Oropouche virus in Brazil: Assessing the risks and challenges for transfusion medicine

In an era where new pathogens frequently appear and old ones reappear, infectious diseases pose a continuous threat, particularly in cellular therapy and transfusion medicine. As a critical component of healthcare, ensuring the availability and safety of cellular and blood products has become more essential than ever. Over the past five years, the emergence and reemergence of numerous infectious agents, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Monkeypox virus, Zika virus [1], Dengue virus [2], etc., have raised critical questions about their potential transmission through blood transfusion.

The Oropouche virus (OROV) is classified as an arthropod-borne virus belonging to the Peribunyaviridae family, Orthobunyavirus genus, with the primary vector being the midge Culicoides paraensisis [3]. OROV can also be transmitted by species of mosquitoes, including Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus, which significantly amplifies the risk of human spread [3]. As an example, this situation is reminiscent of the urbanization of the Zika virus due to the high incidence of competent vectors such as Aedes aegypti and Aedes albopictus mosquitoes [4].

Since its first isolation in 1955 on the island of Trinidad in the Caribbean, OROV has been identified as the causative agent of numerous outbreaks, still limited, throughout Central and South America. The first OROV outbreak in Brazil occurred in 1961 in Pará [5], reemerging in 2006 in several municipalities within the same state [6]. Several outbreaks have occurred over the past decade, primarily restricted to the Northern region of Brazil, around the Amazon basin [7]. In 2024, Brazil experienced a significant increase in confirmed cases of OROV. By epidemiological week 45 of 2024, 8,754 OROV-positive cases had been identified, compared to 831 in 2023 (Figure 1A) [8]. This rise is partly associated with the decentralization of diagnostic services provided by the Central Public Health Laboratories in each Brazilian state and the consequent enhancement of nationwide molecular testing for the pathogen in samples that tested negative for other arboviruses [9, 10]. Although health policies contributed to this scenario, it is essential to note that OROV is now causing a more extended epidemic and spreading beyond its traditional boundaries (Figure 1B–C), probably due to environmental factors or even influenced by viral evolution and reassortment of the segmented viral genome [11, 12]. Within Brazil, all five macro-regions have detected autochthonous cases, and only five of the 27 states did not report confirmed cases [12, 13]. Many other factors likely contribute to the spread of the disease, such as i) climate change (rising temperatures and altered precipitation patterns), ii) increased global connectivity through human migrations and international trade, iii) deforestation, and iv) urbanization, particularly in areas with inadequate infrastructure [14].

Figure 1. Increasing cases of Oropouche fever over time (2023 –2024).

(A) Barplot indicating the number of cases reported per epidemiological week in 2023 and 2024, up to week 46 (November). (B-C) Maps of Brazil showing Oropouche fever prevalence by federative unit, as indicated by color intensity, in 2023 (B) and 2024 (C). Source: modified from the Oropouche Epidemiological Panel, Brazilian Ministry of Health, 2024 [8].

In July 2024, the first two deaths were attributed to OROV infection [15]. Moreover, OROV has become a crucial area of investigation in pregnant women, particularly after two recent cases of confirmed vertical transmission, which led to fetal death and fatal congenital anomalies, such as microcephaly, ventriculomegaly, and joint malformations [10, 15]. It is pressing to remain vigilant about another transmission route—blood transmission—which could complicate efforts to control the virus and pose a significant public health challenge.

Briefly, the incubation period for OROV is 3 to 8 days, after which patients experience symptoms similar to dengue fever, such as headache, fever, muscle and joint pain, vomiting, and photophobia, with a possibility of hemorrhage and neurological complications [14, 16]. The acute disease usually lasts 2 to 7 days, with peak viraemia on day 2 [14]. Unlike dengue fever, a high percentage of infected individuals have a recurrence of symptoms about one or two weeks after recovery [14, 16]. As with many arboviruses, OROV infection can be asymptomatic [16]. It is challenging to estimate the true prevalence of asymptomatic infections in endemic areas, as these cases often go undetected, and the similarities to symptoms of other arboviruses may lead to incorrect clinical diagnosis.

OROV is found in peripheral blood mononuclear cells (PBMC) [17] and can be isolated from the plasma or serum of infected patients. Alternatively, it has been detected in saliva, urine, and cerebrospinal fluid, pointing to the viral potential for neuroinvasion [18, 19]. As OROV presents a viraemia period [17], there is a theoretical risk that blood from an infected but asymptomatic donor could transmit the virus through transfusion. To date, no cases of OROV-transfusion transmission have been reported, and several questions remain unclear. Addressing this issue requires a comprehensive evaluation of factors such as the duration of viraemia, viral load, the pathogen's survival during blood storage, and the efficacy of blood transfusion transmission, which is essential to determine the actual risk posed to recipients. Nonetheless, transfusion-transmitted infection by OROV could be a significant concern, particularly in endemic arbovirus regions.

The effectiveness of current pathogen inactivation methods (PIM) and leukocyte filtration techniques for arboviruses still needs a validation approach to select PIMs tailored to the specific arbovirus and blood product to ensure maximum safety in transfusion practices [20]. NAT screening techniques and PIMs are crucial for ensuring the safety and efficacy of blood supply management in these endemic arbovirus areas. However, resource constraints often limit access to these technologies in the most affected regions.

Arboviruses pose significant public health threats in Brazil, primarily due to their potential to trigger widespread epidemics with high incidence and prevalence. These diseases not only strain health services through increased demands for surveillance, patient care, and diagnostics but also impose substantial socioeconomic burdens. The economic impact is aggravated by workplace absenteeism, rising healthcare costs, and premature deaths.

Moreover, the constant threat of infectious agents in the blood supply requires ongoing vigilance. This evolving landscape highlights the critical need for continuous research and innovation in transfusion practices to safeguard public health against emerging and re-emerging infectious threats.

DATA AVAILABILITY STATEMENT

The authors declare that the data used for writing this manuscript are fully available.