Fatal Oropouche Virus Infections in Nonendemic Region, Brazil, 2024.

We report acute Oropouche virus infections in 2 previously healthy women from a nonendemic region of Brazil outside the Amazon Basin. Infections rapidly progressed to hemorrhagic manifestations and fatal outcomes in 4-5 days. These cases highlight the critical need for enhanced surveillance to clarify epidemiology of this neglected disease.

NEW RECORDS OF CULICOIDES (HAEMATOMYIDIUM) PARAENSIS AND A KEY TO ADULT CULICOIDES FROM YUCATAN PENINSULA, MEXICO.

We provide new records of Culicoides paraensis from the Yucatan Peninsula. The anthropophilic biting midge C. paraensis is the main vector of Oropouche fever virus in South and Central America. We also report Culicoides poikilonotus for the 1st time in the Yucatan Peninsula and a key to identify the species in this region of Mexico.

Oropouche fever cases diagnosed in Italy in two epidemiologically non-related travellers from Cuba, late May to early June 2024.

Oropouche fever is caused by Oropouche virus (OROV), transmitted primarily through the bite of infected midges, particularly of the genus Culicoides. The virus is mainly circulating in Central and South America where several countries reported an ongoing outbreak. We report here two imported cases of OROV infection identified in Italy, late May-early June 2024. These cases indicate that in the shadow of a massive dengue outbreak in the Americas, the Oropouche outbreak might be more widespread than previously estimated.

Influence of meteorological and seasonal parameters on the activity of Culicoides paraensis (Diptera: Ceratopogonidae), an annoying anthropophilic biting midge and putative vector of Oropouche Virus in Rondônia, Brazilian Amazon.

Biting midges of the genus Culicoides are insects of proven medical and veterinary importance, because of their role in the transmission of viruses, bacteria, protozoa and nematodes. Culicoides paraensis has been considered the main vector of the Oropouche Virus (OROV) in the urban cycle of the disease in the neotropics. Due to the great abundance of Culicoides spp. in the State of Rondônia and its epidemiological history of OROV, we investigated the biting activity in humans, the abundance as a function of meteorological parameters and seasonality, and the detection of OROV. Entomological collections occurred in three municipalities from Brazilian State of Rondônia: Porto Velho, Ariquemes, and Ouro Preto do Oeste. GLMM's were used to determine if Culicoides spp. abundance was predicted by seasonal, diurnal, and meteorological factors. Total RNA was extracted from insects and viral RNA detection was performed using the S segment as the target region of OROV via RT-qPCR. In total, 7315 individuals were captured and identified as C. paraensis. In the dry season, 1488 individuals (24.5%) were recorded, 4591 (75.5%) in the rainy season, with peaks of biting activity between 4pm and 6pm. All variables showed a significative effect on the midge abundance. The rainy season, temperature between 30 °C and 32 °C and relative air humidity between 75% and 85% were the main predictive parameters for capturing the highest average number of insects. Our results confirm diurnal activity of C. paraensis and its greatest abundance in rainy periods. No sample was positive for the OROV, which could be explained by the virus absence in local human populations, C. paraensis as a minor vector species in the sampled localities, and probable low rate of infection of biting midges. Our findings on hourly and seasonal biting activities can provide support to intervention actions regarding vector control and surveillance of this species. This was the first study to collect and analyze biting midges in a region where human OROV cases had already been detected, but without previous information on entomovirological surveillance.

Oropouche Virus Glycoprotein Topology and Cellular Requirements for Glycoprotein Secretion.

Oropouche virus (OROV; genus Orthobunyavirus) is the etiological agent of Oropouche fever, a debilitating febrile illness common in South America. We used recombinant expression of the OROV M polyprotein, which encodes the surface glycoproteins Gn and Gc plus the nonstructural protein NSm, to probe the cellular determinants for OROV assembly and budding. Gn and Gc self-assemble and are secreted independently of NSm. Mature OROV Gn has two predicted transmembrane domains that are crucial for glycoprotein translocation to the Golgi complex and glycoprotein secretion, and unlike related orthobunyaviruses, both transmembrane domains are retained during Gn maturation. Disruption of Golgi function using the drugs brefeldin A and monensin inhibits glycoprotein secretion. Infection studies have previously shown that the cellular endosomal sorting complexes required for transport (ESCRT) machinery is recruited to Golgi membranes during OROV assembly and that ESCRT activity is required for virus secretion. A dominant-negative form of the ESCRT-associated ATPase VPS4 significantly reduces recombinant OROV glycoprotein secretion and blocks virus release from infected cells, and VPS4 partly colocalizes with OROV glycoproteins and membranes costained with Golgi markers. Furthermore, immunoprecipitation and fluorescence microscopy experiments demonstrate that OROV glycoproteins interact with the ESCRT-III component CHMP6, with overexpression of a dominant-negative form of CHMP6 significantly reducing OROV glycoprotein secretion. Taken together, our data highlight differences in M polyprotein processing across orthobunyaviruses, indicate that Golgi and ESCRT function are required for glycoprotein secretion, and identify CHMP6 as an ESCRT-III component that interacts with OROV glycoproteins. IMPORTANCE Oropouche virus causes Oropouche fever, a debilitating illness common in South America that is characterized by high fever, headache, myalgia, and vomiting. The tripartite genome of this zoonotic virus is capable of reassortment, and there have been multiple epidemics of Oropouche fever in South America over the last 50 years, making Oropouche virus infection a significant threat to public health. However, the molecular characteristics of this arbovirus are poorly understood. We developed a recombinant protein expression system to investigate the cellular determinants of OROV glycoprotein maturation and secretion. We show that the proteolytic processing of the M polypeptide, which encodes the surface glycoproteins (Gn and Gc) plus a nonstructural protein (NSm), differs between OROV and its close relative Bunyamwera virus. Furthermore, we demonstrate that OROV M glycoprotein secretion requires the cellular endosomal sorting complexes required for transport (ESCRT) membrane-remodeling machinery and identify that the OROV glycoproteins interact with the ESCRT protein CHMP6.

Epidemiological aspects of the Oropouche virus (Orthobunyavirus) in South America: A systematic review

SUMMARY Introduction: The Oropouche virus (OROV) is an arbovirus that belongs to the genus Orthobunyavirus and family Peribunyaviridae, responsible for causing Oropouche fever (OF) in humans. The clinical diagnosis of is doubtful due to the non-specificity of the symptoms, which can lead to a mistaken diagnosis of other arboviruses. Thus, the survey of epidemiological data on the occurrence of has been a major challenge for public health authorities, especially in of South America. Aim: To determine the general exposure rate of OROV in Brazil and other countries in South America by a systematic review. An article search was carried out in the Pubmed/ Medline, Scopus, Cochrane, Lilacs, Electronic Scientific Online Library (SciELO) and Virtual Health Library (VHL) databases. Results: 18 studies were selected as eligible to compose this review on epidemiological aspects of OROV. The studies were published from 1989 to 2020. Most studies were carried out in Brazil (12/18; 66.66%) and Peru (5/18; 27.77%), only one study collected samples from Peru, Ecuador, Bolivia and Paraguay. The test for the OROV was realized mainly by serological analysis. Of the 8005 samples analyzed, 1570 tested positive for the presence of OROV thus accounting a general exposure rate in South America of 19.61%. Brazil was responsible for more than half of the cases of OROV identified in South America (855/1570; 54.46%), however Peru has the highest rate of exposure to the virus (23.43% of frequency in Peru vs. 16.77% of frequency in Brazil). Conclusion: OROV stands out as an important public health problem in Amazonian countries in South America.

Introdução: o virus Oropouche (OROV) é um arbovírus pertencente ao gênero Orthobunyavirus e família Peribunyaviridae, responsável por causar a febre Oropouche (FO) em humanos. O diagnóstico clínico da FO é duvidoso devido à não especificidade dos sintomas, o que pode levar a um diagnóstico equivocado de outras arboviroses. Assim, o levantamento de dados epidemiológicos sobre a ocorrência de FO tem sido um grande desafio para as autoridades de saúde pública, principalmente na América do Sul. Objetivo: determinar a taxa geral de exposição de OROV no Brasil e em outros países da América do Sul por meio de uma revisão sistemática. Foi realizada busca de artigos nas bases de dados Pubmed/ Medline, Scopus, Cochrane, Lilacs, Electronic Scientific Online Library (SciELO) e Virtual Health Library (BVS). Resultados: 18 estudos foram selecionados como elegíveis para compor esta revisão sobre aspectos epidemiológicos da OROV. Os estudos foram publicados de 1989 a 2020. A maioria dos estudos foi realizada no Brasil (18/12; 66,66%) e Peru (18/5; 27,77%), apenas um estudo coletou amostras do Peru, Equador, Bolívia e Paraguai. O teste para o OROV foi realizado principalmente por análise sorológica. Das 8005 amostras analisadas, 1570 testaram positivo para a presença de OROV, representando assim uma taxa de exposição geral na América do Sul de 19,61%. O Brasil foi responsável por mais da metade dos casos de OROV identificados na América do Sul (855/1570; 54,46%), porém o Peru tem a maior taxa de exposição ao vírus (23,43% de frequência no Peru vs. 16,77% de frequência em Brasil). Conclusão: OROV destaca-se como um importante problema de saúde pública nos países amazônicos da América do Sul.

Introducción: el virus Oropouche (OROV) es un arbovirus que pertenece al género Orthobunyavirus y familia Peribunyaviridae, responsable de causar la fiebre de oropouche (FO) en humanos. El diagnóstico clínico de FO es dudoso debido a la inespecificidad de los síntomas, lo que puede conducir a un diagnóstico erróneo de otros arbovirus. Por lo tanto, el levantamiento de datos epidemiológicos sobre la ocurrencia de FO ha sido un gran desafío para las autoridades de salud pública, especialmente en el sur de América del Sur. Objetivo: determinar la tasa de exposición general de OROV en Brasil y otros países de América del Sur mediante una revisión sistemática. Se realizó una búsqueda de artículos en las bases de datos Pubmed/ Medline, Scopus, Cochrane, Lilacs, Electronic Scientific Online Library (SciELO) y Virtual Health Library (BVS). Resultados: 18 estudios fueron seleccionados como elegibles para esta revisión sobre aspectos epidemiológicos de OROV. Los estudios se publicaron entre 1989 y 2020. La mayoría de los estudios se realizaron en Brasil (12/18; 66,66 %) y Perú (5/18; 27,77 %), solo un estudio recolectó muestras de Perú, Ecuador, Bolivia y Paraguay. La prueba para el OROV se realizó principalmente por análisis serológico. De las 8005 muestras analizadas, 1570 dieron positivo a la presencia de OROV, lo que representa una tasa de exposición general en América del Sur del 19,61 %. Brasil fue responsable de más de la mitad de los casos de OROV identificados en América del Sur (855/1570; 54,46 %), sin embargo, Perú tiene la tasa más alta de exposición al virus (23,43 % de frecuencia en Perú vs. 16,77 % de frecuencia en Brasil). Conclusión: OROV se destaca como un importante problema de salud pública en los países amazónicos de América del Sur.

Outbreak of Oropouche Virus in French Guiana.

Oropouche fever is a zoonotic dengue-like syndrome caused by Oropouche virus. In August-September 2020, dengue-like syndrome developed in 41 patients in a remote rainforest village in French Guiana. By PCR or microneutralization, 23 (82.1%) of 28 tested patients were positive for Oropouche virus, documenting its emergence in French Guiana.

Evidence of Oropouche Orthobunyavirus Infection, Colombia, 2017.

We describe an Oropouche orthobunyavirus infection in a women 28 years of age in Colombia. We confirmed the diagnosis by viral isolation, quantitative reverse transcription PCR, and phylogenetic analysis of the small, medium, and large genomic segments. The virus is related to a strain isolated in Ecuador in 2016.

Oropouche Virus-Associated Aseptic Meningoencephalitis, Southeastern Brazil.

Oropouche fever is a neglected arthropodborne disease and zoonosis responsible for several outbreaks of a febrile disease in Central and South America. We present a clinical case of aseptic meningoencephalitis in an immunocompetent patient that resulted from Oropouche virus acquired in northern Brazil but diagnosed in a nonendemic region.

Oropouche fever, an emergent disease from the Americas.

Oropouche virus is the aetiological agent of Oropouche fever, a zoonotic disease mainly transmitted by midges of the species Culicoides paraensis. Although the virus was discovered in 1955, more attention has been given recently to both the virus and the disease due to outbreaks of Oropouche fever in different areas of Brazil and Peru. Serological studies in human and wild mammals have also found Oropouche virus in Argentina, Bolivia, Colombia, and Ecuador. Several mammals act as reservoirs of the disease, although the sylvatic cycle of Oropouche virus remains to be assessed properly. Oropouche fever lacks key symptoms to be differentiated from other arboviral febrile illnesses from the Americas. Sporadic cases of aseptic meningitis have also been described with good prognosis. Habitat loss can increase the likelihood of Oropouche virus emergence in the short-term in South America.

Arboviral diseases in the Western Brazilian Amazon: a perspective and analysis from a tertiary health & research center in Manaus, State of Amazonas

The Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), located in Manaus, the capital of the State of Amazonas (Western Brazilian Amazon), is a pioneering institution in this region regarding the syndromic surveillance of acute febrile illness, including arboviral infections. Based on the data from patients at the FMT-HVD, we have detected recurrent outbreaks in Manaus by the four dengue serotypes in the past 15 years, with increasing severity of the disease. This endemicity has culminated in the simultaneous circulation of all four serotypes in 2011, the first time this has been reported in Brazil. Between 1996 and 2009, 42 cases of yellow fever (YF) were registered in the State of Amazonas, and 71.4% (30/42) were fatal. Since 2010, no cases have been reported. Because the introduction of the yellow fever virus into a large city such as Manaus, which is widely infested by Aedes mosquitoes, may pose a real risk of a yellow fever outbreak, efforts to maintain an appropriate immunization policy for the populace are critical. Manaus has also suffered silent outbreaks of Mayaro and Oropouche fevers lately, most of which were misdiagnosed as dengue fever. The tropical conditions of the State of Amazonas favor the existence of other arboviruses capable of producing human disease. Under this real threat, represented by at least 4 arboviruses producing human infections in Manaus and in other neighboring countries, it is important to develop an efficient public health surveillance strategy, including laboratories that are able to make proper diagnoses of arboviruses.