SHORT COMMUNICATION ARTICLE Dipankar et.al / UJPSR / 3 (2), 2017, 33-37 Department of Pharmacy e ISSN: 2454-3764 Print ISSN: 2454-3756 DOI: 10.21276/UJPSR.2017.03.02.93

OROPOUCHE: A NEW HEADACHE FOR MEDICAL SCIENCE

Dipankar Kumar Bhagat*, Sourav Mohanto, Dr. Shubhrajit Mantry

Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar, Sikkim, INDIA

ARTICLE INFO: Abstract Article history: Oropouche virus (OROV) is an important cause of arboviral Received: illness in Latin American countries, more specifically in the 19 August 2017 Amazon region of Brazil, Venezuela and Peru, as well as in Received in revised form: other countries such as Panama. In the past decades, the 05 September 2017 clinical, epidemiological, pathological, and molecular aspects Accepted: 12 November 2017 of OROV have been published and provide the basis for a better understanding of this important human pathogen. Here, Available online: 10 December 2017 we describe the milestones in a comprehensive review of

OROV epidemiology, pathogenesis, and molecular biology, Corresponding Author: including a description of the first isolation of the virus, the

Dipankar Kumar Bhagat outbreaks during the past six decades, clinical aspects of OROV infection, diagnostic methods, genome and genetic Himalayan Pharmacy Institute traits, evolution, and viral dispersal.

Majhitar, Sikkim, 737136, INDIA Key words Email: [email protected] OROV, Human Pathogen, Panama Phone: +91-7319556801

INTRODUCTION Oropouche virus (OROV) is one of the most is the causative agent of Oropouche fever, a febrile common arboviruses that infect humans in Brazil. arboviral illness that is frequently associated with It is estimated that since the first isolation of the the Brazilian–Amazon region. The virus was first virus in 1955, it has affected more than half a isolated in Brazil in 1960 from the blood of a million people. However, the exact number of sloth, Bradypus trydactilus, captured in a forested cases is difficult to determine, because the infection area during the construction of the Belém-Brasilia is underreported due to the similarity of symptoms highway and also from a pool of Ochlerotatus with other arboviral febrile illnesses, such as serratus mosquitoes caught near the same area Dengue, Zika, Chikungunya, and Mayaro fevers. [1,2]. The lack of an exact diagnosis in hospitals and Taxonomy and Classification health-care centers hinders the proper OROV is a member of the family Bunyaviridae, epidemiological notification, which is the principal genus Orthobunyavirus, the largest genus of RNA reason why the estimated number of cases is lower viruses with over 170 named viruses corresponding than what is probably occurring in the population, to 18 different serogroups and 48 species especially in the Amazon-endemic region. OROV complexes. The OROV classification was

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SHORT COMMUNICATION ARTICLE Dipankar et.al / UJPSR / 3 (2), 2017, 33-37 Department of Pharmacy e ISSN: 2454-3764 DOI: 10.21276/UJPSR.2017.03.02.93 Print ISSN: 2454-3756 originally made using serological methods, such as 1985. OROV replicates in numerous cell cultures, CF, hemagglutination inhibition (HI), or including C6/36, Vero, BHK-21, MA III, LCM- neutralizing (NT) tests. Currently, the Simbu MK2, and primary chicken embryo fibroblasts, serogroup is composed by two phylogenetic causing a cytopathic effect from subtotal to total subclades: subclade A, which includes Oropouche destruction of the cell monolayer, depending on the and Manzanilla orthobunyaviruses, and subclade B, multiplicity of infection used and time constituted by Simbu, Shuni, Shamonda, Sathuperi, postinfection. OROV is sensitive to sodium and Akabane viruses. Hemagglutinin antigens can deoxycholate, which reduces the ability of the virus be prepared to OROV from brain and serum to infect the host cells by destroying the envelope samples of infected hamsters, which have been glycoprotein, a viral structure that is directly used in epidemiological surveillance for precise associated with virus–host interaction [2]. serological diagnostic of OROV infections since

Fig.1: Ochlerotatus serratus mosquitoes Geographical Distribution of OROV Thus far, the only reported cases of Oropouche and Peru. The outbreak in Panama was recorded in (ORO) fever have occurred in Brazil, Panama, 1989 in the Village of Bejuco, located Peru, and Trinidad and Tobago. In Brazil, since the approximately 50 km west of Panama City, capital first isolation of the virus in 1955 until 1980, of the country. In Peru, ORO fever was OROV caused several epidemics apparently documented in 1992, when the virus caused an restricted to the State of Pará, northern Brazil, outbreak in Iquitos City. Furthermore, two other reaching different municipalities of distinct outbreaks of OROV were recorded in the Peruvian mesoregions: metropolitan area of Belém, Amazon in 1994, in the cities of Puerto Maldonado northeast, southeast, lowers Amazon etc. Outside and Madre de Dios [1]. of Brazil, epidemics have been reported in Panama 34 | P a g e

SHORT COMMUNICATION ARTICLE Dipankar et.al / UJPSR / 3 (2), 2017, 33-37 Department of Pharmacy e ISSN: 2454-3764 DOI: 10.21276/UJPSR.2017.03.02.93 Print ISSN: 2454-3756

Fig.2: Geographical Distribution of OROV

Transmission Cycles Studies conducted by the Evandro Chagas Institute maintenance of the urban cycle. Humans are suggest that OROV is maintained in nature by two probably also the link between the sylvatic and distinct cycles: sylvatic and urban. In the sylvatic urban cycles, when humans invade the forest, cycle, there is evidence that pale-throated sloths become infected, and return to urban areas during (Bradypus tridactylus), nonhuman primates and the viremic period. Two vectors are commonly some wild birds play a role as vertebrate hosts. The found in urban epidemics: the biting vector of OROV in the forest is still unclear. On midge Culicoides paraensis (Ceratopogonidae), two occasions, the agent has been isolated from regionally named as “maruim,” and the sylvatic mosquitoes, both in 1960. One isolation mosquito Culex p. quinquefasciatus (Culicidae). In was from O. serratus collected in the Amazon laboratory experiments with the Culex p. region of Brazil, and the second was quinquefasciatus, the insect proved to be an from Coquilletidia venezuelensis in Trinidad [3]. In inefficient vector of OROV. Furthermore, Cardoso the urban or epidemic cycle, humans apparently are and others detected the SRNA of OROV in patients the only vertebrates involved, since studies with and in Culex quinquefasciatus, reinforcing the domestic animals (e.g., dogs, cats, and chickens) probable participation of Culex mosquitoes in the excluded the role of these animals in the urban cycle of OROV [4].

Fig.3: Transmission Cycles of Oropouche virus 35 | P a g e

SHORT COMMUNICATION ARTICLE Dipankar et.al / UJPSR / 3 (2), 2017, 33-37 Department of Pharmacy e ISSN: 2454-3764 DOI: 10.21276/UJPSR.2017.03.02.93 Print ISSN: 2454-3756 Signs and Symptoms After the infected mosquito bite, the incubation diagnosis for other common arboviral diseases period or the time when one sees the first signs of (e.g., chikungunya, dengue, yellow fever, infection, is typically around 3- 8 days although it Zika virus).The proximity of midge vector breeding could be as late as 12 days. Fever is most common to human habitation is a significant risk factor for with high-grade temperatures often up to 104o F Oropouche virus infection. Prevention and control accompanied by severe headaches, body ache, and relies on reducing the breeding of midges through extreme sensitivity to light. This also may be source reduction (removal and modification of accompanied by nausea, diarrhoea, abdominal breeding sites) and reducing contact between cramping, bronchitis, and burning sensation - all midges and people. This can be achieved by over the body. While Oropouche fever lasts for reducing the number of natural and artificial water- about a week, recovery time is slow. Fortunately, it filled habitats that support midge larvae, reducing is not a fatal disease, except that there is a lot of the adult midge populations around at-risk distress to the affected individual [4,5]. communities and by using barriers such as insect Causes and prevention screens, closed doors and windows, long clothing The disease is caused by a virus called oropouche and repellents [7]. virus and is afflicted by the bite of mosquitoes as or FUTURE PERSPECTIVES a particular type of fly named „midge‟. Oropouche OROV is one of the most important orthobunya fever usually occurs in epidemics, so chances are viruses associated with human diseases in tropical rare that one may bring home the illness after America, with more than 30 major outbreaks and visiting one of the areas where the midge fly or the half million reported cases since its first isolation in mosquitoes live. But by checking into the area 1955. In this review, we discussed the major before leaving for the oropouche fever endemic breakthroughs achieved in OROV research. areas, one can prepare in advance. Should one need However, there are many more questions that need to travel to these areas, they should be prepared to to be addressed to fully understand the protect themselves against mosquitoes and biting epidemiology and pathogenesis of this virus. The midge flies. The liberal use of a mosquito and reverse genetics system developed for OROV insect repellent is wise as is wearing clothes which could be exploited for this purpose, which could be fully cover the body. Mosquito net is also advised used to better understand the role of the non for sleeping areas [5,6]. structural proteins during viral replication in WHO advice mosquito and mammalian cells. This reverse Given its clinical presentation, Oropouche fever genetics system could also be used to better should be included in the clinical differential understand the reassortment events in the family Bunyaviridae and its effects. Since the M segment 36 | P a g e

SHORT COMMUNICATION ARTICLE Dipankar et.al / UJPSR / 3 (2), 2017, 33-37 Department of Pharmacy e ISSN: 2454-3764 DOI: 10.21276/UJPSR.2017.03.02.93 Print ISSN: 2454-3756 is the only viral genomic segment that is different by the Oropouche virus. In humans, it is between MMDV, IQTV, and PERDV reassortants, transmitted primarily through the bite of the the system could be used to generate recombinant Culicoides Paraensis midge. No direct transmission viruses and study the differences they present in of the virus from human to human has been terms of pathogenesis, virulence outcome, and host documented. The proximity of midge vector range, which could elucidate important breeding to human habitation is a significant risk implications on the understanding of the evolution factor for Oropouche virus infection. Prevention of orthobunya viruses in South America. The virus- and control relies on reducing the breeding of like particles assay developed for this virus could midges through source reduction (removal and also be used as a tool to generate a potential modification of breeding sites) and reducing recombinant vaccine as well as a safe BSL-3 free contact between midges and people. This can be ELISA diagnosis, which could facilitate the study achieved by reducing the number of natural and of the prevalence of OROV in South America [8]. artificial water-filled habitats that support midge CONCLUSION larvae, reducing the adult midge populations In the Americas, outbreaks of Oropouche fever around at-risk communities and by using barriers virus have been reported from rural and urban such as insect screens, closed doors and windows, communities of Brazil, Ecuador, Panama, Peru, and long clothing and repellents. Trinidad and Tobago. Oropouche fever is caused REFERENCES 1. https://www.ncbi.nlm.nih.gov/pmc/articles/ 6. https://www.sciencedaily.com/releases/201 PMC5417190/ 7/08/170822111029.htm 2. https://en.wikipedia.org/wiki/Oropouche_vi 7. http://www.who.int/csr/don/03-june-2016- rus oropouche-peru/en/ 3. https://www.sciencedaily.com/releases/201 8. Tilston-Lunel NL, Acrani GO, Randall RE, 7/08/170822111029.htm 4. https://homeayurvedic.com/oropouche- Elliott RM, 2016. Generation of virus-fever-infection-overview/ recombinant Oropouche viruses lacking the 5. https://www.privatehealth.co.uk/conditions- nonstructural protein NSm or NSs. J and-treatments/oropouche-fever/symptoms/ Virol90:2616–2627.

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