{cite web |url=http://www.mpl.ird.fr/suds-en-ligne/fr/virales/emergenc/anthr09A.htm |title=Le virus Oropouche |work= |accessdate=2009-03-20}}</ref> Presently, in Brazil alone it is estimated that more than half a million cases have occurred. Caveat: 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 coinfection with other similar mosquito borne viruses, we simply do not know. What we do know is Brazil's mosquito-borne viral burden is immense and diverse.


==Presentation==
== Symptoms ==
Oropouche fever is characterized as a acute febrile illness, meaning that it begins with a sudden onset of a fever followed by severe clinical symptoms.<ref name=":4">{{Cite journal|last=Pinheiro|first=F.P|last2=Travassos Da Rosa|first2=Amelia P|date=January 1981|title=Oropouche virus. I. A review of clinical, epidemiológical, and ecological findings.|url=https://www.cabdirect.org/cabdirect/abstract/19822902981|journal=American Journal of Tropical Medicine and Hygiene|volume=30|pages=149 - 160|via=AJTMH}}</ref> It typically takes 4 to 8 days from the [[Incubation period|incubation]] period to first start noticing signs of [[infection]], beginning from the bite of the infected mosquito or midge.<ref name=":0" />
Oropouche fever has an abrupt onset fever, initially with generic [[symptoms]] similar to those seen in dengue fever. such as [[Chills|chill]]s, [[headache]], [[anorexia (symptom)|anorexia]], [[muscle pain]] and [[joint pain]] and [[vomiting]]. Patients may develop symptoms of [[meningitis]]. Diagnosis is achieved by dosing the serum levels of the specific [[antibody]] to the virus.


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|epigastric]] pain, and rashes.<ref name=":1" />
==Treatment and prognosis==
The illness has no specific therapy, but usually [[symptomatic treatment]] is introduced, by using certain oral [[analgesic]] and anti-inflammatory agents, which should be prescribed by a [[physician]], because some of them (such as [[aspirin]]) are dangerous because they reduce [[blood clotting]] activity and may aggravate the hemorrhagic effects;


There also have been some cases where rashes resembles rubella and patients presented systematic symptoms including [[nausea]], [[vomiting]], [[diarrhea]], conjunctive [[Congestion of the Lungs|congestion]], [[Epigastrium|epigastric]] pain, and retro-orbitial pain.<ref name=":0" />
The infection is usually self-limiting and complications are rare. Patients usually recover fully with no long term ill effects.


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.<ref name=":0" /> Studies have shown this typically happens in about 60% of cases.<ref name=":0" />
Treatments consist of drinking lots of fluids to prevent dehydration.


== Diagnosis ==
Headaches and body pain are treated by taking analgesics. Asprin is not a recommended choice of drug because it can cause hamper blood clotting and effect the recovery time.
Diagnosis of the oropouche infection is done through classic and molecular [[virology]] techniques.<ref name=":0" /> These include:

# Virus isolation attempt in new born mice and cell culture (Vero Cells)<ref name=":0" />
Extreme causes of Oropouche fever, the drug [[Ribavirin]] is recommended to help against the virus. This is called antiviral therapy.
# Serological assay methods, such as HI ([[hemagglutination inhibition]]), NT (neutralization test), and CF ([[complement fixation test]]) tests and in-house-enzyme linked [[Immunosorbent assay|immunosorbent]] assay for total [[immunoglobulin]], IgM, and IgG detection using [[Convalescence|convalescent]] sera<ref name=":0" /><ref name=":2">{{Cite journal|last=Saeed|first=Mohammad F.|last2=Nunes|first2=Marcio|last3=Vasconcelos|first3=Pedro F.|last4=Travassos Da Rosa|first4=Amelia P. A.|last5=Watts|first5=Douglas M.|last6=Russell|first6=Kevin|last7=Shope|first7=Robert E.|last8=Tesh|first8=Robert B.|last9=Barrett|first9=Alan D. T.|date=2001-7|title=Diagnosis of Oropouche Virus Infection Using a Recombinant Nucleocapsid Protein-Based Enzyme Immunoassay|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88168/|journal=Journal of Clinical Microbiology|volume=39|issue=7|pages=2445–2452|doi=10.1128/JCM.39.7.2445-2452.2001|issn=0095-1137|pmid=11427552}}</ref> (this obtained from recovered patients and is rich in antibodies against the infectious agent)
# [[Reverse transcription polymerase chain reaction|Reverse transcription polymerase]] chain reaction (RT-PCR) and real time RT-PCR for genome detection in acute samples (sera, blood, and [[Organ (anatomy)|viscera]] of infected animals)<ref name=":0" />
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.<ref name=":2" />


== Cause and Prevention ==
== Cause and Prevention ==
<nowiki/>The oropouche virus is an emerging [[Infection|infectious]] agent that causes the illness oropouche fever.<ref name=":2" /> This virus is an arbovirus and is transmitted among sloths, marsupials, primates, and birds through the mosquitoes [[Aedes|Aedes serratus]] and [[Culex quinquefasciatus|Culex quinquefaciatus]].<ref name=":3">{{Cite journal|last=Mourão|first=Maria Paula G.|last2=Bastos|first2=Michelle S.|last3=Gimaque|first3=João Bosco L.|last4=Mota|first4=Bruno Rafaelle|last5=Souza|first5=Giselle S.|last6=Grimmer|first6=Gustavo Henrique N.|last7=Galusso|first7=Elizabeth S.|last8=Arruda|first8=Eurico|last9=Figueiredo|first9=Luiz Tadeu M.|date=2009-12|title=Oropouche Fever Outbreak, Manaus, Brazil, 2007–2008|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044544/|journal=Emerging Infectious Diseases|volume=15|issue=12|pages=2063–2064|doi=10.3201/eid1512.090917|issn=1080-6040|pmc=PMC3044544|pmid=19961705}}</ref> The oropouche virus has evolved to an urban cycle infecting humans though [[Midge|midges]] as its main transporting vector.<ref name=":3" />
Oropouche fever is present in epidemics so the chances of one contracting it after being exposed to areas of midgets or mosquitoes is rare.

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|Coquillettidia venezuelensis]]'' [[Mosquito|mosquitoes]].<ref name="Nunes et al 2005" /> In Brazil, OROV was first described in 1960 when it was isolated from a [[three-toed sloth]] (''[[Bradypus tridactylus]]'') and ''[[Ochlerotatus serratus]]'' [[Mosquito|mosquitoes]] captured nearby during the construction of the [[Belém-Brasilia Highway]].<ref name="Nunes et al 2005" /> The oropouche virus is responsible for causing massive, explosive outbreaks in in Latin American countries, making oropouche fever the second most common arboviral infection seen in Brazil.<ref>{{Cite journal|last=Bastos|first=Michele de Souza|last2=Figueiredo|first2=Luiz Tadeu Moraes|last3=Naveca|first3=Felipe Gomes|last4=Monte|first4=Rossicleia Lins|last5=Lessa|first5=Natália|last6=Pinto de Figueiredo|first6=Regina Maria|last7=Gimaque|first7=João Bosco de Lima|last8=Pivoto João|first8=Guilherme|last9=Ramasawmy|first9=Rajendranath|date=2012-04-01|title=Short Report: Identification of Oropouche Orthobunyavirus in the Cerebrospinal Fluid of Three Patients in the Amazonas, Brazil|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403753/|journal=The American Journal of Tropical Medicine and Hygiene|volume=86|issue=4|pages=732–735|doi=10.4269/ajtmh.2012.11-0485|issn=0002-9637|pmc=PMC3403753|pmid=22492162}}</ref> So far the only reported cases of Oropouche fever have been in Brazil, Panama, Peru, and Trinidad and Tobago.<ref name=":0" />

ORO fever occurs mainly during the rainy seasons because there is an increase in [[breeding]] sites in the vector populations.<ref name=":0" /> 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.<ref name=":0" /> 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.<ref name=":0" />


=== Prevention ===
=== Prevention ===
By 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.
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.<ref name=":1" />


Oropouche fever is present in epidemics so the chances of one contracting it after being exposed to areas of midgets or mosquitoes is rare.<ref name=":1" />
==Footnotes==

{{Reflist}}
==Treatment and Prognosis==
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 (journal)|antiviral '''therapy''']]. Treatments also consist of drinking lots of fluids to prevent dehydration.

Asprin is not a recommended choice of drug because it can reduce blood clotting and may aggravate the hemorrhagic effects and prolong recovery time.

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.<ref name="Nunes et al 2005" /> Patients usually recover fully with no long term ill effects. There have been no recorded fatalities resulting from oropouche fever.<ref name=":4" />

== Recent Research ==
One study has focused on identifying OROV through the use of RNA extraction from reverse transcription-polymerase chain reaction.<ref name=":5">{{Cite journal|last=Bastos|first=Michele de Souza|last2=Figueiredo|first2=Luiz Tadeu Moraes|last3=Naveca|first3=Felipe Gomes|last4=Monte|first4=Rossicleia Lins|last5=Lessa|first5=Natália|last6=Pinto de Figueiredo|first6=Regina Maria|last7=Gimaque|first7=João Bosco de Lima|last8=Pivoto João|first8=Guilherme|last9=Ramasawmy|first9=Rajendranath|date=2012-04-01|title=Short Report: Identification of Oropouche Orthobunyavirus in the Cerebrospinal Fluid of Three Patients in the Amazonas, Brazil|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403753/|journal=The American Journal of Tropical Medicine and Hygiene|volume=86|issue=4|pages=732–735|doi=10.4269/ajtmh.2012.11-0485|issn=0002-9637|pmc=PMC3403753|pmid=22492162}}</ref> 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 glucose|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 pervious blood-brain barrier damage.<ref name=":5" />


==References==
==References==
{{Reflist}}
* {{cite journal |vauthors=Anderson CR, Spence L, Downs WG, Aitken TH |title=Oropouche virus: a new human disease agent from Trinidad, West Indies |journal=Am. J. Trop. Med. Hyg. |volume=10 |issue= |pages=574–8 |date=July 1961 |pmid=13683183 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=13683183}}

* {{cite journal |vauthors=Saeed MF, Wang H, Nunes M, etal |title=Nucleotide sequences and phylogeny of the nucleocapsid gene of Oropouche virus |journal=J. Gen. Virol. |volume=81 |issue=Pt 3 |pages=743–8 |date=March 2000 |pmid=10675412 |doi= |url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=10675412}}
<ul><li> </li></ul>


==External links==
==External links==
* [http://www.medicdirect.co.uk/clinics/default.ihtml?step=4&pid=2238 Oropouche fever]. MedicDirect.
<ul><li href=":Category:CS1 maint: Multiple names: authors list"> [http://www.medicdirect.co.uk/clinics/default.ihtml?step=4&pid=2238 Oropouche fever]. MedicDirect.</li>
* [http://www.fmrp.usp.br/revista/1999/vol32n2/virus_brasileiros_familia_bunyaviridae.pdf Brazilian Viruses of the Bunyaviridae Family]. Medicina Ribeirão (in Portuguese)
<li> [http://www.fmrp.usp.br/revista/1999/vol32n2/virus_brasileiros_familia_bunyaviridae.pdf Brazilian Viruses of the Bunyaviridae Family]. Medicina Ribeirão (in Portuguese)</li></ul>


{{Zoonotic viral diseases}}
{{Zoonotic viral diseases}}


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Revision as of 06:40, 13 December 2017

Oropouche fever
SpecialtyInfectious diseases Edit this on Wikidata

Oropouche fever
File:06-1114-F1
Virus classification
Group:
Group V ((−)ssRNA)
Family:
Bunyaviridae
Genus:
Mosquitoes is how the oropouche virus can transfer there infection from host to host causing Oropouche Fever in humans

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.

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 conviction with other similar mosquito borne viruses.[3]

Mechanism

Oropouche fever is caused by the oropouche virus (OROV) that belongs to the bunyaviridae family of arboviruses.[4] This virus is a single-stranded, negative sense RNA virus which is the cause of this disease. [5] There are no specific ultrastructural studies of the oropouche virus in human tissues that have been recorded to this date.[4] It is likely that this viral agent shares similar morphological characteristics with other members of the Orthobunyavirus genus.[4] 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.[4] These segments function to encode nucleocapsids, glycoproteins and the RNA polymerase in that sequential order.[4] 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.[4]

Genomic Reassortment

Genetic reassortment is said to be one of the most important mechanisms in explaining the viral biodiversity in orthobunyaviruses.[4] 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.[4] 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.[4] 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.[4]

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.[4] To further understand the pathogenesis of how this virus manifests in the body experimental studies using murine models have been performed.

Murine Models

BALB/c neonate mice were treated with this virus subcutaneously and presented clinical symptoms five days after inoculation.[4] The mice reveled a high concentration of the replicating virus in the brain along with inflammation of the meninges and apoptosis of neurons without encephalitis[4], which is inflammation of the brain due to an infection.[4] 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.[4] The findings indicated that the OROV infection starts from the posterior parts of the brain and progresses toward the forebrain.[4] 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.[4] As the infection progresses, the virus crosses the blood-brain barrier and spreads to the brain parenchyma leading to severe manifestations of encephalitis.[4] Damage to the brain parenchyma can result in the loss of cognitive ability or death.[6]

Symptoms

Oropouche fever is characterized as a acute febrile illness, meaning that it begins with a sudden onset of a fever followed by severe clinical symptoms.[7] 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.[4]

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.[5]

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.[4]

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.[4] Studies have shown this typically happens in about 60% of cases.[4]

Diagnosis

Diagnosis of the oropouche infection is done through classic and molecular virology techniques.[4] These include:

  1. Virus isolation attempt in new born mice and cell culture (Vero Cells)[4]
  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[4][8] (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)[4]

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.[8]

Cause and Prevention

The oropouche virus is an emerging infectious agent that causes the illness oropouche fever.[8] 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 in Latin American countries, making oropouche fever the second most common arboviral infection seen in Brazil.[9] So far the only reported cases of Oropouche fever have been in Brazil, Panama, Peru, and Trinidad and Tobago.[4]

ORO fever occurs mainly during the rainy seasons because there is an increase in breeding sites in the vector populations.[4] 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.[4] 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.[4]

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.[5]

Oropouche fever is present in epidemics so the chances of one contracting it after being exposed to areas of midgets or mosquitoes is rare.[5]

Treatment and Prognosis

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 lots of fluids to prevent dehydration.

Asprin is not a recommended choice of drug because it can reduce blood clotting and may aggravate the hemorrhagic effects and prolong recovery time.

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.[7]

Recent Research

One study has focused on identifying OROV through the use of RNA extraction from reverse transcription-polymerase chain reaction.[10] 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 pervious blood-brain barrier damage.[10]

References

  1. ^ a b c d Nunes MRT, Martins LC, Rodrigues SG, Chiang JO, Azevedo RSS, Travassos da Rosa APA, and da Costa Vasconcelos PF. Emergence and first isolation of Oropouche virus, southeast Brazil. Emerging Infectious Diseases [serial on the Internet]. 2005 Oct. https://dx.doi.org/10.3201/eid1110.050464. DOI: 10.3201/eid1110.050464.
  2. ^ "Le virus Oropouche". Retrieved 2009-03-20.
  3. ^ a b c 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. (2009-12). "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. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad 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.{{cite journal}}: CS1 maint: PMC format (link)
  5. ^ a b c d 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.
  6. ^ "What Is the Brain Parenchyma? (with pictures)". wiseGEEK. Retrieved 2017-12-12.
  7. ^ a b 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: 149–160 – via AJTMH.
  8. ^ a b c 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. (2001-7). "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. PMID 11427552. {{cite journal}}: Check date values in: |date= (help)
  9. ^ 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.{{cite journal}}: CS1 maint: PMC format (link)
  10. ^ a b 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.{{cite journal}}: CS1 maint: PMC format (link)

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