Oropouche Virus Disease Among U.S. Travelers - United States, 2024.

Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease.

Report of an unusual association of Oropouche Fever with Guillain-Barré syndrome in Cuba, 2024.

Oropouche virus is the aetiological agent of Oropouche fever. At present, this is currently considered one of the most important vector-borne diseases in Latin America. On 27 May 2024, the Ministry of Public Health of Cuba reported the first ever outbreak of Oropouche fever. In this report, we describe three human cases of Oropouche virus infection with symptoms and signs of neurological disease and clinical diagnosis of Guillain-Barré Syndrome. This study offers insights regarding that Oropouche virus is a causal agent of neurological disorders and it could be involved in the etiology of the Guillain-Barré Syndrome.

Oropouche Fever, Cuba, May 2024.

Phylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA. No cases were severe. Virus extension to new areas may increase case numbers and severity.

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.

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.

Vertical Transmission of Oropouche Virus in a Newly Affected Extra-Amazon Region: A Case Study of Fetal Infection and Death in Ceará, Brazil / Transmisión vertical del virus Oropouche en una región extraamazónica recientemente afectada: un estudio de caso de infección y muerte fetal en Ceará, Brasil / Transmissão vertical do vírus Oropouche em uma região extra-amazônica recentemente afetada: um estudo de caso de infecção fetal e morte no Ceará, Brasil

The recent geographic spread of Oropouche virus (OROV), coupled with an increase in cases and the emergence of previously unrecognized severe manifestations, has raised significant public health concerns. We report the case of a 40-year-old family farmer at 31 weeks of gestation who presented with fever, myalgia, and headache. OROV infection was confirmed by RT-qPCR, with other infections ruled out. Initially, maternal and fetal health assessments revealed no complications. However, within a week, the patient noted decreased fetal movements, and ultrasound confirmed fetal demise. Molecular diagnostics identified OROV RNA in multiple fetal tissues, confirming vertical transmission. This case highlights the urgent need to protect pregnant women against viral vectors and include OROV into the differential diagnosis of febrile illnesses. Furthermore, it is critical to further investigate the pathogenic mechanisms of this virus, which may lead to changes in public health policies and clinical guidelines.

La reciente propagación geográfica del virus Oropouche (OROV), junto con un aumento de casos y la aparición de manifestaciones graves no reconocidas previamente, ha suscitado importantes preocupaciones de salud pública. Informamos del caso de un agricultor familiar de 40 años de edad con 31 semanas de gestación que presentó fiebre, mialgia y dolor de cabeza. La infección por OROV se confirmó mediante RT-qPCR, y se descartaron otras infecciones. Inicialmente, las evaluaciones de salud materna y fetal no revelaron complicaciones. Sin embargo, en una semana, la paciente notó una disminución de los movimientos fetales y la ecografía confirmó la muerte fetal. Los diagnósticos moleculares identificaron ARN de OROV en múltiples tejidos fetales, lo que confirmó la transmisión vertical. Este caso destaca la necesidad urgente de proteger a las mujeres embarazadas contra los vectores virales e incluir OROV en el diagnóstico diferencial de enfermedades febriles. Además, es fundamental investigar más a fondo los mecanismos patogénicos de este virus, lo que puede conducir a cambios en las políticas de salud pública y las pautas clínicas.

A recente disseminação geográfica do vírus Oropouche (OROV), juntamente com um aumento de casos e o surgimento de manifestações graves não reconhecidas anteriormente, levantou preocupações significativas de saúde pública. Relatamos o caso de uma agricultora familiar de 40 anos com 31 semanas de gestação que apresentou febre, mialgia e dor de cabeça. A infecção por OROV foi confirmada por RT-qPCR, com outras infecções descartadas. Inicialmente, as avaliações de saúde materna e fetal não revelaram complicações. No entanto, dentro de uma semana, a paciente notou diminuição dos movimentos fetais, e o ultrassom confirmou a morte fetal. O diagnóstico molecular identificou o RNA do OROV em vários tecidos fetais, confirmando a transmissão vertical. Este caso destaca a necessidade urgente de proteger as mulheres grávidas contra vetores virais e incluir o OROV no diagnóstico diferencial de doenças febris. Além disso, é fundamental investigar mais profundamente os mecanismos patogênicos deste vírus, o que pode levar a mudanças nas políticas de saúde pública e diretrizes clínicas.

Oropouche virus infection: What internal medicine physicians should know.

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Reemergence of Oropouche virus between 2023 and 2024 in Brazil.

Background: Oropouche virus (OROV; species Orthobunyavirus oropoucheense) is an arthropod-borne virus that has caused outbreaks of Oropouche fever in Central and South America since the 1950s. This study investigates virological factors contributing to the reemergence of Oropouche fever in Brazil between 2023 and 2024. Methods: In this study, we combined OROV genomic, molecular, and serological data from Brazil from 1 January 2015 to 29 June 2024, along with in vitro and in vivo characterization. Molecular screening data included 93 patients with febrile illness between January 2023 and February 2024 from the Amazonas State. Genomic data comprised two genomic OROV sequences from patients. Serological data were obtained from neutralizing antibody tests comparing the prototype OROV strain BeAn 19991 and the 2024 epidemic strain. Epidemiological data included aggregated cases reported to the Brazilian Ministry of Health from 1 January 2014 to 29 June 2024. Findings: In 2024, autochthonous OROV infections were detected in previously non-endemic areas across all five Brazilian regions. Cases were reported in 19 of 27 federal units, with 83.2% (6,895 of 8,284) of infections in Northern Brazil and a nearly 200-fold increase in incidence compared to reported cases over the last decade. We detected OROV RNA in 10.8% (10 of 93) of patients with febrile illness between December 2023 and May 2024 in Amazonas. We demonstrate that the 2023-2024 epidemic was caused by a novel OROV reassortant that replicated approximately 100-fold higher titers in mammalian cells compared to the prototype strain. The 2023-2024 OROV reassortant displayed plaques earlier than the prototype, produced 1.7 times more plaques, and plaque sizes were 2.5 larger compared to the prototype. Furthermore, serum collected in 2016 from previously OROV-infected individuals showed at least a 32-fold reduction in neutralizing capacity against the reassortment strain compared to the prototype. Interpretation: These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to a better understanding of the 2023-2024 OROV reemergence. The recent increased incidence may be related to a higher replication efficiency of a new reassortant virus that also evades previous immunity.

A reporter Oropouche virus expressing ZsGreen from the M segment enables pathogenesis studies in mice.

Oropouche fever caused by Oropouche virus (OROV) is a significant zoonosis in Central and South America. Despite its public health significance, we lack high-throughput diagnostics, therapeutics, and a comprehensive knowledge of OROV biology. Reporter viruses are valuable tools to rapidly study virus dynamics and develop neutralization and antiviral screening assays. OROV is a tri-segmented bunyavirus, which makes generating a reporter virus challenging, as introducing foreign elements into the viral genome typically affects fitness. We previously demonstrated that the non-structural gene NSm on the OROV medium (M) segment is non-essential for replication in vitro. Taking advantage of this, we have now generated a recombinant OROV expressing fluorescent protein ZsGreen in place of NSm. This reporter OROV is both stable and pathogenic in IFNAR-/- mice and provides a powerful tool for OROV pathogenesis studies and assay development.IMPORTANCEEmerging and reemerging infectious agents such as zoonotic bunyaviruses are of global health concern. Oropouche virus (OROV) causes recurring outbreaks of acute febrile illness in the Central and South American human populations. Biting midges are the primary transmission vectors, whereas sloths and non-human primates are their reservoir hosts. As global temperatures increase, we will likely see an expansion in arthropod-borne pathogens such as OROV. Therefore, developing reagents to study pathogen biology to aid in identifying druggable targets is essential. Here, we demonstrate the feasibility and use of a fluorescent OROV reporter in mice to study viral dynamics and pathogenesis. We show that this reporter OROV maintains characteristics such as growth and pathogenicity similar to the wild-type virus. Using this reporter virus, we can now develop methods to assist OROV studies and establish various high-throughput assays.

Rab27a GTPase and its effector Myosin Va are host factors required for efficient Oropouche virus cell egress.

Oropouche fever, a debilitating illness common in South America, is caused by Oropouche virus (OROV), an arbovirus. OROV belongs to the Peribunyaviridae family, a large group of RNA viruses. Little is known about the biology of Peribunyaviridae in host cells, especially assembly and egress processes. Our research reveals that the small GTPase Rab27a mediates intracellular transport of OROV induced compartments and viral release from infected cells. We show that Rab27a interacts with OROV glycoproteins and colocalizes with OROV during late phases of the infection cycle. Moreover, Rab27a activity is required for OROV trafficking to the cell periphery and efficient release of infectious particles. Consistently, depleting Rab27a's downstream effector, Myosin Va, or inhibiting actin polymerization also hinders OROV compartments targeting to the cell periphery and infectious viral particle egress. These data indicate that OROV hijacks Rab27a activity for intracellular transport and cell externalization. Understanding these crucial mechanisms of OROV's replication cycle may offer potential targets for therapeutic interventions and aid in controlling the spread of Oropouche fever.

Spatiotemporal Epidemiology of Oropouche Fever, Brazil, 2015-2024.

We assessed the spatiotemporal dynamics of Oropouche fever in Brazil during 2015-2024. We found the number of cases substantially increased during that period, particularly in the Amazon region. Our findings underscore the need for improved surveillance and public health measures in response to the disease's potential spread beyond endemic areas.