Within the framework of WEEV case notification in Córdoba, Argentina, the Hemovigilance System of the Fundación Banco Central de Sangre (FBCS) developed intervention strategies tailored to the regional epidemiologic context and the operational characteristics of the blood bank. Those strategies, aimed at safeguarding transfusion safety, included the creation of epidemiologic maps to geolocate infections, the establishment of blood donor selection criteria, and the selection of plasma samples from donors residing in areas affected by the virus for the specific detection of WEEV RNA by NAT.

We implemented the strategies and interventions at the FBCS, a reference blood bank in Córdoba, the second most populous province in Argentina. The FBCS coordinates and centralizes the activities of multiple blood transfusion services operating across the province’s 165,321-km² territory. Approximately 50% of all blood units collected throughout Córdoba undergo serologic and molecular pretransfusion screening at FBCS. Consequently, the donor population represented in this blood bank is not confined to a specific locality but covers a broad geographic area in the central region of the country.

After the report of a human case of WEEV infection in Córdoba (January 26, 2024), through epidemiologic maps, we identified areas of suspected WEEV circulation (hotspots). We implemented interventions in the affected areas from February 5, 2024, through the first week of April 2024 (epidemiologic weeks 6–14). The staff of the mobile blood collection teams scheduled to operate in those areas, as well as the personnel at fixed blood collection sites located within the identified hotspots, were instructed to conduct donor selection in accordance with the procedures we described. In addition, we used updated donor information materials to reinforce the importance of reporting postdonation reaction.

During the intervention period, a total of 4,048 persons (56% male, 44% female; mean age 38 years, interquartile range [IQR] 28–52 years) donated blood at fixed donation centers and external collection sites. Of those donors, 637 (49% male, 51% female; mean age 38 years, IQR 32–47 years) resided in areas identified by our mapping system as having suspected WEEV circulation. Most locations identified as hotspots were in rural areas where many residents, including altruistic repeat blood donors, live in close contact with horses and maintain close domestic contact with them. Eligible donors identified as potentially exposed to WEEV on the basis of our additional selection criteria were temporarily deferred from donation. For example, applying our selection criteria enabled us to identify persons otherwise eligible to donate blood as close contacts of someone who had died from WEEV infection.

We processed all samples from donors identified as living in hotspots by alphavirus NAT; we identified 1 viremic donor. We deposited the sequence obtained from PCR product into GenBank (accession no. PV641588). The phylogenetic analysis revealed that sequence clustered within the lineage associated with WEEV isolates detected during the 2023–2024 outbreak in South America (Figure). Specifically, we observed the highest genetic similarity to sequences reported from Argentina and Uruguay during that period, suggesting a close epidemiologic relationship with the viral strains responsible for that regional outbreak. In the tree, the sequence, PV641588 ARG CBA 354546 (Argentina, 2024), clustered within the recently proposed C sublineage (11); we found no evidence of introduction from North America or other continents in our analysis. Because the sequence is genetically very close to circulating equine and mosquito isolates, our findings are consistent with a human infection occurring in the context of the equine–mosquito enzootic/epizootic cycle characteristic of the C sublineage in South America.

Among emerging viruses with public health impact that threaten transfusion safety, arboviruses are a major concern because of their ability to cause asymptomatic viremia, their rapid geographic expansion, and the absence of systematic pretransfusion screening tests. In response to the WEEV outbreak in Argentina, we identified the need to implement specific interventions to assess potential risks to transfusion safety.

Collaboration with community promoters proved valuable during the WEEV outbreak, providing localized epidemiologic insights not captured in official public health reports. Information gathered from community promoters and local blood drive organizers enabled real-time situational awareness and enabled the FBCS to identify areas of suspected viral circulation. In addition, information reported by potential donors during predonation screening, particularly regarding suspected or probable cases within their communities, contributed valuable on-the-ground data that helped build a more complete picture of WEEV circulation across the province. That combined flow of community-based and donor-reported data contributed to shaping adaptive measures, guiding risk assessment, and refining donor selection criteria. Overall, our findings suggest that community engagement can enhance transfusion safety during outbreaks and underscore the importance of flexible, locally informed strategies to protect the blood supply in the face of emerging infectious threats.

During WEEV reemergence, the rapid adaptation of donor selection criteria by our blood banks was important to safeguard the blood supply. Standard eligibility assessments may not adequately capture evolving exposure risks. Incorporating targeted questions enabled a more rigorous evaluation of donor risk during those critical periods. Of note, the development of the questions was strengthened by information provided by community promoters, whose knowledge of local idiosyncrasies, customs, and daily practices offered valuable insights into potential exposures. Thus, integrating context-specific data into standard donor eligibility screening supported the implementation of appropriate deferral measures to prevent TTIs. Moreover, the 30-day donor deferral period reflected a risk-based approach tailored to a complex epidemiologic context, characterized by the concurrent circulation of WEEV and a large dengue outbreak in 2024. Although longer deferral periods could further reduce the theoretical risk for transfusion transmission, extending deferral beyond 30 days would likely compromise the availability of critical blood components in a system already under strain. Those findings underscore the importance of adaptive context-informed donor selection strategies to maintain both transfusion safety and blood supply resilience during emerging infectious threats

Our study revealed through NAT that an asymptomatic viremic donor might pose a risk for TTI despite implementation of targeted questions to minimize transfusion risk. That finding is consistent with the high frequency of asymptomatic infections associated with WEEV and highlights an inherent limitation of symptom-based and exposure-based donor screening; namely, a residual risk. We found no evidence of inaccurate disclosure during donor history assessment; rather, the most plausible explanation is that at the time of donation the donor was in the asymptomatic viremic phase, which cannot be identified through standard predonation screening. Therefore, in viral infection scenarios involving a high proportion of asymptomatic persons, molecular screening should complement targeted donor selection strategies to meaningfully reduce residual TTI risk. In a previous hemovigilance study (21), we proposed a cost-efficient molecular screening strategy for arboviruses in blood donors based on a NAT assay configured with universal degenerate primer pairs targeting conserved genomic regions, which could detect a broad range of viruses in a single reaction. That generic screening platform could enable a rapid response to emerging threats such as WEEV. Beyond transfusion safety, molecular screening of blood donors also can function as a valuable surveillance tool for uncovering silent viral circulation. Because routine surveillance systems rely on clinical reporting of symptomatic cases, asymptomatic infections often remain undetected. In that context, monitoring an asymptomatic population such as blood donors can fill an important surveillance gap by helping to identify otherwise unrecognized transmission and complementing traditional surveillance systems, thereby supporting the detection of emerging threats and the identification of transmission patterns and hotspots (9,21).

Molecular screening of blood donors not only reveals WEEV circulation among eligible donors but also enables characterization of human-derived viral strains. The isolate we identified, PV641588, did not form a distinct lineage; instead, it clustered with contemporary South America strains associated with the mosquito–equine transmission cycle (2023–2024) (10–12), supporting shared transmission dynamics across hosts. Phylogenetic analysis showed that PV641588 belongs to the recently described C sublineage (11), which has circulated in South America for decades. The clustering of recent isolates from Argentina, Uruguay, and Brazil is consistent with a possible regional intensification of viral circulation. The placement of PV641588 within that group supports the hypothesis that the human infection occurred in the context of active enzootic transmission, rather than representing a divergent lineage.

Our findings suggest that responsive, community-informed strategies can strengthen transfusion safety while helping to maintain the continuity and resilience of the blood supply during periods of epidemiologic uncertainty. They also reinforce the value of molecular screening in blood banks as a surveillance tool capable of detecting silent viral circulation that traditional clinical reporting systems may miss. Together, our results highlight the role of blood donors as sentinels for emerging arboviral threats and support integrating molecular surveillance into routine blood bank practices to strengthen public health preparedness.