A diagnostic void in the Congo Basin: proposing a zoonotic orthopoxvirus as the cause of a hemorrhagic fever outbreak and a call for equitable health security

Background In February 2025, a fatal outbreak of a hemorrhagic fever-like illness emerged in the Basankusu Health Zone of the Democratic Republic of Congo (DRC), a region where the burdens of poverty and infectious disease intersect. Initial field diagnostics for common filoviruses like Ebola and Marburg returned negative, creating a critical diagnostic void and confronting local health systems with a potential “Disease X.” This opinion piece analyzes the outbreak’s unique clinical and ecological context to advance a specific, actionable hypothesis. Main body We argue that the presenting clinical syndrome, particularly the unusual combination of hemorrhagic signs with intractable hiccups and dysphagia, is highly consistent with a fulminant zoonotic orthopoxvirus infection. We hypothesize that this spillover event is directly linked to the socio-ecological pressures of poverty, including reliance on bushmeat for protein and accelerated deforestation for subsistence agriculture and charcoal production, which increase human-wildlife contact. Framing the outbreak through this lens shifts the public health paradigm from confronting a complete unknown to managing a new variant of a known threat. This perspective underscores that the poverty-driven exploitation of ecosystems is a primary engine of novel epidemics. Conclusions The definitive etiology of the Basankusu outbreak remains unresolved, but the clinical and ecological evidence points toward a potential zoonotic origin consistent with known patterns of pathogen emergence in the Congo Basin. In a setting constrained by limited diagnostic capacity, such evidence-informed approach provides a pragmatic framework for immediate public health action—guiding the deployment of targeted diagnostics (pan-poxvirus PCR), therapeutics (tecovirimat), and vaccines (MVA-BN). Ultimately, preventing future outbreaks of diseases of poverty requires a global commitment to investing in local diagnostic capacity, sustainable development, and equitable health security within high-risk endemic regions like the Congo Basin. Graphic abstract