The national burden from O'nyong'nyong and chikungunya viruses in Cameroon.

O'nyong-nyong (ONNV) and chikungunya (CHIKV) are arboviruses that have been identified nearly throughout Africa. However, the disease burden from the viruses has been rarely quantified as surveillance systems are poorly equipped to identify cases. Here, we tested 6,324 serum samples collected as part of the Yellow Fever testing program between 2010 and 2023 in individuals of all ages from all the health districts of Cameroon. We used a novel multiplex assay that incorporated antigens from three alphaviruses (ONNV, CHIKV and MAYV) and mathematical models that explicitly consider cross-reactivity to reconstruct individual and population infection histories for each virus. We found that despite no cases reported in Cameroon, ONNV has circulated endemically across the country for decades with an average of 332,000 annual infections and 8 million individuals with a history of infection. By contrast, we found evidence of only sporadic CHIKV outbreaks, with an estimated prevalence of 1.7%. Models that did not explicitly consider cross-reactivity between the alphaviruses lead to incorrect conclusions about the circulation of the viruses. This work highlights the need for systematic efforts to identify ONNV incident cases and the development of a vaccine development investment case against this neglected pathogen.